Diponziano v. Secretary of Health and Human Services

In the United States Court of Federal Claims

OFFICE OF SPECIAL MASTERS

Filed: February 11, 2025

* * * * * * * * * * ** *

DORIS DIPONZIANO, *

*

Petitioner, * No. 17-1130V

*

v. * Special Master Gowen

*

SECRETARY OF HEALTH * Entitlement; Pneumococcal

AND HUMAN SERVICES, * Conjugate Vaccination (“Prevnar”);

* Guillain-Barré Syndrome (“GBS”).

Respondent. *

* * * * * * * * * * * * *

Irene McLafferty, Mess and Associates, P.C., Philadelphia, PA, for petitioner.

Lynn Christina Schlie, U.S. Department of Justice, Washington, D.C., for respondent.

RULING ON ENTITLMENT 1

On August 22, 2017, Doris DiPonziano (“petitioner”) filed a petition for compensation

under the National Vaccine Injury Compensation Program. 2 Petitioner filed an amended petition

on August 24, 2017, alleging that the pneumococcal conjugate vaccine (“Prevnar 13” or

“Prevnar”) she received on July 11, 2016, was the cause-in-fact of her Guillain-Barre Syndrome

(“GBS”). Petition (ECF No. 1); Amended Petition (ECF No. 9).

1

In accordance with the E-Government Act of 2002, 44 U.S.C. § 3501 (2012), because this opinion contains a

reasoned explanation for the action in this case, this opinion will be posted on the website of the United States

Court of Federal Claims. This means the opinion will be available to anyone with access to the internet. As

provided by 42 U.S.C. § 300aa-12(d)(4)B), however, the parties may object to the published Decision’s inclusion of

certain kinds of confidential information. Specifically, under Vaccine Rule 18(b), each party has 14 days within

which to request redaction “of any information furnished by that party: (1) that is a trade secret or commercial or

financial in substance and is privileged or confidential; or (2) that includes medical files or similar files, the

disclosure of which would constitute a clearly unwarranted invasion of privacy.” Vaccine Rule 18(b). If neither

party files a motion for redaction within 14 days, the entire opinion will be posted on the website and available

to the public in its current form. Id.

2

The National Vaccine Injury Compensation Program is set forth in Part 2 of the National Childhood Vaccine

Injury Act of 1986, Pub. L. No. 99-660, 100 Stat. 3755, codified as amended, 42 U.S.C. §§ 300aa-10 to 34 (2012)

(hereinafter “Vaccine Act” or “the Act”). Hereinafter, individual section references will be to 42 U.S.C. § 300aa of

the Act.

1

Based on a full review of the evidence and testimony presented, I find that petitioner has

established by a preponderance of the evidence that the Prevnar 13 vaccine caused her GBS, and

therefore she is entitled to compensation. 3

I. Procedural History

Petitioner filed a petition for compensation on August 22, 2017 and an amended petition

on August 24, 2017, alleging that the Prevnar 13 vaccine she received on July 11, 2016, caused

her to suffer GBS. Petition; Amended Petition. The amended petition was accompanied by

medical records. Petitioner’s Exhibits (“Pet’r Ex.”) 1-6 (ECF No. 9). On April 26, 2018,

respondent filed a status report stating that he intended to defend against the claim and that

settlement discussions were not appropriate. Respondent’s (“Resp’t”) Status Report (“Rept.”)

(ECF No. 18).

On June 12, 2018, respondent filed his Rule 4(c) report, recommending against

compensation in this case. Resp’t Rept. at 1 (ECF No. 21). Specifically, respondent stated that

the medical records fail to establish a “more likely than not causal connection between

petitioner’s vaccination and the onset of her GBS,” and that, while some of her treating

physicians noted the temporal relationship, “none provided a causal theory beyond simply an

alleged temporal association.” Id. at 7.

Thereafter, petitioner filed an expert report from Robert Hyzy, M.D., 4 and respondent

filed an expert report from Brian Callaghan, M.D., M.S. 5 Pet’r Ex. 9 (ECF No. 33); Resp’t Ex. A

3

Pursuant to Section 300aa-13(a)(1), in order to reach my conclusion, I have considered the entire record including

all of the medical records, statements, expert reports, and medical literature submitted by the parties. This opinion

discusses the elements of the record I found most relevant to the outcome.

4

Dr. Hyzy graduated from Kenyon College with a Bachelor of Arts Degree in Biology and Psychology in 1978.

Pet’r Ex. 9.1 at 1. He graduated from New York University School of Medicine in 1982, followed by an internship

in Internal Medicine from the University of Michigan in 1983. Id. He completed his residency in Internal Medicine

at the University of Michigan in 1985. Id. Dr. Hyzy completed a fellowship in Pulmonary and Critical care Medicine

also at the University of Michigan in 1989. Id. He is board certified in in Internal Medicine, Pulmonary Medicine,

and Critical Care Medicine. Id. He was an instructor, lecturer, Clinical Assistant Professor in Internal Medicine,

Associate Professor of Internal Medicine, and Professor of Internal Medicine in the University of Michigan Health

System. Id. at 1-2. Dr. Hyzy has focused his research on pulmonology, internal medicine, and critical care. See Pet’r

Ex. 9.1. Dr. Hyzy did not testify at the entitlement hearing.

5

Dr. Callaghan graduated from the University of Michigan with a Bachelor of Science degree in 1996. Resp. Ex. B

at 1. He graduated from the University of Pennsylvania Medical Center with a medical degree in 2004. Id. He

remained at the University of Pennsylvania Medical Center for an internship in preliminary medicine from 2004 –

2005 and a residency in neurology from 2005 – 2008. Id. Afterwards, Dr. Callaghan completed a fellowship in

neuromuscular medicine and a master’s degree in clinical research design and statistical analysis at the University of

Michigan Medical School. Id. In 2009, he was hired onto the Michigan faculty, where he is currently an associate

professor in neurology. Id. Dr. Callaghan is also a clinical neurologist and director of the ALS Clinic at the Veterans

Affairs Ann Arbor Health System. Id. at 1-2. He is board-certified in psychiatry and neurology as well as

electrodiagnostic medicine. Id. Dr. Callaghan stated that his primary interest is in patients with neuropathy and

neuralgic amyotrophy. Resp. Ex. A at 3. While Dr. Callaghan did not state what number or proportion of his patients

have these disorders, his curriculum vitae reflects that he teaches, conducts research, publishes, and serves as an

2

(ECF No. 31). On April 11, 2019, I held a Rule 5 Status Conference, where I indicated that

petitioner needed to provide further evidence to address the three prongs in Althen. Scheduling

Order, Apr. 12, 2019 (ECF No. 37); Althen v. Sec’y of Health & Human Servs., 418 F.3d 1274,

1278 (Fed. Cir. 2005).

On July 26, 2019, petitioner filed additional expert reports from Robert Knobler, M.D.,

PhD 6 and Matthew Lee, M.D., RPh, M.S. 7 Pet’r Ex. 11; Pet’r Ex. 12 (ECF No. 43). On October

9, 2019, respondent filed a supplemental expert report from Dr. Callaghan. Resp’t Ex. C (ECF

No. 53). On October 28, 2019, respondent filed an expert report from You-Wen He, M.D., PhD. 8

Resp’t Ex. D (ECF No. 55). After a second Rule 5 Conference and unsuccessful settlement

negotiations, an entitlement hearing was set, and the parties filed pre-hearing briefs. Scheduling

Order, Nov. 27, 2019 (ECF No. 56); Resp’t Status Rept., May 12, 2020 (ECF No. 72); Hearing

editor for numerous peer-reviewed journals focusing on peripheral neuropathy. See generally Resp. Ex. A. Dr.

Callaghan was admitted as an expert in the subjects of neurology, and electrodiagnostic medicine. Tr. 319.

6

Dr. Knobler graduated from the City College of New York with a BS in Biology in 1969. Pet’r Ex. 12 at 1. He

graduated from the State University of New York with an M.D. and a PhD in Anatomy in 1975. Id. Dr. Knobler

completed his residency in Neurology at Kings County Hospital Center in 1979. Id. He was a postdoctoral research

fellow in the Department of Immunopathology at the Scripps Clinic and Research Foundation from 1979-1982, and

was a clinical coordinator and co-director in the Multiple Sclerosis Research Center at Scripps Clinic and Research

Foundation. Id. He has been an assistant professor, associate professor, adjunct professor, and professor at Thomas

Jefferson University, Department of Neurology, from 1984 to 2002. Id. at 2. He was the Director of the Multiple

Sclerosis Comprehensive Clinical Center at Thomas Jefferson University Hospital from 1996-1998. Id. His research

area includes immunology and multiple sclerosis. See Pet’r Ex. 12. He has an active medical license in Pennsylvania

and is a reviewer for a variety of journals in the fields of Neurology, Immunology, and Multiple Sclerosis. Id. at 3-5.

Dr. Knobler was admitted as an expert in the field of neurology with a background in immunology and virology. Tr.

120.

7

Dr. Lee graduated from Virginia Commonwealth University with a BS in Chemistry in 1992. Pet’r Ex. 11 at 2. He

graduated from the Medical College of Virginia with a Bachelor of Science in Pharmacy in 1995, and a Master of

Science in Pharmacology and Toxicology in 1999. Id. at 2. He received his M.D. from Virginia Commonwealth

School of Medicine in 2004 and completed a post-doctoral internship in internal medicine in 2005. Id. at 2-3. He has

been licensed to practice medicine and surgery in Virginia since 2005 and has been licensed to practice pharmacy in

Virginia since 1995. Id. at 3. In 2016, he was appointed a consultant to the FDA advisory committee for

pharmaceutical science and clinical pharmacology. Id. at 4. He is currently a primary care physician, a pharmacist,

medical examiner, and veterans’ evaluation services provider. Id. at 1. Dr. Lee was admitted as an expert in the field

of pharmacology, internal medicine, and toxicology. Tr. 76.

8

Dr. He graduated from the Fourth Military Medical University in Xian, China with an M.D. in 1986. Resp. Ex. E at

1. He Graduated from the Institute of Microbiology and Epidemiology from the Academy of Military Medical

Science in Beijing in 1989. Id. He graduated from the Department of Microbiology & Immunology from the

University of Miami School of Medicine in 1996. Id. Afterwards he was a Senior Fellow at the Howard Hughes

Medical Institute in the Department of Immunology at the University of Washington. Id. He has been a Professor of

Immunology in the Department of Immunology at Duke University Medical Center since 2000. Id. His research

areas include innate and adaptive viral and bacterial immunity. Id. at 3-15. He has directed research on human

immune responses to viral infections including influenza, HIV, HBV, and HCV. Id. He has been the Director of

Immunology of Human Diseases at Duke University for the past five years and is the current Co-Principal

Investigator for four clinical trials focusing on cancer immunotherapy. Id. at 3. He has served as a reviewer for over

20 different scientific journals and has published extensively in immunology. Id. at 9-17. Dr. He was admitted as an

expert in the field of immunology. Tr. 227.

3

Order (ECF No. 77); Pet’r Pre-Hearing Brief (ECF No. 82); Resp’t Pre-Hearing Brief (ECF No

83); Pet’r Reply to Resp’t Pre-Hearing Brief (ECF No. 107).

An entitlement hearing was held on September 16 and 17, 2021. At the conclusion of Dr.

Knobler’s testimony on September 17, 2021, respondent requested a continuance to review the

transcript and have an opportunity to prepare a response to Dr. Knobler’s testimony. Tr. 184. I

granted respondent’s request and respondent filed supplemental expert reports from Drs.

Callaghan and He. Id. at 184-85; Resp’t Ex. F (ECF No. 100); Resp’t Ex. G (ECF No. 100). The

hearing concluded on October 21, 2021, and the parties thereafter filed post-hearing briefs. Pet’r

Post-Hearing Brief (ECF No. 105); Resp’t Post-Hearing Brief (ECF No. 106); Pet’r Post-Hearing

Reply (ECF No. 107).

The matter is now ripe for adjudication.

II. Evidence Submitted

a. Summary of Petitioner’s Medical History

Prior to petitioner’s vaccination and GBS onset, petitioner and her husband shared the

household responsibilities, doing “a lot of the shopping and running errands.” Id. Both were

retired by this point, and both could drive. Id. at 8, 15. Petitioner’s brother-in-law, Mr. Tony

Perez, testified that petitioner and her sister “got together often” for different activities such as

“flower shows, different trips, shopping trips and things of that nature.” Id. at 8. Petitioner was a

“very healthy person” and “had a lot of energy.” Id. Petitioner’s husband, Mr. Carl DiPonziano

noted that, prior to the vaccination, he and petitioner would shop together, visit with friends, and

“do the normal things that people do.” Id. at 30. Petitioner did the cleaning, laundry, and cooking

in the house. Id. She was “very active” at this time, “she walked very fast,” and was “just very

busy all the time.” Id. at 30.

On July 11, 2016, petitioner, a 79-year-old female, presented to Dr. Mary Monari-Sparks

for a follow up for continued complaints of fatigue, two episodes of chest pain with exertion, and

a skin lesion that was slow to resolve beneath her left breast. Pet’r Ex. 2 at 7. Petitioner’s

medical history at this time included, in part, gastroesophageal reflux disease, trochanteric

bursitis, primary localized osteoarthritis of the lower leg, degenerative disc disease, shoulder

joint pain, midline low back pain, and left leg pain. Id. at 8. Significantly for the issues in this

case she was recorded as suffering from allergic rhinitis since at least 2015. Id. Petitioner noted

at the hearing that she had “general” health issues and took Synthroid for hypothyroidism and

Nexium for acid reflux. Tr. 50-51. Petitioner’s husband, Carl DiPonziano testified that petitioner

had allergies with symptoms including itching eyes and “running of the eyes.” Id. at 30. Mr.

Perez also noted that petitioner had allergies with “tearing of her eyes and itchy eyes from time

to time. She would have some nasal discharge. She would blow her nose with some frequency,

often going through several different boxes of tissues. Most of it seemed to be seasonal…[in the]

spring, summertime.” Id. at 9.

4

Petitioner’s exam at the July 11, 2016 appointment was unremarkable aside from the

lesion and rash beneath her breast and fatigue. Pet’r Ex. 2 at 13. Diagnoses at this appointment

included precordial pain, unspecified hypothyroidism, right thumb pain, rash, and skin lesion. Id.

at 15. She was referred to cardiology for the precordial pain and to dermatology for the skin

issues. Petitioner also received the Prevnar 13 vaccine at this appointment. Id.

About one day after the vaccination, petitioner’s arm became sore, “was very red,” and

“looked kind of crusty” at the injection site. Tr. 49. Petitioner’s husband, Carl DiPonziano noted

that there was swelling on the left arm that was about “two inches long by an inch wide” with

redness. Id. at 32-33. A few days later, petitioner and her sister took a trip to Atlantic City, and

petitioner recalled being concerned about her sore arm. Id. at 52. Mr. DiPonziano recalled that

petitioner “was fine” when she left for this trip and was not coughing or otherwise sick. Id. at 33.

Mr. Perez was unaware of any other symptoms, including fever or other issues, aside from

swelling at the injection site and noted that that if petitioner “wasn’t feeling well, she wouldn’t

have gone down to the shore, and [her husband] certainly wouldn’t have let her go down to the

shore.” Id. at 9.

On the evening of July 22, 2016, petitioner was not “feeling good” and had “tingling in

her hands and feet.” Id. at 52-53. Early the next morning she “was not able to move very well”

and her husband called 911. Id. Petitioner “did not feel as though she was sick in any way…even

[with] a cold.” Id. at 54. Her only symptoms at this point were “tingling and not feeling like

[her]self.” Id. Mr. DiPonziano testified that petitioner complained that she felt “kind of weird,”

noting tingling in her fingers and toes that “gradually got stronger.” She was awake by 5:00 the

next morning and could barely walk, requiring Mr. DiPonziano’s assistance to the bathroom. Id.

at 34. Mr. DiPonziano called 911, and petitioner was taken to the ED and transferred to the ICU

at Cooper University Hospital. Id. at 35-36. Mr. Perez added more details about the onset of

petitioner’s symptoms during his testimony at the hearing, noting that petitioner did not complain

of feeling unwell until July 22, 2016, the night before she was admitted to Cooper University

Hospital. Id. At that point, she “was complaining that she wasn’t feeling herself and she felt

some numbness in her fingers and toes. By…early the next morning…she was hardly able to

move.” Id. at 10-11. Petitioner’s husband called 911, and Mr. Perez and his wife met them at the

Cooper University Hospital ED. Id. at 11.

i. Admission to Cooper University Hospital

On July 23, 2016, twelve days after vaccination, petitioner presented to the Cooper

University Hospital Emergency Department (“ED”) complaining of numbness and tingling in her

hands and feet starting at about 10:00 p.m. the previous night “with progressive severe

weakness.” Pet’r Ex. 3 at 57, 60. Petitioner reported that she “felt weakness in her arms and legs

bilaterally and ‘could not walk’” when she woke up. Id. She also reported a red rash to the left

upper arm over the past week that resolved. Id. at 56-57. The ED physician noted that petitioner

was positive for recent upper respiratory infection (“URI”) symptoms for four days, and that she

recently received the pneumovax vaccine. Id. Mr. Perez testified that, during this time, “it was

obvious that…[petitioner] was becoming more and more paralyzed. Tr. at 12.

5

On physical examination, petitioner had 2/5 strength in the bilateral upper extremities and

3/5 strength in the bilateral lower extremities. Pet’r Ex. 3 at 59. Petitioner could not hold her

arms in the air but had “equal and strong grips” bilaterally. Id. at 56. She was unable to walk

secondary to weakness. Id. at 59. Neurological symptoms included tingling, sensory change, and

weakness, but the physical examination noted “no sensory deficit.” Id. at 59. Petitioner’s

respiratory symptoms included a cough, but her pulmonary effort and breath sounds were

normal. She had “no respiratory distress…no wheezes…no rales…[and] no tenderness.” The

examination of her mouth and throat recorded: “Uvula is midline, oropharynx is clear and moist

and mucous membranes are normal. No oropharyngeal exudate, posterior oropharyngeal

erythema or tonsillar abscesses.” Id. at 57-58 The ED physician’s assessment noted that

petitioner was “a 79 [year old] female presenting with one day of acute onset bilateral weakness

and paresthesias in [the upper extremity] and [lower extremity] with antecedent URI

[symptoms].” Id. The differential diagnosis included “concern for” Guillain Barre Syndrome

“given bilateral weakness and recent URI/vaccine.” Id. The plan included lab work, head CT,

lumbar puncture, and a neurology consultation. Id.

The ED physician performed another physical examination about two hours later due to

petitioner’s “progressive paralysis.” Id. at 63. By this time, petitioner was positive for “mild

[bilateral expiratory] wheeze” in the lungs. Id. at 62. Her neurological examination revealed 3/5

strength in the bilateral upper extremities and 4/5 strength in the bilateral lower extremities. Id.

The physician was “unable to elicit patellar or ankle jerk reflexes,” and petitioner was positive

for bilateral pronator drift. Id. at 62. The “leading diagnosis” at this point was GBS given “the

lack of bulbar” symptoms. Id. at 63. Immediate interventions included “imaging, emergent

consultation with neurology and critical care, [and] intravenous immunoglobulin (“IVIG”)

initiation.” Id.

About five hours later, petitioner was reassessed and had “persistent and worsening

weakness bilaterally.” Id. at 64. Petitioner’s labs and head CT showed no abnormalities. Id. at

65. A lumbar puncture was performed and “showed no protein in fluid which would be

consistent with GBS,” if the disease was in the early stages. Id. The plan was to admit petitioner

to the ICU with neurology to follow her, and petitioner was placed on a nasal cannula due to

oxygen desaturation. Id. at 65-66.

The Critical Care history and physical noted that petitioner had a history of

hypothyroidism and multiple allergies and presented “with acute rapidly progressive dysesthesia

and paresis.” Id. at 71. Petitioner reported tingling in her fingers followed by her toes the night

before she presented to the ED, “rapidly followed by her inability to walk.” Id. Petitioner denied

“bowel/bladder incontinence, difficulty breathing, dizziness, [and] palpitations.” Id. She also

reported receiving “a pneumonia vaccine around 10 days [ago] which was followed by

erythematous rash in her arm/shoulder region” at the injection site, and “URI symptoms for the

past five days,” including hoarseness over the past three to four days. Id. at 71, 77. The

pulmonary exam was “clear to auscultation bilaterally” with “no rales or wheezes.” Id.at 73.

Assessment of the skin showed an “erythematous rash on [the] right shoulder” measuring 4 by 4

centimeters. Id. The neurologic exam revealed 2/3 strength in the right upper extremity, 3/3

strength in the left upper extremity, and 3/5 strength in the bilateral lower extremities.” Id. at 74.

Areflexia was present in both legs. Id. The Critical Care physician’s impression was concern “for

6

GBS due to symmetrical involvement,” and noted that “possible triggers include pneumonia

vaccine, preceding URI.” Id. The plan included a five-day course of IVIG and a low threshold

for intubation in case of respiratory decompensation. Id.

The initial neurology consult on July 23, 2016, included a detailed timeline of the onset

of petitioner’s symptoms, noting that

Last evening, around 6:00 p.m., [petitioner] began to experience numbness in her

distal fingers. Numbness involved all five fingers in her bilateral hands. Later that

evening the numbness was also present in her distal toes, again all five toes

bilaterally. She reports around 9:00 p.m. she started to experience some

generalized weakness. She was able to walk but felt as though she needed to hold

on to chairs/the wall in order to feel stable. She went to bed but was having

difficulty sleeping secondary to left arm and right leg pain. She awoke from bed

in the middle of the night and walked to her recliner in her living room. Around

5:00 a.m. this morning she awoke and could not get out of her recliner. She called

her husband and they called EMS and [she] was brought to the hospital. She

reports her weakness is worsening over the few hours that she has been here.

Initially she was able to stand and raise her arms and legs and now she is unable

to raise her arms, and can only raise her legs slightly…She recently received the

pneumovax on the 19th of this month. She reported a slight, confluent red rash on

her left arm after the injection that has since resolved. She reports on Tuesday of

this week she began to have a URI. She has had a dry cough, rhinorrhea, and post

nasal drip. 9

Id. at 108.

The motor examination performed during the neurology consult revealed 1/5 strength in

the proximal right arm, 2/5 strength in the proximal left arm, 3/5 strength the distal right and left

arms, 3/5 strength in the bilateral proximal lower extremities, and 4/5 strength in the bilateral

distal lower extremities. Id. at 112. Petitioner’s sensation was intact to light touch, pinprick, and

vibration diffusely including the distal fingers and toes. Id. Her reflexes were diffusely absent,

and the Babinski reflex was negative bilaterally. Id. Petitioner was unable to perform the finger

to nose or heel to shin coordination tests due to weakness. Id. Her fine motor movement was

intact, and rapid alternating movement was slow. Id. She could give a “very weak but symmetric

grip and wiggle toes but [was] unable to move [her] arms or legs against gravity.” Id. at 115.

Neurology recommended admitting petitioner to the ICU for “close monitoring of

hemodynamics and respiratory status,” and IVIG treatment for five days. Id.

Petitioner received her first dose of IVIG on July 23, 2016, and completed IVIG

treatment on July 27, 2016. See id. at 282, 301. A neurology consultation on July 27th noted “no

significant improvement in [petitioner’s] extremity weakness.” Id. at 278. At the end of her IVIG

9

Given the reference to days of the week in this neurology consult from July 23, 2016 it should be noted that the

vaccine was actually administered on July 11, 2016. The onset of symptoms was Friday evening July 22, 2016 and

the reference to the onset of URI symptoms on Tuesday would have been July 19, 2016 or three days before the

onset of GBS symptoms.

7

treatment, petitioner was transferred from the ICU to the intermediate care unit but was

transferred back to the ICU the following day due to increasing oxygen requirements. Id. at 268,

279. By July 29, 2016, petitioner’s strength was 1-2/5 in all extremities, and she began taking

gabapentin for neuropathic pain. Id. at 258-59. On August 2, 2016 petitioner was intubated and

sedated due to respiratory distress. Id. at 123, 216. After failing an extubation attempt, she was

re-intubated on August 7, 2016. Id. at 118. A tracheostomy procedure was performed on August

10, 2016. Id. at 116. Petitioner remained intubated throughout the rest of her hospitalization and

was transferred to a rehabilitation hospital on August 13, 2016. Id. at 67. Her hospital course was

further complicated by MSSA bacteremia and multifocal pneumonia. Id. at 67, 86, 207; Pet’r Ex

4 at 23. At the time of her discharge, petitioner’s diagnoses included acute respiratory failure

with hypoxia, on mechanically assisted ventilation, GBS, and unspecified hypothyroidism. Pet’r

Ex. 3 at 68.

ii. Admissions to Long Term Care Facilities

On August 13, 2016, petitioner was transferred to Lourdes Specialty Hospital for

ventilator weaning, where she stayed until September 9, 2016. Pet’r Ex. 4 at 17, 23, 187.

Diagnoses upon admission included “ventilator-dependent respiratory failure/chronic respiratory

failure, Guillain-Barre syndrome with respiratory compromise,” pneumonia, and “methicillin-

sensitive staphylococcus aures bacteremia.” Id. at 25. Mr. Perez noted that, at the time of her

transfer to Lourdes, petitioner was unable to walk. Tr. 14. She was weaned off mechanical

ventilation after the pneumonia and bacteremia resolved. Pet’r Ex. 4 at 16-18. During this

admission, petitioner had physical therapy (“PT”), occupational therapy (“OT”), and speech

therapy. Id. at 284-319. She eventually regained the ability to feed herself. Tr. 14. At the time of

her discharge, petitioner had been “successfully weaned from mechanical ventilation” and was

decannulated. Pet’r Ex. 4 at 16. Petitioner was transferred to a rehabilitation facility on

September 9, 2016. Id. at 16-17.

Petitioner was admitted to Marlton Rehabilitation Hospital on September 9, 2016, where

she continued to have generalized weakness. Pet’r Ex. 5 at 41. Upon her admission, the right

upper extremity had 3/5 strength, and the left upper extremity had 4/5 strength. Id. The lower

extremity strength was “much decreased compared to the upper extremities,” with petitioner

demonstrating 1/5 strength in the right lower extremity and 2/5 strength in the left. Id. Petitioner

also had bilateral foot drop. Id. During this admission, petitioner received PT, OT, and speech

therapy “for progressive ambulation, [activities of daily living] training, strengthening and

general conditioning, as well as transfer training, speech, swallowing, and cognitive evaluation.”

Id. at 47. She made “some progress” with the therapies by the time of her discharge to a subacute

rehabilitation center on September 30, 2016. Id.

On September 30, 2019, petitioner was transferred to The Evergreens, a subacute

rehabilitation facility for PT, OT, and speech therapy. Pet’r Ex. 6 at 59. By October 31, 2016, she

“regained use of [upper extremities] but continue[d] to require assistance for transfers [and]

toileting.” Id. at 13. By January 5, 2017, petitioner had made “excellent progress” with physical

therapy and could “function in her apartment.” Id. at 153. However, she would “need home PT to

continue progress toward maximal function.” Id. Petitioner was discharged home on January 6,

2017. Id.

8

iii. Continued Treatment at Home

Mr. Perez described petitioner’s home as a relatively small government-subsidized

apartment. Tr. 16. She used a wheelchair, walker, and rollator in the home, and would “walk the

hallways for her own physical therapy.” Id. She also had a shower seat installed in the home. Id.

at 17. Once petitioner was home, Mr. DiPonziano “had to do mostly everything for her,”

including putting her support stockings on, doing chores around the house, cooking, and

cleaning. Id. at 39-40. Petitioner could transition out of the wheelchair into a chair or her bed

with Mr. DiPonziano’s help. Id. at 40. She had about five or six falls in the apartment in the few

months after her discharge. Id. at 40, 45. On one occasion, she hit her head, but did not “have

any damage.” Id. at 41. She continued physical therapy treatment at home for approximately six

weeks. Id. at 41.

At a follow-up neurology appointment on February 3, 2017, petitioner had “continued

numbness in her fingertips” causing her to drop things. Pet’r Ex. 8 at 3. She also had “persistent

right foot drop, curled left toes, and numbness in both feet.” Id. She noted feeling unsteady with

her walker and that her arms were sore when “holding on tight to her walker.” Id. The motor

examination demonstrated strength levels of 4+/5 bilateral upper extremities, 3/5 right hip

flexion, 4-/5 left hip flexion, 4-/5 hip adduction and abduction, 4-/5 right knee extension, 4+/5

left knee extension, 2/5 right plantar flexion, 3/5 left plantar flexion, 2/5 right dorsiflexion, and

3+/5 left dorsiflexion. Id. at 7. Sensation was “intact throughout to all modalities” with

“diminished light touch on the right lower extremity.” Id.

Petitioner continued to see improvement throughout 2017 and into 2018. She received

physical therapy in her home twice per week until June 6, 2019. Pet’r Ex. 14 at 36. During this

time period, petitioner had several appointments with a new neurologist for an independent

opinion on her prognosis. Pet’r Ex. 10 at 1. At one of these appointments, on September 26,

2017, petitioner arrived in a wheelchair and showed “substantial improvement since her last

visit” four months earlier, as her left foot dorsiflexion strength was near normal. Id. at 4. At her

last appointment on January 9, 2018, she was able to transfer and walk short distances without an

assistive device. Id. at 6. She still had moderate right foot drop and mild left foot drop. Id.

Petitioner testified that she was not taking any medications related to GBS at the time of

the hearing, though she was previously taking “a lot of gabapentin,” approximately “600

milligrams…three time a day” which was eventually tapered. Id. at 67. She stopped physical

therapy in 2019 and had not seen her neurologist since that time. Id. at 65. At the time of the

hearing, petitioner was unable “to do the things she used to do prior to the GBS” but was able to

do all of the cooking, could do some cleaning, and would occasionally join Mr. DiPonziano and

a friend for shopping. Id. at 41. Petitioner had not received any treatment for GBS for the few

years prior to the hearing. Id. at 43.

9

III. Expert Opinions Regarding Vaccine Causation

a. Opinions of Petitioner’s Experts on Causation

i. Matthew C. Lee, MD, RPh, MS

Dr. Matthew Lee filed an expert report outlining his opinions in this case on July 26,

2019. Pet’r Ex. 11 (ECF No. 43). He was admitted and testified as an expert in pharmacology,

toxicology, and internal medicine at the entitlement hearing. Tr. 20. Dr. Lee opined that the

Prevnar-13 vaccine caused petitioner to develop GBS. Tr. 77-78. His overarching theory of

causation was that the vaccine caused GBS “through the immune response” and the inability of

the immune system to tell the difference between “the real bacteria” and “human host cells.” Tr.

79, 80-81.

Dr. Lee explained that GBS is characterized “by the acute or subacute onset of varying

degrees of weakness in limbs or cranial nerve-innervated muscles, [and] associated decreased or

absent deep tendon reflexes.” Pet’r Ex. 12 at 3. He further explained that “GBS is an immune-

mediated polyneuropathy…or [occurs] when there [is] a stimulus for the immune system that

evokes a response and the immune system actually attacks the nerves in the body.” Tr. 75. He

opined that petitioner’s course at Cooper University Hospital, including respiratory failure,

intubation, “and the further weakening of the nervous system,” was consistent with GBS and that

her case was “rather severe.” Id. at 87.

Dr. Lee explained that the Prevnar vaccine is a “13-valent conjugate vaccine containing

13 pneumococcal serotypes,” and exposure to the vaccine produces “an immune mediated

response, that makes organisms more vulnerable to host defenses.” Pet’r. Ex. 12 at 4. These “13

different strains of the strep pneumoniae bacteria …ha[ve] a coating on [them]” which is made

up of proteins that the immune system recognizes “as a foreign material.” Tr. 79. In other words,

“the little pieces of these protein coats are put into the vaccine without the infectious part of the

bacteria, and, that way, when the vaccine is administered, the body generates an immune

response. So if it encounters that bacteria as a real bacteria and not as a vaccine, it will generate

an immune response.” Id. The Prevnar vaccine specifically “has another protein added onto it

from the diphtheria [antigen] to evoke a larger immune response from the body.” Id. at 75. The

purpose of the protein is “to stimulate the immune system further and particularly [to stimulate]

the…T cell immune-mediated response.” Id. at 76.

Dr. Lee opined that the vaccine causes GBS “through the immune response” generated by

the vaccine. Id. at 79. He further explained that the immune response “is to look for road signs”

and that

ideally, the road signs are on the bacteria. However, in this case, the nerve cells in

the body also have similar road signs. So once the immune response is generated,

the body can’t tell the difference whether the road sign…is on the nerve or on the

bacteria. So that’s how the nerve cells are attacked by the body’s immune system

through that immune response created by the vaccine.

10

Tr. 79-80.

The body is unable to tell the difference between “the real bacteria” and “human host

nerve cells” because the proteins that the body “looks for, or the road signs…on the bacteria are

very similar to ones in the human body. So [the immune system] can’t tell the difference just

based on the road sign alone whether it’s something in the human or something on the bacteria.”

Id. at 80. He defined “road signs” as “the epitope proteins which are proteins on the surface of

bacteria, but also on the surface of human cells.” Id. at 80-81. More specifically, “the epitopes

are proteins on the surface of cells that the immune system is trained to recognize through

vaccination. [If] those epitopes are similar between a bacteria and nerve cells, then the immune

system will also attack the nerve cells that have similar epitopes as the bacteria.” Id. at 81.

To support this theory, Dr. Lee referenced articles by Haber and Sejvar. Id. at 82. The

Haber article is a vaccine reporting system post-licensure surveillance review which specifically

discusses the Prevnar 13 vaccine and found that “in persons over the age of 65 that received

Prevnar 13, there were 10 to 11 cases reported [to VAERS] for GBS.” Id.; Pet’r Ex. 9.2 at 5. 10

According to Dr. Lee, the Sejvar article “describes the cross-reaction with the epitopes on

peripheral nerve roots.” Tr. 82; Pet’r Ex. 11.1. 11 The study notes that “vaccines are another

antigenic stimulus for which potential associations with GBS have been reported” and that “with

rare exceptions, the biological or epidemiological evidence for a causal association between GBS

and antecedent infections or vaccination is equivocal.” Pet’r Ex. 11.1 at 1-2.

Dr. Lee opined that there was a clear proximate temporal relationship of cause and effect

between the vaccination and petitioner’s injury given the timeline of vaccine administration and

the onset of petitioner’s symptoms. Tr. 84. In petitioner’s case, it took her body 11 days “to

generate the immune response and for the antibodies to attack the epitopes on her nerve cells.”

Id. He relied on the Haber article to support his opinion that 11 days falls within the accepted

timeline for causation. Id. at 84-85. That article found that, in eleven “reports of possible GBS

after PCV13 the median onset interval of symptoms was [nine] days,” with a range of two to 34

days. Pet’r Ex. 9.2 at 4.

Finally, Dr. Lee addressed the theory of respondent’s experts that petitioner had an upper

respiratory infection (“URI”), which caused her to develop GBS as opposed to the vaccine. Tr.

85-86. He first disagreed that petitioner was diagnosed with a URI, noting that “she reported

upper respiratory symptoms upon presentation to the ER but she had not undergone treatment or

evaluation by a medical doctor to have that diagnosis.” Tr. 86. Typical symptoms for a

respiratory infection include “chest tightness, shortness of breath, wheezing, [and] sputum

10

Penina Haber, et al., Post-licensure surveillance of 13-valent pneumococcal conjugate vaccine (PCV13) in adults

aged > 19 years old in the United States, Vaccine Adverse Event Reporting System (VAERS), June 1, 2012 – Dec.

31, 2015, 34 Vaccine 6330 (2016).

11

James H. Sejvar, et al., Population Incidence of Guillain-Barre Syndrome: A Systematic Review and Meta-

Analysis, 36 Neuroepidemiology 123 (2011).

11

production.” Id. at 87. A URI is typically diagnosed based on history, onset, and

symptomatology including presence of fever, cough, whether the cough is productive or

nonproductive, runny nose, and chest tightness. Id. at 96. Other factors considered when

diagnosing a URI include “the time of year…where [the patient] has been, if they have a history

of allergies, if they’ve traveled, if they have other comorbid conditions, such as COPD…or

diabetes or heart disease.” Id. Referring to an examination by the ED provider at Cooper

University Hospital, Dr. Lee opined that the review of systems and physical examination support

the fact that petitioner “did not have an upper respiratory tract infection.” Id. at 102-03; Pet’r Ex.

3.1 at 57. Dr. Lee also opined that, “if there was a URI present, [it] was not present long enough

to generate the immune response that would be necessary to cause GBS.” Tr. at 353. The

medical record indicated URI symptoms for four days at the time of admission. Id. at 334. Dr.

Lee noted that she was not treated for an upper respiratory infection at the hospital and that it

appeared that the symptoms were not present at that time. Id. at 353. He testified that if

untreated, a URI typically takes three to seven days to resolve, but “the exaggerated immune

response that is responsible for GBS would take longer to develop than just the immune response

against the pathogen causing the URI.” Id. at 354-55.

ii. Robert L. Knobler, MD, PhD

Petitioner submitted an expert report from Dr. Knobler on July 26, 2019. Pet’r Ex. 11. Dr.

Knobler was admitted and testified “as an expert in the field of neurology with special

qualifications in neuroimmunology” at the entitlement hearing. Tr. 120. Dr. Knobler opined that

petitioner “developed GBS following immunization with Prevnar 13.” Pet’r Ex. 11 at 5; Tr. 122.

He proposed two possible causal theories at the hearing as to how a vaccine can cause GBS,

molecular mimicry and “collateral damage.” Tr. 146-47. At the first hearing, Dr. Knobler opined

that “that collateral damage” theory was more likely “the responsible mechanism” as opposed to

molecular mimicry. Id. at 148. However, at the continuation of the hearing about a month later,

he testified that the cause of petitioner’s GBS more likely than not was due “to an element of

molecular mimicry.” Id. at 219.

Dr. Knobler testified that GBS “is a disorder that most frequently occurs following some

type of immune perturbation disturbance that can be caused by a variety of different causes.” Tr.

121. He further explained that “there is typically a time course that is involved between the

precipitating event and the onset of clinical symptoms” which “involves the presentation of

various neurological symptoms relating to the loss of the insulation of nerve fibers in the

peripheral nervous system…” Id. In other words, GBS involves “a precipitating event, a timeline

to which that leads to the loss of myelin, the insulation surrounding nerve fibers, and that there

may be damage to the nerve fibers…and subsequently neurologic symptoms as a consequence of

that pathological change.” Id. at 121-22.

Dr. Knobler noted that “many of the components of the process by which” GBS develops

“in any individual are highly variable” and “depends on circumstance.” Tr. 197. To determine

such mechanism, one must “search for what factors…have been associated with [GBS].” Id. at

197-98. He further explained that “factors such as infections and vaccinations are two of the

most common causative agents that are associated with” GBS. Id. at 198. Temporal association

12

“meaning the timeline in which those events occur, have proven pivotal in terms of that

association.” Id. Moreover, Dr. Knobler cited to the same analysis by Haber as Dr. Lee to show

that “there is an association between GBS and having received [the] Prevnar vaccine.” Id. at 146.

Dr. Knobler explained that, with his collateral damage theory, “any vaccine has the

potential in an individual of stimulating the immune system…and if it stimulates the immune

system in a particularly susceptible individual…that stimulation of the immune system can lead

to development of Guillain-Barre.” Tr. 123-24. Importantly, “the immune system response can

be misdirected in certain individuals and can lead to loss of tissue. One of the ways in which that

happens is the development of GBS…” Id. at 125. Such misdirection can occur “in a variety of

ways,” one of which “is an immediate early type of response.” Id. In this scenario, “when an

antibody binds to a target, the Fc portion is left protruding, and a cell called a

macrophage…attaches to the Fc portion of the antibody molecule and then it produces damage to

the tissue.” Id. at 125-26. In other words, “if there is binding of an antibody to a target, the Fc

portion is then left to attract the macrophage, which is recruited to the area, and that activated

macrophage will produce damage to the tissue that the antibody is attached to.” Id. at 126. More

specific to GBS, “if the antibody attaches to myelin, [the macrophage] will produce damage to

myelin.” Id. He noted that “when we look at GBS as an example, we look at how an antibody

binds to a tissue and the time course that it takes for that antibody to be produced and the time it

takes for the macrophages to produce damage.” Id. at 126-27. Such damage can occur “anywhere

from four days, at the absolute shortest if the system is primed, to usually somewhere closer to

between seven and 14 days.” Id. at 127.

Dr. Knobler explained that the Prevnar vaccine has elements of multiple “different strains

of the pneumococcus bacteria and components of them that stimulate the immune system in

order to provide a level of protection against infection…” Id. at 123. He explained the

connection between the Prevnar vaccine and GBS response is “based on [the] general [immune

system] response,” noting that “there [are] a number of different [causal] mechanisms that have

been investigated over the years.” Id. at 127. He specifically referenced two such mechanisms,

molecular mimicry and “nonspecific stimulation of the immune system.” Id. at 127-28.

Dr. Knobler later characterized the “nonspecific stimulation of the immune system” as a

“collateral damage hypothesis,” which he defined as “immune sensitization and development of

an immune response.” Id. at 147, 159. When asked about the generality of the term “collateral

damage,” Dr. Knobler agreed that it could refer to “both the response of the innate and the

adaptive immune system…when damage occurs.” Id. at 159-60. He explained that collateral

damage occurs when “the immune system responds by ingesting a target antigen, processing that

target antigen, and then responding to it.” Id. at 200. While the immune system is “meant to

protect us…sometimes its impact is such that it can produce overwhelming damage.” Id.

He referred to an article by Yuki and Hartung, 12 published in the New England Journal of

Medicine, to support his theory that, under the collateral damage hypothesis, an “antibody binds

to a target and then the activated macrophages swoop in” which “leads to damage of the tissue.”

Tr. 159-61. This study found “evidence of early complement activation, which is based on an

antibody binding to the outer surface of the Schwann cell and deposition of activated

12

Nobuhiro Yuki & Hans-Peter Hartung, Guillain-Barre Syndrome, 366 New England J. of Medicine 304 (2012).

13

complement components; such complement activation appears to initiate the vesiculation of

myelin. Macrophage invasion is observed within one week after complement-mediated myelin

damage occurs.” Pet’r Ex. 12.5 at 4. This explanation by Yuki, Dr. Knobler testified, describes

the general immune system response described in his testimony. Tr. 160-61.

Dr. Knobler explained that identification of a specific antigen is not needed to show how

the Prevnar vaccine can cause GBS under his collateral damage theory, as only “stimulation of

the immune system” is required. Tr. 147. In some instances, an adjuvant, such as the one used in

the Prevnar vaccine, may be used to “stimulate a more vigorous immune response,” which “is

one of the ways in which collateral damage can occur.” Id. at 147-48.

On questioning by the Court, Dr. Knobler stated that his theory in this case was

consistent with the discussion in the case report by Ravishankar, which specifically discusses

pneumococcal vaccines. 13 Tr. 177-78; Pet’r Ex. 12.3 at 1. The article explained that:

there are two types of pneumococcal vaccines, plain and conjugated, that have

different mechanisms…Conjugated vaccines elicit a T-cell dependent response.

The polysaccharide conjugated to a carrier protein used MHC class-II dependent

response to present the carrier protein to carrier-peptide-specific helper T cells.

This leads to enhancement of the B-cell immune response, so that the antibody

response is of greater specificity and functionality.

Pet’r Ex. 12.3 at 2.

Citing to the Ravishankar article Dr. Knobler agreed with the author’s conclusion that “it

can be inferred that the conjugated [Prevnar] vaccine produces the enhanced B-cell immune

response leading to autoimmune reaction to the peripheral nerves,” which is consistent with his

theory in this case. Id.

When specifically asked whether his collateral damage theory could be characterized as

bystander activation, as respondent’s expert, Dr. He suggested, Dr. Knobler explained that the

antibody form of immune response is a humoral response or there could be a T cell response

involving T cells and macrophages. In a bystander activation, the immune system is stimulated to

provide a broad spectrum of responses, and, as a result, there can be an overwhelming activation

of the immune system. Thus, he said, bystander reactions do occur. Collateral damage also

occurs, but that does not negate the fact that specific pathogens can precipitate them. Tr. 201.

When asked to explain further in response to Dr. He’s report, Dr. Knobler testified that a

bystander activation is an example of the immune system’s exuberance in a particular individual.

The immune response is complex and it will respond to what it sees and to what it is genetically

programmed to be able to do. There is variability from individual to individual. Some people are

very high responders some are low responders. So, he testified, that when you administer an

agent such as a vaccine, you are taking a risk that a person will have a broad response that is not

expected, which is the bystander effect. Tr. 203-206.

13

Nidhi Ravishankar, Guillain-Barre Syndrome Following PCV Vaccine, 4 J. Neurology & Neurosurgery 134

(2017).

14

Dr. Knobler then addressed his molecular mimicry theory. He explained that while “the

precise mechanism by which [GBS] is caused has not yet been fully clarified…one of the

mechanisms proposed in some forms of GBS has been that of molecular mimicry, in which

either the precise sequence or overall structure of a host cell and infectious agent coincide.” Id. at

4. He testified that “the immune response directed against that target is similar…to a naturally

occurring substance.” Tr. 127. Further he explained that,

molecular mimicry is a well-established mechanism in the laboratory and in

nature. It has been documented in humans to exist where either the specific

sequence of a substance or shape of a substance provides stimulation to the

immune system, and that allows recognition of a target on an individual, and

vulnerable targets, such as the myelin sheath in a disease like GBS, can be

affected by that.

Id. at 128. Dr. Knobler further testified that “there can be components in a vaccine, as an

example, in which…either the sequence or structure resembles a sequence or structure within the

body. And so the immune response that is being stimulated by that vaccine is then going to target

a comparable sequence or structure in the individual.” Id. at 213. He said that is what molecular

mimicry is in real life. Id. He further explained on rebuttal that his proposed molecular mimicry

mechanism could be described an immune response directed against target antigens of potential

agents that may cross-react with molecules in the nervous system. Id. at 358.

As to whether the Prevnar vaccine caused petitioner’s GBS, after explaining the theory of

molecular mimicry, Dr. Knobler opined that, more likely than not, the vaccination was the

precipitating event resulting in petitioner’s development of GBS. Tr. 130, 219. His opinion was

based on the time course in which petitioner was vaccinated and the development of symptoms

within 10 days of the vaccination, leading to a GBS diagnosis and hospitalization. Id. at 217. He

explained that this “is within the expected time course for such an event to occur, and there were

no other documented events that occurred that would provide an alternative explanation for this.”

Id. at 130. Although at the initial hearing, he favored a more general theory of immune causation

triggered by the vaccine which he called the collateral damage theory, at the continuation of the

hearing on October 21, 2021, Dr. Knobler opined that, based on his clinical experience,

laboratory experience, and his understanding of the medical literature, “the more likely than not

explanation is that an element of molecular mimicry played a role in causation with respect to the

vaccine.” Id. at 219-20. He testified that he believed that molecular mimicry between the vaccine

and the myelin was the most likely mechanism and that more likely than not it was molecular

mimicry that was associated with the petitioner’s GBS. Id.

Dr. Knobler also addressed the theory of respondent’s experts that petitioner had an upper

respiratory infection, which caused her to develop GBS, opining that, based on petitioner’s

examination in the Cooper University Hospital ED, “there was no indication…that [petitioner]

had an upper respiratory infection” or any infectious process. Tr. 181-83; Pet’r Ex. 3.1 at 57.

More specifically, he opined that the examination of petitioner’s mouth and throat, where an

upper respiratory infection would be located, showed no signs of infection. Tr. 183. Although the

term “URI” was listed in petitioner’s medical records, “there were no features of URI that were

observed in the emergency department. There was no history of URI that occurred.” Id. at 130.

15

Dr. Knobler agreed that “there were generic symptoms reported that could have been due

to…anything,” but “there was no fever; there was no sneezing; there was no runny nose, not

even the simplest form of a URI.” Id. Instead of a URI, Dr. Knobler opined that petitioner was

most likely suffering from allergic rhinitis. Id. at 130. He explained that, given the time of year,

“the likelihood of a cold or a flu or upper respiratory infection [is] far less likely simply because

the infectious agents are not typically active in July.” Id. at 131. He observed that petitioner had

a history of allergies. He also noted that the timeline in petitioner’s case “fits more appropriately

and more closely, more directly with” the vaccination as opposed to a URI. Id. at 198, 217, 359.

He testified that the timeline of 10 to 11 days strongly favored the vaccine as the causative agent

as it generally takes seven to 10 days to mount the immune response. So even if she had a URI

which he did not think likely the URI symptoms were not present long enough to generate the

immune response that would be necessary to cause GBS. Id. at 353.

iii. Dr. Robert C. Hyzy, M.D.

Dr. Robert Hyzy, an internal medicine physician, did not testify at the hearing but

submitted an expert report outlining his opinions. Pet’r Ex. 9. Dr. Hyzy opined that “the

vaccination of [petitioner] was the cause of her GBS” and that there is “a logical sequence of

cause and effect as the vaccination with Prevnar-13 was the reason for the injury and exhibited

an appropriate temporal relationship between the vaccination and her injury.” Id. at 2

Dr. Hyzy supported his conclusion with the Haber post-licensure surveillance study and

noted that the article and the facts therein “clearly establish a causal relationship between the

vaccination with Prevnar-13 and the onset of GBS.” Id. He also noted that the article found a

mean onset of symptoms of 9 days, with petitioner developing GBS eleven days after

vaccination, “clearly within the expected range of onset of GBS following Prevnar-13.” Id.

b. Opinions of Respondent’s Experts on Causation

i. You Wen He, MD, PhD

Respondent filed two expert reports from Dr. You-Wen He, who was admitted and

testified as an expert in immunology. Resp’t Ex. D; Resp’t Ex. G; Tr. 230. Dr. He did not dispute

that GBS was the proper diagnosis in this case. Tr. 232. However, he opined that there was no

“evidence, no mechanism that can link PCV 13 to GBS.” Id. at 231.

Dr. He characterized GBS as “an inflammatory polyneuropathy characterized by an acute

onset, rapid progression, symmetric muscle weakness, and hyporeflexia or areflexia.” Resp’t Ex.

D at 2. He noted that the “incidence of GBS is 0.5-2 per 100,000 per year and it occurs during all

seasons.” Id. He agreed that GBS is an immune-mediated condition, which can be defined

broadly as “immune cell participation.” Tr. 232. Dr. He opined that infections are one of the

most common causes of GBS and noted that “two-thirds of GBS” cases were seen in “patients

with prior infection history, either URI or [gastrointestinal] tract.” Id. However, he agreed that

“vaccines are known …to cause GBS,” and further explained that “the exact mechanism for [a]

certain vaccine to cause GBS is unknown.” Id. at 278. Whether a vaccine “has an effect on

GBS…really boils down to what specifically the vaccine is.” Id. at 249. When looking at the

16

Prevnar 13 vaccine, Dr. He found only weak evidence for an effect on GBS. Id. Dr. He also went

through some of the medical literature filed by petitioner and testified that he does not believe

any of the literature supports a link between the Prevnar vaccine and GBS, other than a temporal

relationship. See id. at 260-71, 302-04. He agreed that, in the present case, petitioner had a

temporal relationship between her vaccination and GBS. Id. at 308.

Dr. He primarily disputed Dr. Knobler and Dr. Lee’s causation theories based on the

strength of the vaccine and the type of immune response it generates. He agrees that vaccines can

cause GBS, noting the 1976 swine flu vaccine as an example. However, he testified that when he

looked at the PCV 13 vaccine he concluded that it is a relatively weak vaccine compared to

others. He explained that the vaccine contains what he called very simple components or

pathogen associated molecular patterns (“PAMPS”). The vaccine contains a polysaccharide

conjugated to a carrier protein from diphtheria serum 1. He argued that using just the

polysaccharide as an immune stimulant will not induce an antibody response that will last. He

testified that the diphtheria component is necessary to stimulate a CD4 T helper response that is

necessary for a lasting antibody response. Tr. 249. He acknowledged that the vaccine contains an

adjuvant that is added to the vaccine to stimulate a more aggressive immune response and may

also play a role in macrophage activation among other things. Id. at 250.

Dr. He discussed the difference in the “extent of the invasion” between a wild pathogen

and a vaccine using the pneumococcus bacteria and Prevnar vaccine as an example. Tr. 238-41.

The pneumococcus bacteria has “many different…pathogen-associated molecular patterns”

which, in turn “will be sensed by so many different…receptors at the same time” giving a broad

activation of the immune system. Id. at 238. The Prevnar vaccine, on the other hand, “only

contains one type of molecular pattern” called polysaccharides, which “will engage one type of

receptor, C-type lectin on [the] subsurface, [and] will not engage, for example, toll-like receptor

9.” Id. at 238-39. Thus, when someone receives the pneumococcal vaccine, “they will have [the]

antibody against the polysaccharide” whereas a patient who has the wild infection will have the

antibody against the polysaccharide and other components of the bacteria. Id. at 240-41. He also

derided Dr. Knobler’s explanation of the immune system as being overly basic and out of date.

Id. at 235. He was critical of the failure to discuss PAMPS and DAMPS and the roll of Toll Like

Receptors. Id. at 236-37. He took particular issue with Dr. Knobler’s testimony that tolerance

was not important to the discussion in this case. See, e.g., id. at 243. Dr. He explained this

theory, noting that “for every type of positive force, there’s a negative counterforce.” Id. at 245.

Part of the negative counterforce is “immune check point receptors,” which “keep our immune

system under control.” Id. at 245. The Prevnar vaccine, for example, will “activate the dendritic

cells and the macrophages, and those cells, once they’re activated, [will] automatically start to

express this counterforce called PD-1, PDL-1, and ligand adjuvant.” Id. at 246.

Dr. He disagreed with Dr. Lee and Dr. Knobler’s opinions that the immune response to a

wild virus and the immune response to a vaccine are the same. Tr. 235-36. Consistent with his

emphasis on the volume of the immune response he said infections are an uncontrolled process

with unknown aim and components, whereas vaccines are controlled. Id. at 236. He explained

that “pattern recognition receptors…have the ability to sense different patterns from the

pathogen,” and that petitioner’s expert did not include this in his theory. Id. at 237-38. He further

explained how pattern recognition receptors work with the following example:

17

For example, Toll-like receptor 4 will see only one type of component from the

pathogen called LPS, and Toll-like receptor 2 will sense…another one, called

peptide ligand from Gram-positive bacteria and LPS is mostly from Gram-

negative bacteria. And the virus will have [a] specific pattern for receptor 2…So

for each component, we’ll have a different type of pattern recognition receptors to

sense it.

Id. at 237.

In response to Dr. Knobler’s “collateral damage” theory of causation, Dr. He noted that

“there is no such term called ‘collateral damage’ to refer to [an] autoimmune disease

mechanism.” Tr. 233. Rather, Dr. He characterized Dr. Knobler’s theory as “a nonspecific

activation of the immune system” resulting in damage caused by “nonspecific activated cells like

macrophage[s].” Id. He testified that this nonspecific activation is termed “bystander activation,”

which “happens all the time.” Id. He testified that bystander activation occurs every time “there

is a foreign subject invading our body.” Id. at 234. While bystander activation is “a common

phenomenon,” it is not common for it to cause damage leading to GBS. Id. at 234-35. He

acknowledged that bystander activation can at times cause damage leading to an autoimmune

disease. Id. at 233. Specific to vaccines, Dr. He explained that “when we receive a vaccine, we

will have this bystander activation but” whether this bystander activation causes damage depends

on the extent of the activation. Id. at 245. If the activation “is too much, [it] will cause damage. If

it’s not too much, our counterbalance, the central tolerance mechanism will come into play.” Id.

Dr. He also agreed that lectins in the body can bind to the polysaccharides in a vaccine and can

stimulate an immune response which, when uncontrolled, can cause “collateral damage.” Id. at

282-83. Whether or not lectin cells cause damage after activation by a carbohydrate requires a

break of the “tolerance mechanism.” Id. at 284. Dr. He argued that stimulation of the immune

system by activated lectin cells would not cause GBS because of “immune control.” Id. at 283.

Importantly, however, he agreed that “in any case of GBS, the immune control system doesn’t

work,” and further explained that “if the control works properly…you will not get GBS.” Id.

In addressing petitioner’s molecular mimicry theory, Dr. He agreed that “cross-reactive

autoantibodies may play some role in…GBS development.” Tr. 286. However, he argued that

“cross-reactive antibod[ies] and cross-reactive T cell epitopes exist in our body all the time.” Id.

at 243, 286. This cross-reactivity is only “part of the molecular mimicry theory,” though it is “the

most important thing,” as “cross-reactivity is needed to break [the] tolerance mechanism [and]

cause damage.” Id. at 287-88. However, these cross reactions are controlled through tolerance.

Id. at 243-45. Dr. He agreed that “if there’s a component in the [Prevnar] vaccine that cross-

reacts with something in the Schwann cells or in the myelin, whether it’s a strong vaccine or a

weak vaccine, autoimmunity could occur in someone who’s genetically susceptible and tolerance

breaks down.” Id. at 259. However, Dr. He explained that there is “no evidence…[that] PCV 13,

the polysaccharide, has anything to do with any of the proteins involved in GBS.” Id.

Dr. He highlighted petitioner’s preceding URI symptoms as a possible alternative cause

for her GBS, noting that “two thirds of [GBS] cases” relate to URIs or GI tract infections. Tr.

18

272. According to the article by Willison et al., 14 submitted by Dr. He, URI or gastrointestinal

symptoms were reported within four weeks prior to onset of GBS in two thirds of patients.

Resp’t Ex. D-2 at 2. However, the same article recognized that other immune stimulation

including by vaccines also causes aberrant autoimmune responses targeting peripheral nerves

and their spinal roots. Id. at 1. He noted that the initial neurology consultation petitioner had at

Cooper University Hospital noted that the GBS was “likely precipitated by [a] recent URI,” and

later agreed that the records also included the vaccine as a potential cause. Id. at 272, 301-02. Dr.

He opined that petitioner had a URI at the time of her ED visit based on her symptoms, including

“cough congestion…[and] runny nose.” Id. at 279. He explained that these are “classic URI

symptoms” but agreed that they could also be “symptoms of an allergic response to…a pollen

allergy.” Id. Regardless of whether petitioner had a URI, Dr. He did not believe that the Prevnar

vaccine caused petitioner’s GBS. Id. at 297-98. Dr. He agreed that, by ten- or eleven-days post

vaccination, the vaccine would have generated an immune response and that by three to five

days, if petitioner had a URI, the immune system would have generated a response to that as

well. He agreed that it was possible that the combination of the two acting at the same time could

have caused a sufficiently overwhelming response to cause autoimmunity. Tr. 312-13.

ii. Brian Callaghan, MD

Respondent filed three expert reports from Dr. Brian Callaghan, who was admitted and

testified as an expert in neurology and electrodiagnostic medicine. Resp’t Ex. A; Resp’t Ex. C;

Resp’t Ex. F; Tr. 319. Dr. Callaghan’s theory is that petitioner’s “medically documented” URI

constitutes a clear “nonvaccine cause” of her GBS and that there “is no evidence to support” a

causal link between Prevnar and GBS. Tr. 321. While Dr. Callaghan generally agreed with Dr.

He that there was no known evidence that Prevnar could cause GBS, the bulk of his testimony

addressed the possible upper respiratory infection as a cause and will be addressed under the

analysis of alternative cause below.

Dr. Callaghan disputed that petitioner’s experts presented “a reliable or reputable theory

for how the Prevnar 13 vaccine could cause petitioner’s GBS” noting that “the theory has been

very hard to get a cogent understanding of.” Tr. 323. He understood Dr. Lee’s theory as

molecular mimicry and Dr. Knobler’s theory to be molecular mimicry and “a nonspecific

immune stimulation argument.” Id. He did not think that either theory supports a causal

connection between the Prevnar vaccine and GBS. Id. He noted that “molecular mimicry

requires several steps of proof to determine that that’s a causal mechanism” and that the

nonspecific immune stimulation theory “could mean that any precipitant could cause any

disease.” Id. at 324.

Dr. Callaghan addressed the medical literature filed by petitioner’s experts. He noted that

the Yuki article discusses the 1976 swine flu vaccine and had “epidemiological literature to

associate that vaccine with GBS,” and he agreed that the swine flu vaccine was associated with

GBS. Tr. 328. The rest of the article, he observed, discussed GBS generally and is not vaccine

specific. Id. He noted that the pathogenesis of GBS discussed in the Yuki article and relied on by

Dr. Knobler shows “what we don’t know about GBS pathogenesis, because basically they’re

14

Willison et al., Guillain Barre Syndrome, 388 Lancet 717, 718 (2016).

19

invoking pretty much every piece of the immune system, whether it be…complement antibodies

or T cells” and is more of a general description. Id. at 329.

IV. Legal Standard

The Vaccine Act was established to compensate vaccine-related injuries and deaths. §

10(a). “Congress designed the Vaccine Program to supplement the state law civil tort system as a

simple, fair and expeditious means for compensating vaccine-related injured persons. The

Program was established to award ‘vaccine persons quickly, easily, and with certainty and

generosity.’” Rooks v. Sec’y of Health & Hum. Servs., 35 Fed. Cl. 1, 7 (1996) (quoting H.R. Rep.

No. 908 at 3, reprinted in 1986 U.S.C.C.A.N. at 6287, 6344).

Petitioner’s burden of proof is by a preponderance of the evidence. § 13(a)(1). The

preponderance standard requires a petitioner to demonstrate that it is more likely than not that the

vaccine at issue caused the injury. Moberly v. Sec’y of Health & Hum. Servs., 592 F.3d 1315,

1322 n.2 (Fed. Cir. 2010). Proof of medical certainty is not required. Bunting v. Sec’y of Health

& Hum. Servs., 931 F.2d 867, 873 (Fed. Cir. 1991). In particular, petitioner must prove that the

vaccine was “not only [the] but-for cause of the injury but also a substantial factor in bringing

about the injury.” Moberly, 592 F.3d at 1321 (quoting Shyface v. Sec’y of Health & Hum. Servs.,

165 F.3d 1344, 1352-53 (Fed. Cir. 1999)); see also Pafford v. Sec’y of Health & Hum. Servs.,

451 F.3d 1352, 1355 (Fed. Cir. 2006). A petitioner who satisfies this burden is entitled to

compensation unless respondent can prove, by a preponderance of the evidence, that the

vaccinee’s injury is due to factors unrelated to the administration of the vaccine.” § 13(a)(1)(B).

To receive compensation through the Program, petitioner must prove either (1) that she

suffered a “Table Injury”— i.e., an injury listed on the Vaccine Injury Table — corresponding to

a vaccine that she received, or (2) that he suffered an injury that was actually caused by a

vaccination. See §§ 11(c)(1), 13(a)(1)(A); Capizzano v. Sec’y of Health & Hum. Servs., 440 F.3d

1317, 1319-20 (Fed. Cir. 2006). Because petitioner does not allege that she suffered a Table

Injury, she must prove that a vaccine she received caused her injury. To do so, she must

establish, by preponderant evidence: (1) a medical theory causally connecting the vaccine and

her injury (“Althen Prong One”); (2) a logical sequence of cause and effect showing that the

vaccine was the reason for her injury (“Althen Prong Two”); and (3) a showing of a proximate

temporal relationship between the vaccine and her injury (“Althen Prong Three”). § 13(a)(1);

Althen v. Sec’y of Health & Hum. Servs., 418 F.3d 1274, 1278 (Fed. Cir. 2005). The causation

theory must relate to the injury alleged. The petitioner must provide a sound and reliable medical

or scientific explanation that pertains specifically to this case, although the explanation need only

be “legally probable, not medically or scientifically certain.” Knudsen v. Sec’y of Health & Hum.

Servs., 35 F.3d 543, 548-49 (Fed. Cir. 1994). The Federal Circuit has reiterated that proof of

causation does not “require identification and proof of specific biological mechanisms[.]”

Kottenstette v. Sec’y of Health & Hum. Servs., 861 F. App’x 433, 441 (Fed. Cir. 2021) (citing

Knudsen, 35 F.3d at 549). Causation “can be found in vaccine cases…without detailed medical

and scientific exposition of the biological mechanisms.” Knudsen, 35 F.3d 543 at 548-49. It is

not necessary for a petitioner to point to conclusive evidence in the medical literature linking a

vaccine to the petitioner’s injury, as long as the petitioner can show by a preponderance of

20

evidence that there is a causal relationship between the vaccine and the injury, whatever the

details of the mechanism may be. Moberly, 592 F.3d at 1325.

Petitioner cannot establish entitlement to compensation based solely on his assertions;

rather, a vaccine claim must be supported either by medical records or by the opinion of a

medical doctor. § 13(a)(1). In determining whether petitioner is entitled to compensation, the

special master shall consider all material in the record, including “any…conclusion, [or] medical

judgment…which is contained in the record regarding…causation.” § 13(b)(1)(A). The

undersigned must weigh the submitted evidence and the testimony of the parties’ proffered

experts and rule in petitioner’s favor when the evidence weighs in his favor. See Moberly, 592

F.3d at 1325-26 (“Finders of fact are entitled—indeed, expected—to make determinations as to

the reliability of the evidence presented to them and, if appropriate, as to the credibility of the

persons presenting that evidence.”); Althen, 418 F.3d at 1280 (noting that “close calls” are

resolved in petitioner’s favor).

In Vaccine Act cases, expert testimony may be evaluated according to the factors for

analyzing scientific reliability set forth in Daubert v. Merrell Dow Pharm., Inc., 509 U.S. 579,

594-96 (1993); see also Cedillo v. Sec’y of Health & Hum. Servs., 617 F.3d 1325, 1339 (Fed.

Cir. 2010) (citing Terran v. Sec’y of Health & Hum. Servs., 195 F.3d 1302, 1316 (Fed. Cir.

1999)). In Vaccine Program cases, the Daubert analysis has been used in weighing scientific

evidence actually proffered and heard rather than as a tool for the pre-trial exclusion of expert

testimony. Davis v. Sec'y of Health & Hum. Servs., 94 Fed. Cl. 53, 66–67 (2010) (“uniquely in

this Circuit, the Daubert factors have been employed also as an acceptable evidentiary-gauging

tool with respect to persuasiveness of expert testimony already admitted”), aff'd, 420 F. App'x

923 (Fed. Cir. 2011). The flexible use of the Daubert factors to determine the persuasiveness

and/or reliability of expert testimony in Vaccine Program cases has routinely been upheld. See,

e.g., Snyder v. Sec'y of Health & Hum. Servs., 88 Fed. Cl. 706, 742–45 (2009).

Where both sides offer expert testimony, a special master's decision may be “based on the

credibility of the experts and the relative persuasiveness of their competing theories.”

Broekelschen v. Sec'y of Health & Hum. Servs., 618 F.3d 1339, 1347 (Fed. Cir. 2010) (citing

Lampe v. Sec’y of Health & Hum. Servs., 219 F.3d 1357, 1362 (Fed. Cir. 2000)). However,

nothing requires the acceptance of an expert's conclusion “connected to existing data only by the

ipse dixit of the expert,” especially if “there is simply too great an analytical gap between the

data and the opinion proffered.” Snyder, 88 Fed. Cl. at 743 (quoting Gen. Elec. Co. v. Joiner, 522

U.S. 146 (1997)). Weighing the relative persuasiveness of competing expert testimony, based on

a particular expert's credibility, is part of the overall reliability analysis to which special masters

must subject expert testimony in Vaccine Program cases. Moberly, 592 F.3d at 1325–26

(“[a]ssessments as to the reliability of expert testimony often turn on credibility

determinations”); see also Porter v. Sec'y of Health & Hum. Servs., 663 F.3d 1242, 1250 (Fed.

Cir. 2011) (“this court has unambiguously explained that special masters are expected to

consider the credibility of expert witnesses in evaluating petitions for compensation under the

Vaccine Act”).

Close calls regarding causation must be resolved in favor of the petitioner. Althen, 418

F.3d at 1280 (holding that Congress created a system in which “close calls regarding causation

21

are resolved in favor of injured claimants”); Knudsen, 35 F.3d at 551 (“If the evidence (on

alternative cause) is seen in equipoise, then the government has failed in its burden of persuasion

and compensation must be awarded.”).

V. Analysis

Petitioner’s diagnosis of GBS was not contested by the respondent. Petitioner received

the Prevnar 13 vaccine on July 11, 2016 and began experiencing the symptoms of GBS on July

22, 2016. All experts agreed that petitioner was correctly diagnosed with GBS and that GBS is

generally considered to be an autoimmune disease. Thus, the only issue for determination is

whether petitioner has established by a preponderance of the evidence that the Prevnar 13

vaccine she received on July 11, 2016 was a substantial factor in causing her subsequent GBS.

Shyface, 165 F.3d at 1352.

a. Althen Prong One

Under Althen prong one, petitioner must provide a “reputable medical theory,”

demonstrating that the vaccine received can cause the type of injury alleged. Pafford, 451 F.3d at

1355-56. Such theory must only be “legally probable, not medically or scientifically certain.”

Knudsen, 35 F.3d 548-49. Petitioner may satisfy the first Althen prong without resort to medical

literature, epidemiological studies, demonstration of a specific mechanism, or a generally

accepted medical theory. See Andreu v. Sec’y of Health & Hum. Servs., 569 F.3d 1367, 1378-79

(Fed. Cir. 2009) (citing Capizzano, 440 F.3d at 1325-26). However, a “petitioner must provide a

‘reputable medical or scientific explanation’ for [her] theory.” Boatmon v. Sec’y of Health and

Hum. Servs., 941 F.3d 1351, 1359 (Fed. Cir. 2019) (quoting Moberly, 592 F.3d at 1322). While

the theory need not be medically or scientifically certain, “it must still be ‘sound and reliable’”

Id. (quoting Knudsen, 35 F.3d at 548-49). The petitioner must provide a sound and reliable

medical or scientific explanation that pertains specifically to this case, although the explanation

need only be “legally probable, not medically or scientifically certain.” Knudsen, 35 F.3d at 548-

49. In Kottenstette, the Federal Circuit reiterated that proof of causation does not “require

identification and proof of specific biological mechanisms[.]” 861 F. App’x at 441 (citing

Knudsen, 35 F.3d at 549). Causation “can be found in vaccine cases…without detailed medical

and scientific exposition of the biological mechanisms.” Knudsen, 35 F.3d at 548-49.

In their article entitled Guillain-Barre syndrome 15 filed by respondent, Hugh Willison and

colleagues discussed the pathogenesis of GBS:

First, Guillain-Barre syndrome is usually preceded by infection or other immune

stimulation that induces an aberrant autoimmune response targeting peripheral

nerves and their spinal roots. Molecular mimicry between microbial and nerve

antigens is clearly a major driving force behind the development of the disorder,

at least in the case of Campylobacter jejuni. However, the interplay between

microbial and host factors that dictates if and how the immune response is shifted

towards unwanted autoreactivity is still not well understood. Furthermore, genetic

15

Willison et al, Guillain-Barre syndrome, 388 The Lancet 717 (2016).

22

and environmental factors that affect an individual ‘s susceptibility to develop the

disease are unknown.

Resp’t Ex. D-2 at 1.

Willison further noted that greater than 99% of people who are exposed to C. jejuni do

not develop GBS which is associated with the pure motor axonal form of GBS (AMAN). He

further noted that some infections such as Epstein Barr, influenza A virus and cytomegalovirus,

which were not present in this case have been noted to have preceded GBS in some cases.

Importantly, he noted that cases of GBS have also been reported shortly after vaccination. He

referenced the rabies vaccine, the 1976 influenza vaccine, and the 2009 influenza vaccine which

showed 1.6 excess cases of GBS per 100,000 people.

Willison addressed AIDP (acute inflammatory demyelinating polyneuropathy), the type

of GBS that occurs most frequently in North America, and most likely the type that afflicted the

petitioner.

By contrast with acute motor axonal neuropathy, the immunological cascade

involved in acute inflammatory demyelinating polyneuropathy is less well

understood for various reasons. First, a wider range of immune stimulants cause

AIDP compared with AMAN, which includes bacteria and viral infections, and

vaccines. Second, biomarkers have yet to be characterized, despite widespread

screening efforts to identify the putative nerve antigens. At present a wider range

of anti-nerve autoantibodies directed at both proteins and glycolipids could be

responsible for AIDP immunopathology than is the case for AMAN or Miller

Fisher syndrome.

Id. Consistent with the state of knowledge about the cause of GBS, as explained by

Willison, Dr. Knobler essentially presented alternative theories as to the cause of the petitioner’s

GBS. These include bystander activation, which he referred to as the collateral damage theory,

and ultimately pointing to molecular mimicry as the most likely mechanism. Dr. Lee presented

the theory of molecular mimicry without using the term, by explaining the cross reaction of

antibodies stimulated by the immune response to the vaccine. Both agreed that molecular

mimicry or cross reaction triggered by the vaccine was the most likely mechanistic explanation

for the occurrence of the petitioner’s GBS eleven days after receipt of the Prevnar 13 vaccine.

Both pointed to the Haber article as finding 11 cases of post Prevnar GBS reported to VAERS

with mean time of onset of nine days and a range of two to 32 days.

While only the flu vaccine is presumed to be a cause of GBS in the Vaccine program,

petitioners have been found entitled to compensation for GBS caused by many other

vaccinations, including Prevnar 13. See 42 U.S.C. § 100.3(a). See e.g., Salmins v. Sec’y of Health

& Hum. Servs., No. 11-140V, 2014 WL 1569478 at *17 (Fed. Cl. Spec. Mstr. March 31, 2014)

(finding that the HPV vaccine can cause GBS); Peugh v. Sec’y of Health & Hum. Servs., No. 99-

638V, 2007 WL 15131666, at *17 (Fed. Cl. Spec. Mstr. May 8, 2007 (finding in an omnibus

proceeding that the hepatitis B vaccine can cause GBS); Whitener v. Sec’y of Health & Hum.

23

Servs., No. 06-0477V, 2009 WL 3007380, at * 20 (Fed. Cl. Spec. Mstr., Sept. 2, 2009) (finding

that the meningococcal vaccine caused GBS); Mohamad v. Sec’y of Health & Hum. Servs., No.

16-1075V, 2022 WL 711604, at *9-18 (Fed. Cl. Spec. Mstr. Jan 27, 2022) (finding that the Tdap

vaccine can cause GBS); J.G. v. Sec’y of Health & Human Servs., 2023 WL 2752634, at *29-32

(finding that the Hep A vaccine can cause GBS).

Importantly for this case, which was one of the early Prevnar/GBS cases tried, there have

now been multiple decisions by Special Masters finding that Prevnar was the cause of GBS

based on a theory of molecular mimicry. See, e.g., Koller v. Sec’y of Health & Hum. Servs., No.

16-439V, 2021 WL 5027947, at *7-20 (Fed. Cl. Spec. Mstr. Oct. 8, 2021 (finding that the

Prevnar 13 vaccine can cause GBS based on the mimicry between the essential phosphoglycerol

component of the vaccine with the polar head group in the phospholipid membrane in the myelin

of peripheral nerves.) (Gowen); Byrd v. Sec’y of Health & Human Servs., No. 20-1476, 2024 WL

4003061 at *21-26 (finding that molecular mimicry based on the CRM 197 conjugate satisfied

Althen 1) (Gowen). Similarly, other special masters have reached similar conclusions based on

substantially similar theories of molecular mimicry. See, e.g., Parker v. Sec’y of Health & Hum.

Servs., No. 20-411V, 2023 WL 9261248 (Fed. Cl. Spec. Mstr. Dec. 20, 2023) (Dorsey); Anderson

v. Sec’y of Health & Hum. Servs., No. 18-484V, 2024 WL 557052 (Fed. Cl. Spec. Mstr. Jan. 17,

2024) (Dorsey); Gross v. Sec’y of Health & Hum. Servs., No. 17-1075V, 2022 WL 9669651 (Fed.

Cl. Spec. Mstr. Sept. 22, 2022) (Dorsey); Sprenger v. Sec’y of Health & Hum. Servs., No. 18-

279V, 2023 WL 8543435 (Fed. Cl. Spec. Mstr. Nov. 14, 2023) (Dorsey); Maloney v. Sec’y of

Health & Hum. Servs., No. 19-1713V, 2022 WL 1074087 (Fed. Cl. Spec. Mstr. Mar. 17, 2022)

(Dorsey); Simeneta v. Sec’y of Health & Hum. Servs., No. 18-1859V, 2024 WL 4881411 (Fed.

Cl. Spec. Mstr. Oct. 31, 2024 (Dorsey); Pierson v. Sec’y of Health & Hum. Servs., No. 17-1136V,

2022 WL 322836 (Fed. Cl. Spec. Mstr. Jan. 19, 2022) (Horner); Bartoszek v. Sec’y of Health &

Hum. Servs., No. 17-1254V, 2024 WL 4263604 (Fed. Cl. Spec. Mstr. Aug. 27, 2024) (Horner);

Cooper v. Sec’y of Health & Hum. Servs., No. 18-1885V, 2024 WL 1522331 (Fed. Cl. Spec.

Mstr. Mar. 12, 2024) (Horner); Tracy v. Sec'y of Health & Human Servs., No. 16-213V, 2022 WL

1125281, at *29-32 (Fed. Cl. Spec. Mstr. Mar. 30, 2022) (Sanders).

Some of these cases also accepted the theory of mimicry between the CRM197 protein in

Prevnar with various nodal or paranodal components of the peripheral nerves either together with

the phosphoglycerol theory or standing by itself as a likely source of GBS causing molecular

mimicry. 16 See e.g., Byrd, No. 20-1476, 2024 WL 4003061 at *21-26. I have considered the

16

Acceptance of this theory has not been unanimous among special masters. Deshler v. Sec’y of Health & Hum.

Servs., No. 16-1070V, 2020 WL 4593162 (Fed. Cl. Spec. Mstr. July 1, 2020) (Corcoran); Trollinger v. Sec’y of

Health & Hum. Servs., No. 16-473V, 2023 WL 2521912, at *26-31 (Fed. Cl. Spec. Mstr. Feb. 17, 2023) (Corcoran);

Bialek v. Sec'y of Health & Hum. Servs., No. 18-761V, 2023 WL 35509, at *33-37 (Fed. Cl. Spec. Mstr. Jan. 3,

2023) (Corcoran); Gamboa-Avila v. Sec'y of Health & Hum. Servs., No. 18-925V, 2023 WL 6536207 (Fed. Cl.

Spec. Mstr. Sept. 11, 2023) (Corcoran), mot. rev. den'd, No.18-925V (Fed. Cl. filed Feb. 26, 2024); McConnell v.

Sec’y of Health & Hum. Servs., No. 18-1051, 2022 WL 4008238 (Fed. Cl. Spec. Mstr. Aug. 19, 2022) (Moran);

Crosby v. Sec’y of Health & Hum. Servs., No. 18-1478V, 2021 WL 3464125 (Fed. Cl. Spec. Mstr. July 22, 2021)

(Moran); Morrison v. Sec’y of Health & Hum. Servs., No. 18-386V, 2024 WL 3738934 (Fed. Cl. Spec. Mstr. July

18, 2024) (Oler)

24

reasoning in these cases and consistent, with my prior opinions find the decisions favoring

causation to be persuasive.

Petitioner presented the testimony of two physician experts and a third by an expert

report. The third, Dr. Robert Hyzy, M.D. did little more than point to the post Prevnar GBS cases

reported in the Haber study referenced above and opined that the timing of onset ten to eleven

days after vaccination was sufficient to prove causation. He did not present a theory of

pathogenesis and his opinion was almost entirely based on the cases reported in Haber and the

temporal relationship between the vaccination and the onset of symptoms. While timing is an

important consideration in evaluating causation it has never been sufficient to prove causation

standing by itself. The cases reported to VAERS as detailed in Haber raise the issue of causation

but do not explain it. Therefore, Dr. Hyzy’s opinion is accorded little weight as to Althen prong

one.

Dr. Knobler began his testimony with a general explanation of how vaccines, including

the Prevnar vaccine work. He testified that the Prevnar vaccine contains strains of the

“pneumococcus bacteria and components of them that stimulate the immune system in order to

provide a level of protection against infection with these.” Tr. 123. As to vaccines generally, Dr.

Knobler explained that the purpose of vaccines “is to stimulate the immune system.” The

immune system is stimulated by a “combination of a number of different strains of bacteria”

which provide “an immune response in order to provide protection from the actual bacteria.” Id.

In some susceptible individuals, however, “that stimulation of the immune system can lead to

development of Guillain Barre” due to a misdirection of the immune response which “can lead to

loss of tissue.” Id. at 124-25.

At the entitlement hearing, Dr. Knobler testified that autoimmune diseases are common,

that the tolerance system that Dr. He discussed is not infallible, and that the process of the

development of an autoimmune disease such as GBS is multi-factorial. He said that autoimmune

diseases are a reflection of the genetic background of the individual, interaction with an

environmental agent – such as a vaccine – and the activation of the immune system. Tr. 196-97.

He said that there is a certain amount of time in which the immune system is responsive to a

particular stimulant and, in the case of petitioner, the timeline of 10-11 days between the

administration of the Prevnar vaccine and the onset of her neurological symptoms fit most

closely and more so than that with a possible URI occurring three to five days prior to onset. Id.

at 198.

Dr. Knobler explained at the hearing that there are “a number of different mechanisms

that have been investigated” for how vaccines can cause GBS, one being molecular mimicry and

another which he referred to as “collateral damage.” Tr. 127. Respondent, in his post-hearing

brief, argued that Dr. Knobler’s testimony regarding molecular mimicry was contradictory to his

initial theory. Resp’t Post Hearing Brief (ECF No. 106). During the initial hearing, Dr. Knobler

testified that he believed “that collateral damage more likely than molecular mimicry is the

responsible mechanism.” Id. at 148. His use of the term “collateral damage” seemed to describe a

result more than a theory, but in his explanation of it, as noted by Dr. He, it appeared that he was

describing bystander activation, which is also one of the primary theories of autoimmune

25

causation. Dr. Knobler was asked to clarify this, and he testified that bystander activation occurs

when the immune response, which includes inflammation, is greater than what was intended by

the immune stimulation by a specific antigen such as in a vaccine. Id. at 204. He said that the

immune response varies from person to person, and, in the vast majority of people, we see a very

specific immune response directed against a very targeted antigen in order to achieve the desired

effect. However, some people are high responders. In some people, the impact of the agents in

the vaccine go beyond the intended result and that is where we get into problems such as the

occurrence of GBS when an individual has a broad response based on the capacity of their

immune system to respond. This explains how the bystander effect is capable of causing an

unintended result when stimulated. Id. at 205-07. Dr. Knobler noted that collateral damage or

bystander activation is the result of the immune system being keyed up or turned on. Id. at 147.

He also noted that this hypothesis does not require a specific antigen and instead only needs

stimulation of the immune system which occurs when a stimulant acts to juice up or amplify the

response that the immune system is capable of making in a susceptible individual. Id. at 147-48.

In this case, he opined that the Prevnar vaccine served as the immune stimulant that generated

the strong immune response in the petitioner. Id. at 148. He stated that, “In neurology…we refer

to the damage that we see as the final common pathway, and that there are multiple ways in

which you can reach the damage that you see. In GBS, the final common pathway is the damage

to the myelin that occurs at the nerve roots.” Id. at 168.

Bystander activation has been recognized in other cases in the program. For example, in

Henley v. Sec’y of Health and Human Services, Special Master Roth wrote:

Another viable mechanism is bystander activation, which occurs when there is an

exaggerated immune response to an exogenous agent that induces local tissue

inflammation and stimulation of otherwise unaffected normal cells which can

result in the release of normally sequestered self-antigens. The inflammation may

activate previously dormant auto-reactive Th-1 cells that then react against the

newly released self-antigens. Bystander activation cannot be seen clinically, but it

is a mechanistic component of the process that triggers (autoimmune disease)

No. 16-499V, 2024 WL 2272670 at *26 (Fed. Cl. Spec. Mstr. Apr. 25, 2024).

Indeed, bystander activation can act in conjunction with molecular mimicry as noted in

Cooper, another Prevnar/GBS case in which Special Master Horner observed that Dr. Latov

invoked both molecular mimicry and bystander activation, specifically noting that the two

mechanisms can operate in conjunction. Cooper, No. 18-1885V, 2024 WL 1522331, at *13.

As to the molecular mimicry aspect of petitioner’s theory specifically, prior to the

entitlement hearing, Dr. Knobler provided an expert report in which he opined on causation as

follows:

26

Development of GBS is an unfortunate occurrence, it is a serious, potentially life-

threatening disease. The precise mechanism by which it is caused has not yet been

fully clarified. However, one of the mechanisms proposed in some forms of GBS

has been that of molecular mimicry, in which either the precise sequence or overall

structure of a host cell and infectious agent coincide. GBS has been reported,

(Khatib) for the pneumococcal pneumonia infection. Pet’r Ex. 12 at 5

At the continuation of the hearing, Dr. Knobler focused on molecular mimicry and testified that,

based on his laboratory experience and his understanding of the literature, molecular mimicry

more likely than not “played a role in causation with respect to the vaccine.” Tr. 219. He said that

molecular mimicry with the Prevnar vaccine was the most likely mechanism of causation of

petitioner’s GBS. Id. As noted above, molecular mimicry and bystander activation mechanisms

are not mutually exclusive and either may lead to “collateral damage” when there is a failure of

tolerance.

Dr. Knobler testified that in GBS, an antibody binds to tissue, which then

activates and recruits macrophages, and the macrophages damage the tissue the antibody

is attached to. Tr. 126. Dr. Knobler described the mechanism, stating:

And once the immune system is stimulated to react to that [antigen], you

then get antibodies produced, you get activated cells of the immune

system…there are helper cells that allow the antibody producing cells to

function and give antibody producing cells a green light to function and

that triggers the sequence of events that could yield to the demyelination.

Tr. 128-29. To support his theory, Dr. Knobler primarily relied on an article by Yuki, which

described the pathogenesis of GBS. Tr. 151; Pet’r Ex. 12.5. Specifically, Dr. Knobler referred to

a paragraph in that article which reads:

The classic pathological findings in acute inflammatory demyelinating

polyneuropathy are inflammatory infiltrates (consisting mainly of T cells and

macrophages) and areas of segmental demyelination, often associated with signs

of secondary axonal degeneration, which can be detected in the spinal roots, as

well as in the large and small motor and sensory nerves. There is evidence of

early complement activation, which is based on an antibody binding to the outer

surface of the Schwann cell and deposition of activated complement components;

such complement activation appears to initiate the vesiculation of myelin.

Macrophage invasion is observed within 1 week after complement-mediated

myelin damage occurs.

Pet’r Ex. 12.5 at 4. The Yuki article also explains that:

[A]utoantibodies may bind to myelin antigens and activate complement. This is

followed by the formation of a membrane-attack complex (MAC) on the outer

27

surface of Schwann cells and the initiation of vesicular degeneration.

Macrophages subsequently invade myelin and act as scavengers to remove myelin

debris…Myelinated axons are divided into four functional regions: the nodes of

Ranvier, paranodes, juxtaparanodes, and internodes. Gangliosides GM1 and

GD1a are strongly expressed at the nodes of Ranvier, where the voltage-gated

sodium (Nav) channels are localized. Contactin-associated protein (Caspr) and

voltage-gated potassium (Kv) channels are respectively present at the paranodes

and juxtaparanodes. IgG anti-GM1 or anti-GD1a autoantibodies bind to the nodal

axolemma, leading to MAC formation. This results in the disappearance of Nav

clusters and the detachment of paranodal myelin, which can lead to nerve-

conduction failure and muscle weakness. Axonal degeneration may follow at a

later stage. Macrophages subsequently invade from the nodes into the periaxonal

space, scavenging the injured axons.

Pet’r Ex. 12.5 at 5. Notably, one reason why autoantibodies would bind to myelin

antigens or to the outer surface of the Schwann cells, as discussed by Yuki, is through molecular

mimicry. As Dr. Knobler explained, a vaccine can cause GBS via molecular mimicry and

subsequently through the process described by Yuki because “there can be components in a

vaccine…in which…either the sequence or structure resembles a sequence or structure within the

body. And so the immune system response that is being stimulated by that vaccine is then going

to target a comparable sequence or structure in the individual.” Tr. at 213. Dr. Knobler further

testified that molecular mimicry “has been documented in humans to exist where either the

specific sequence of a substance or the shape of a substance provides stimulation to the immune

system, and that allows recognition of a target on an individual…such as the myelin sheath in a

disease like GBS…” Id. at 128. Dr. Knobler noted that “once the immune system is stimulated to

react to that, you then get antibodies produced, you get activated cells of the immune system…”

including “helper cells that allow the antibody-producing cells to function…” which “triggers the

sequence of events that could yield the demyelination.” Id. at 129. He further explained that his

proposed molecular mimicry theory could be described as an immune response directed against

target antigens of potential agents that may cross-react with molecules in the nervous system. Id.

at 358. Such molecules would be those in the outer surface of the Schwann cells or myelin

antigens, as described by Yuki.

This is consistent with Dr. Lee’s explanation of molecular mimicry, in which he

explained that the Prevnar 13 vaccine causes GBS “through the immune response generated by

the vaccine,” and that this immune response is to “look for road signs.” Id. at 79. He explained

that, typically, these “road signs are on the bacteria,” but “the nerve cells in the body also have

similar road signs.” Id. In this case, “the body can’t tell the difference whether the road sign…is

on the nerve or on the bacteria. So that’s how the nerve cells are attacked by the body’s immune

system through that immune response created by the vaccine.” Id. at 80. He defined “road signs”

as “the epitope proteins which are proteins on the surface of the bacteria, but also on the surface

of the human cells.” Id. at 80-81. Thus, “if those epitopes are similar between a bacteria and

28

nerve cells, then the immune system will also attack the nerve cells that have similar epitopes as

the bacteria.” Id. at 81.

Dr. Knobler explained that after the cross reaction between antigens in the vaccine and

components of peripheral nerve occurs, the Fc portion of the antibodies provides a point of

attachment for the invasion of macrophages and complement which cause damage to the cells,

which Dr. Knobler termed “collateral damage,” leading to GBS. Although Yuki did not

specifically discuss vaccine causation this mechanism is consistent with his biological

description of what Dr. Knobler opined is thought to occur in GBS after a vaccination.

Both Dr. Knobler and Dr. Lee referred to the Haber article to support their molecular

mimicry theories. Tr. 82, 142-45; Pet’r Ex. 9.2. This article is a vaccine reporting administration

post-licensure surveillance report to evaluate the safety of the PCV 13 vaccine. Id. at 1. Dr. Lee

observed that the study found that “in persons over the age of 65 that received the Prevnar 13,

there were 10 to 11 cases reported for GBS.” Tr. 82. The study noted 11 verified reports of GBS

“with symptom onset within 42 days of PCV vaccination with a reporting rate of 0.7 cases per

million doses of vaccine distributed among adults aged” 19 or older. Pet’r Ex. 9.2 at 5. More

specifically, the “median onset interval of symptoms” for these 11 cases was 9 days, with a range

of 2-34 days after the vaccination, and the median age was 68 years with a range of 56-88. Id.

Despite these findings, the authors concluded that the “data mining analysis identified no

disproportionate reporting for GBS.” Id.

Respondent’s experts, Dr. He and Dr. Callaghan also noted that the authors of the Haber

article, despite discussing 11 cases of post Prevnar GBS as reported to VAERS, concluded that

this many cases were not sufficient to constitute a signal of a potential adverse event. See Tr. 264,

324-25. While Haber concluded that these cases did not identify a new safety signal, the fact that

11 cases of GBS within 42 days following vaccination with Prevnar 13 were identified

nevertheless provides some circumstantial evidence of causation much as case reports do. For

example, the article by Ravishankar reported in detail on a case of GBS following the

administration of the Prevnar vaccine. See Pet’r Ex. 12.3. Moreover, as noted by other special

masters, though Haber found “no disproportionate reporting for GBS,” articles, such as Haber,

which rely on VAERS data “are subject to significant limitations.” Pierson, 2022 WL 322836, at

*30; Pet’r Ex. 9.2. Notably, the Haber authors caution that the “limitations of VAERS…may

include underreporting, varying quality of reports…and the lack of an unvaccinated comparison

group.” Pet’r Ex. 9.2 at 5. Haber also notes that such limitations make it “extremely difficult to

determine causal associations between vaccines and” adverse events. Id. Perhaps more important

than the number of VAERS reports found by the Haber authors in this 2016 article, is the fact

that far more Prevnar/GBS cases with detailed records have been filed in the Vaccine Program.

In fact, to date, there have been more reasoned decisions in the Vaccine Program than there were

cases were found by Haber and there are many more cases pending on the docket. As an

indication of the underreporting problem with VAERS data most cases filed in the Vaccine

Program do not have filed VAERS reports.

29

Dr. He proposed three primary criticisms of the theories of Dr. Knobler and Dr. Lee. First,

he contended that Prevnar was a weak vaccine, second that the tolerance system prevents

autoimmune disease by training our immune cells not to attack self, and third that Dr. Knobler

and Dr. Lee failed to provide a sophisticated discussion of immune mechanisms including Toll

Like Receptors (TLRs), dendritic cells, C-lectin, PAMPS and DAMPS. 17 He also argued that the

breadth of the immune response to a wild infection is much greater than to the components of a

vaccine.

While Dr. He testified that Prevnar 13 was a weak vaccine, he did not explain why it

would be considered weaker than other vaccines. In fact, the Sanford study 18 filed by the

respondent detailing various comparative studies, described that Prevnar contains 12 serotypes in

common with the Pneumococcal 23 vaccine and that Prevnar 13 provoked “a significantly

greater immune response than PPV23 for 8 of 12 serotypes in common.” Resp’t Ex. G-7 at 5, 12.

Dr. He testified that the Prevnar vaccine was “relatively weak” because it “contains very simple

components” including “one type of PAMP called polysaccharide and a carrier protein…from

diphtheria serum 1.” Tr. 249. Despite this statement, Dr. He also agreed that the diphtheria

protein conjugate and adjuvant in the Prevnar vaccine stimulate a more aggressive immune

response than the PPV23 and may play a role in macrophage activation. Id. at 250. As Sanford

reported the immune response to the conjugated vaccine with an adjuvant appears to be

considerably stronger than the response to the PPV23 which does not contain CRM197 (the

diphtheria carrier protein) or an adjuvant both of which were added to increase the immune

response to the vaccine. Resp’t Ex. C-7 at 12. An article by Pulendran and Ahmed entitled

Immunological mechanisms of vaccination, 19 notes that vaccines such as the polysaccharide

vaccine conjugated with the diphtheria antigen contains an adjuvant, alum, which has been

shown to induce antibody responses independent of TLRs. Resp’t Ex. G-3 at 3. Furthermore, the

authors say, alum exerts a direct effect on IL-4 producing Gr-1 cells that are essential for priming

and cloning expansion and optimal antibody production by B cells in vivo. Id. Thus, it would

appear that the combination of the lipopolysaccharides (which also have an essential

phosphoglycerol sidechain) combined with CRM 197 and the alum adjuvant has resulted in a

considerably stronger vaccine than the prior pneumococcal vaccine which had been effective

with adults.

While the role of tolerance in preventing attacks on self-antigens or structures is well

recognized in general, Dr. He agreed that when a person develops an autoimmune disease such

as GBS then the tolerance system has failed. Tr. 248. Thus, it follows that, as petitioner clearly

developed a severe case of GBS, the tolerance and regulatory checkpoints, while important

counterforces in general, failed in her case. While Dr. He testified that there is no such term as

PAMPS stands for pathogen associated molecular patterns. DAMPS stander for danger or damage associated

17

molecular patterns which are recognized by immune cells such as dendritic cells or TLRs.

18

Mark Sanford, Pneumococcal Polysaccharide Conjugate Vaccine (13-Valent, Adsorbed), 72 Adis Drug Profile

(2012).

19

Bali Pulendran & Rafi Ahmed, Immunological mechanisms of vaccination, 12 Nature Immunology 509 (2011).

30

collateral damage in immunology, the concept was recognized in an article he submitted. Tr. 233.

The article by Wykes and Lewin, 20 filed by Dr. He, discussing immune checkpoint molecules,

notes that such molecules “are crucial for maintaining self-tolerance and for modulating the

length and magnitude of effector immune responses in peripheral tissues to minimize collateral

tissue damage.” Resp’t Ex. G-2 at 1 (emphasis added). While I agree that the term collateral

damage, as used by Dr. Knobler, immunologically was better understood to be describing

bystander activation, the Wykes article recognizes the notion of collateral damage as a result to

be avoided through the regulatory and tolerance systems. The collateral damage in this case was

the resulting GBS when the tolerance and checkpoint systems did not work to prevent a cross

reactive autoimmune attack in this particular patient.

Importantly, Dr. He acknowledged that the occurrence of GBS necessitates the breaking

of tolerance or the control mechanisms of the immune system. Id. at 283. Dr. He testified that “if

the control means work properly…you will not get GBS.” Moreover, Dr. He agreed that if there

is “a component in the [Prevnar 13] vaccine that cross-reacts with something in the Schwann

cells or in the myelin, whether it’s a strong vaccine or a weak vaccine, autoimmunity could occur

in someone who [is] genetically susceptible and [in whom] tolerance breaks down.” Id. at 259.

I agree that the explanation of molecular mimicry provided by petitioner’s experts in this

case was not as sophisticated as theories presented in other cases. However, the explanation from

petitioner’s experts is consistent with that of Willison who indicated that molecular mimicry is

likely a significant mechanism in the development of GBS, but that the specific antigens in

question are not well understood to date except in the case of C. jejuni in the AMAN form of

GBS. Willison emphasized that in AIDP there is a larger list of likely mimics whether the

foreign antigen is an infection or a vaccine. In the Vaccine Program the Federal Circuit, as noted

above, has held that the petitioner is not required to provide a detailed biological explanation as

long as she provides a sound and reliable theory. Moreover, petitioner may satisfy the first

Althen prong without resort to medical literature, epidemiological studies, demonstration of a

specific mechanism, or a generally accepted medical theory. Andreu, 569 F.3d at 1378-79 (citing

Capizzano, 440 F.3d at 1325-26). The theory provided in this case invoked two well recognized

theories of autoimmunity – molecular mimicry and bystander activation – supported by the

appropriate timing of the immune response to the vaccine. Dr. He also agreed that the

petitioner’s checkpoint or tolerance system had failed as evidenced by the onset of GBS, and that

in a genetically susceptible person an element of a vaccine could cross react with the myelin in

the peripheral nerves and cause GBS.

While Dr. He and Dr. Callaghan propose a standard of proof requiring medical literature

showing direct biological evidence of the mechanism of autoimmunity linking the Prevnar 13

vaccine to GBS, the Federal Circuit has held that requiring medical literature directly on point

“contravenes section 300aa-13(a)(1)’s allowing medical opinion as proof. [Requiring specific

medical literature] prevents use of circumstantial evidence envisioned by the preponderance

20

Michelle Wykes & Sharon Lewin, Immune checkpoint blockade in infectious disease, 18 Immunology 91, 91

(2018).

31

standard…” Althen, 418 F.3d at 1280. Scientific certainty or biological specificity, the standard

applied by Dr. He and Dr. Callaghan, is not petitioner’s burden of proof in the Vaccine Program,

particularly when the state of medical knowledge is not sufficient to provide such specificity. As

held by the Federal Circuit in Althen, “While this case involves the possible link between TT

vaccination and central nervous system injury, a sequence hitherto unproven in medicine, the

purpose of the Vaccine Act’s preponderance standard is to allow the finding of causation in a

field bereft of complete and direct proof of how vaccines affect the human body.” Althen, 418

F3d 1274 at 1280.

Molecular mimicry has been accepted in numerous program cases as a cause of GBS.

Multiple cases have also found molecular mimicry in the immune response to the Prevnar

vaccine to be the cause of GBS. See, inter alia, Koller, Anderson, Gross, Pierson, Cooper,

Bartoszek, Byrd, supra p. 24. “In fact, given the nature of the condition, molecular mimicry has

been accepted as a theory of causation for GBS even in the absence of any demonstration of

homology and cross-reaction.” Salmins, 2014 WL 1569478 at *14; Bartoszek, 2024 WL

4263604, at *16.

Petitioner’s theory that the Prevnar 13 vaccine can act as an immune stimulant causing

molecular mimicry, leading to cell damage and GBS is sound and reliable and is consistent with

the holdings in multiple other cases involving Prevnar and GBS, as detailed above. The

respondent’s experts do not dispute that the Prevnar 13 vaccine is an immune stimulant.

Moreover, they do not dispute that cross-reactions may happen particularly in genetically

susceptible individuals. The medical literature provided by both parties explained the process by

which damage can occur leading to GBS while recognizing that the field is bereft of complete

and direct proof of how vaccines or infections cause GBS. Petitioner has presented a theory of

molecular mimicry and or bystander activation which has been recognized and accepted as a

sound and reliable theory in Prevnar/GBS cases as well as in the cases of other vaccines and

GBS. Petitioner is not required to provide proof of specific epitopes or proven biological

mechanisms to satisfy prong one. Although articles, such as Haber, cited by petitioner’s experts

have limitations, I find that after consideration of all the evidence presented in this case,

including the expert reports, expert testimony, and medical literature filed, I find that petitioner

has provided preponderant evidence of a sound and reliable medical theory and has satisfied

Althen Prong one.

b. Althen Prong Two

To satisfy Althen prong two, petitioner must show by a preponderance of the evidence

that there was a “logical sequence of cause and effect showing that the vaccine was the reason

for the injury.” Capizzano, 440 F.3d at 1324 (quoting Althen, 418 F.3d at 1278). “Petitioner must

show that the vaccine was the but for cause of the harm…or in other words, that the vaccine was

the ‘reason for the injury.’” Pafford, 451 F.3d at 1356. In evaluating whether this prong is

satisfied, the opinion and views of treating physicians are entitled to some weight. Andreu, 569

F.3d at 1367; Capizzano, 440 F.3d at 1326. Medical records and medical testimony are favored

in vaccine cases, as treating physicians are likely to be in the best position to determine whether

32

there is a logical sequence of cause and effect. Althen, 418 F.3d at 1280; see also Capizzano, 440

F.3d at 1326. The petitioner need not make a specific type of evidentiary showing, i.e.,

“epidemiologic studies, rechallenge, the presence of pathological markers or genetic

predisposition, or general acceptance in the medical community to establish a logical sequence of

cause and effect.” Capizzano, 440 F.3d at 1325. Petitioner may satisfy her burden by presenting

circumstantial evidence and reliable medical opinions. Id.

As I previously concluded that petitioner has satisfied Althen prong one, the analysis next

turns to whether the Prevnar 13 vaccine petitioner received caused her GBS. Performing such

inquiry requires analysis of the appropriateness of the diagnosis, the course of petitioner’s illness,

and the logic of the explanation building upon the conclusion under Althen prong one that the

vaccine can cause GBS. In this case, all experts agreed that petitioner was appropriately

diagnosed with GBS and that her symptoms began about 11 days after her vaccination. There

was, however, disagreement among the experts as to whether an upper respiratory infection

(“URI”) alternatively caused petitioner’s GBS. While respondent may present evidence relating

to an alternative cause to demonstrate the inadequacy of petitioner’s evidence supporting her

case in chief, petitioners are not required to eliminate alternative causes “where the other

evidence on causation is sufficient to establish a prima facie case.” Walther v. Sec’y of Health &

Hum. Servs., 485 F.3d 1146, 150 (Fed. Cir. 2007); de Bazan v. Sec’y of Health & Hum. Servs.,

539 F.3d 1347, 1353 (Fed. Cir. 2008).

The fact that petitioner has satisfied Althen prongs one and three (as will be discussed

below) is significant to the Althen prong two analysis. See Capizzano, 440 F.3d at 1326. Both of

petitioner’s experts opined that there was a logical sequence of cause and effect between

petitioner’s vaccination and the development of GBS. Dr. Lee testified that “the temporal nature

of the vaccine administration as well as the development of symptoms” provided evidence of

such logical sequence. Tr. 83. He further explained that, in the Haber study, “the reported time

frame for the development of GBS after Prevnar was 2 to [42] [sic] days, average being 9. In

[petitioner’s] case, it was 11 days, so within that timeframe.” Id. Moreover, Dr. Lee’s expert

report notes that “Vaccines are antigenic stimuli and are associated with GBS. Administration of

Prevnar-13 to [petitioner] was directly causal to her development of GBS. Were it not but for the

administration of Prevnar-13, [petitioner] would not have developed GBS.” Pet’r Ex. 11 at 5. Dr.

Knobler similarly testified that the fact that onset occurred within 11 days of the vaccination and

that, in his opinion, there were no alternative explanations for petitioner’s GBS creates a logical

sequence of cause and effect.

The cause of GBS within this time frame is well supported by the mechanism of

molecular mimicry or bystander activation in that program cases have frequently recognized a

time frame including eleven days to be an appropriate interval for the onset of GBS caused by a

cross reaction stimulated by the vaccine. Thus, while the petitioner’s experts pointed heavily to

the timing of the onset in relation to receipt of the Prevnar vaccine, when understood in terms of

the time in which a cross reaction caused by molecular mimicry can occur it is sufficient to

demonstrate a logical sequence of cause and effect between the vaccine and the petitioner’s GBS.

33

Petitioner’s medical record likewise support a logical sequence of cause and effect

between the vaccination she received and her GBS. Petitioner received the Prevnar 13 vaccine on

July 11, 2016. Twelve days later, she presented to the ED with complaints of numbness and

tingling in her hands and feet starting the night before. Pet’r Ex. 3 at 57, 60. Her treating

providers immediately noted that she received the Prevnar vaccine prior to the onset of her

symptoms. Her treating providers also consistently listed the vaccine as a potential cause of her

GBS along with a preceding URI.

Most of Dr. Callaghan’s testimony addressed the issue of a possible URI in the petitioner

prior to the onset of GBS. He argued that an upper respiratory infection is statistically more

likely to be a cause of GBS. I will address his opinion in detail under “alternative cause” below.

Dr. He agreed that there would have been an active immune response to the vaccine ten

to eleven days after vaccination and if the petitioner had a URI there would also have been an

immune response to that three or four days after onset. He agreed that the combined effect of the

immune response to the vaccine and to a possible URI could have caused an overwhelming

immune response leading to her GBS. Tr. 312-13. Thus, even if she did have an upper

respiratory infection, the evidence for which, as addressed below, is equivocal, the combined

immune response to the vaccine and to an infection could have combined as substantial factors in

causing the petitioner to develop GBS. See, Shyface, 165 F.3d at 1352-53.

Where there is conflicting evidence in the record which neither compels nor precludes a

finding of viral alternate causation, then compensation must be awarded. Knudsen, 35 F.3d at

550. As will be addressed below, I have concluded that the evidence does not establish that a

virus acted as the sole cause of the petitioner’s GBS.

With diagnosis and onset established and undisputed and the evidence for a URI being at

best equivocal, the fact that petitioner has satisfied Althen prongs one and three is significant to

the Althen prong two analysis. See Capizzano, 440 F.3d at 1326. The progression from

vaccination to onset of GBS in 11 days as caused by molecular mimicry or bystander activation

is logical based on the general understanding of immune cross reactivity. It is reinforced by the

timing of onset found by Haber of 2-42 days with a median of nine days. The petitioner’s onset

was quite close to the median of this range.

The testimony and reports of petitioner’s experts, and the repeated notations by

petitioner’s treating providers that the vaccine was a potential cause of her GBS, provide

preponderant evidence of a logical cause and effect between the Prevnar vaccine and the

affliction of the petitioner with GBS. Therefore, I find that petitioner has shown preponderant

evidence of a logical sequence of cause and effect between the vaccination and her injury, and

has thus, met her burden under Althen prong two.

c. Althen Prong Three

Althen prong three requires petitioner to establish a “proximate temporal relationship”

between the vaccination and the injury alleged. Althen, 418 F.3d at 1281. This phrase is further

defined as a “medically acceptable temporal relationship.” Id. A petitioner must offer

34

“preponderant proof that the onset of symptoms occurred within a timeframe for which, given

the medical understating of the disorder’s etiology, it is medically acceptable to infer causation-

in-fact.” de Bazan, 539 F.3d at 1352. Although a temporal association alone is insufficient to

establish causation, under the third prong of Althen, a petitioner must show that the timing of the

injury fits with the causal theory. See Althen, 418 F.3d at 1278. The special master cannot infer

causation from temporal proximity alone. Thibaudeau v. Sec’y of Health & Hum. Servs., 24 Cl.

Ct. 400, 403-04 (1991); see also Grant v. Sec’y of Health & Hum. Servs., 956 F.2d 1144 (Fed.

Cir. 1992) (“[T]he inoculation is not the cause of every event that occurs within the ten-day

period…[w]ithout more, this proximate temporal relationship will not support a finding of

causation.”).

Dr. Knobler noted in his report that “the time period between the vaccination and the onset of

symptoms (July 22, 2016) was noted as 11 days.” Pet’r Ex. 12 at 3. There is in fact no dispute

that petitioner received the Prevnar 13 vaccine on July 11, 2016 and developed the initial

symptoms of GBS on the evening of July 22. These symptoms developed rapidly into full blown

GBS through the day of July 23 and resulted in a prolonged hospitalization/inpatient

rehabilitation and significant disability. The fact that petitioner’s onset of GBS occurred 11 days

after vaccination was not contested by respondent’s experts. Dr. Callaghan, in his report and his

testimony, indicated that petitioner “developed GBS 11 days after [the] Prevnar vaccination and

8 days after an upper respiratory infection.” Resp’t Ex. A at 1. Such timing from vaccination to

onset of symptoms is also consistent with petitioner’s testimony and medical records. The

medical records indicate that petitioner received the Prevnar 13 vaccine on July 11, 2016. Pet’r

Ex. 2 at 15. Petitioner testified that, about a day later, her arm became sore, “was very red,” and

“looked kind of crusty at the injection site.” Petitioner’s husband described the area as about

“two inches long by an inch wide with redness.” Id. at 32. About 11 days after vaccination, on

July 22, 2016, petitioner was “feeling good” but had “tingling in her hands and feet.” Id. at 52-

53. By the next morning, petitioner was unable to move, and Mr. Diponziano called 911.

Petitioner was taken to the Cooper University Hospital Emergency Department complaining of

numbness and tingling beginning at about 10:00 p.m. the previous night “with progressive severe

weakness.” Pet’r Ex. 3 at 57, 60. Based on this record, petitioner’s onset occurred on July 22,

2016, or 11 days after she received the Prevnar vaccine.

During the entitlement hearing, Dr. Lee testified that the onset of symptoms 11 days after

the vaccination fits with petitioner’s theory because “the administration of the vaccine and then

the time for the body to react and have that immune response where it’s producing the antibody

to make the vaccine…takes time and [is] different from individual to individual.” Tr. 83-84. In

petitioner’s case, “11 days is the time that it took her body to generate the immune response and

for those antibodies to attack the epitopes on her nerve cells.” Id. at 84. Dr. Lee referred to the

Haber article to support his opinion that such timeline is appropriate, noting that the reported

timeframe in the study “for the development of GBS after Prevnar was 2 to 42 days, [with the]

average being 9.” Tr. 83. Dr. Knobler similarly testified that 11 days from vaccination to onset of

petitioner’s GBS “is within the expected time course for such events to occur.” Tr. 130.

An onset of GBS 11 days after vaccination is also consistent with what has been found to

be appropriate timing in other cases in the Vaccine Program in which molecular mimicry is the

causal theory for Prevnar vaccine causation of GBS. See e.g., Koller, 2021 WL 5027947 at *23

35

(finding that onset of GBS 12 to 14 days after receipt of the Prevnar-13 vaccine was “an

acceptable timeframe in which to infer causation.”); Byrd v. Sec’y of Health & Hum. Servs., No.

20-1476V, 2024 WL 4003061, at *28-29 (Fed. Cl. Spec. Mstr. July 8, 2024) (accepting onset

about four days after receipt of the Prevnar vaccine as a medically appropriate timeframe);

Anderson, 2024 WL 557052, at *34 (finding onset of 10 days to be appropriate.).

Based on petitioner’s medical records, the expert reports, medical literature, and the

expert testimony, I find that petitioner has presented preponderant evidence that petitioner’s

onset of GBS occurred 11 days after her Prevnar vaccination and that such timing is medically

acceptable and fits with petitioner’s causal theory of molecular mimicry. Thus, petitioner has

preponderantly established a “proximate temporal relationship” between the vaccination and her

injury and has satisfied Althen prong three. As such petitioner has established a prima facie case

of vaccine causation.

d. Alternative Cause

Respondent’s expert, Dr. Callaghan, opined that petitioner had a preceding URI that was

the more likely cause of her GBS as opposed to the Prevnar vaccine. Dr. Callaghan testified that

GBS can be a post-infectious condition, meaning “that infections can trigger the immune system

to cause patients to have GBS.” Id. at 321. This occurs “mostly with upper respiratory tract

infections and gastrointestinal illnesses, particularly Campylobacter” which the petitioner did not

have. Id. He stated that when GBS is suspected to be secondary to an infection, the antecedent

infection is “very rarely identified” and is not looked for with URIs. Id at 321-22. Dr. Callaghan

testified that, to determine whether a patient’s GBS is post-infectious, one looks to “whether

there is medical evidence” and “if someone has a temporal association.” Id. at 322. According to

Dr. Callaghan, a URI within “a handful of weeks of the” onset of GBS would lead to the

conclusion that the GBS is post-infectious.

In order to establish alternate causation, once petitioner has satisfied the three Althen

prongs, the government must provide “proof that some other factor was the actual cause…by

identifying a particular such factor (or factors) and presenting sufficient evidence to establish

that it was the sole substantial factor in bringing about the injury.” de Bazan v. Sec’y of Health &

Hum. Servs., 539 F.3d 1347, 1354 (Fed. Cir. 2008)(emphasis added). While true that respondent

need not identify a specific type of viral infection to establish alternate causation, if conflicting

evidence on the record neither compels nor precludes a finding of alternate causation, then “the

government has failed in its burden and compensation must be awarded.” Andreu, 569 F.3d at

1378 (citing Knudsen, 35 F.3d at 550). Moreover, where there are two potential causes for an

illness, a petitioner is not required to eliminate the other potential cause in order to be entitled to

compensation. Walther v. Sec’y of Health & Hum. Servs., 485 F.3d 1146, 1150 (Fed. Cir. 2007)

(ruling that “Petitioner does not bear the burden of eliminating alternative independent potential

causes.”); Pafford, 451 F.3d at 1358-59. Case law instructs that where two causes combine to

cause a vaccine-related illness, and it is not possible to determine which of the causes was most

responsible, it is appropriate to find in favor of compensation. Shyface, 165 F.3d at 1352-1353

(finding in favor of petitioners where both a vaccine and an Escherichia coli infection

contributed to the death because concurrent forces may bring about a single harm.); Zamora v.

36

Sec’y of Health and Hum. Servs., No. 19-1718V, 2023 WL 6180857 (Fed. Cl. Spec. Mstr. Aug.

28, 2023).

In petitioner’s case, Dr. Callaghan opined that petitioner “had an upper respiratory tract

infection eight days before GBS, which he said is a reasonable timeframe” and, based on this,

concluded that petitioner’s GBS was post-infectious. Tr. at 322. He based his opinion that

petitioner had a URI on reports of a cough or run00ny nose which the record indicated began

about four days before the onset of GBS. However, an upper respiratory infection was not

observed or treated by medical personnel. He testified that URIs are “almost always diagnosed

purely on clinical history.” Id. at 323. According to Dr. Callaghan, petitioner had “some of the

most common symptoms of an upper respiratory tract infection,” and he argued that “was the

judgment of her medical providers.” Id. The medical records which mentioned symptoms such as

cough or congestion appeared to be based on answers to questions about recent history and not to

findings on physical examination. It did not appear that any physician actually diagnosed an

upper respiratory infection after performing multiple physical examinations that included the

respiratory system, albeit a URI was mentioned as part of her history. Dr. Callaghan pointed to

one note by Dr. Michael Weston, M.D. who did a neurology consult on the afternoon of July 23.

Dr. Weston in his plan indicated that Ms. Diponziano likely has GBS based on diffuse symmetric

weakness and a lack of reflexes. He said, “likely precipitated by recent URI.” Pet’r Ex 3 at 114.

A review of the history that he took indicated the onset of numbness and tingling in her fingers

followed by her toes during the evening of July 22. She had difficulty sleeping and woke up in

the middle of the night and again at 5 AM when she could not walk. He noted that she had

received the pneumovax on the 19th which was in error as she received it on July 11. “She

reported a slight confluent red rash on her left arm after the injection that has since resolved. She

reports on Tuesday (which was the 19th and four days before onset) she began to have a URI. She

has had a dry cough, rhinorrhea, and post nasal drip. She denies any abdominal pain.” Id at 80,

108. There was no indication that Dr. Weston conducted any examination of her respiratory tract

and was understandably focused on her loss of strength and reflexes.

The history from Cooper University Hospital fairly uniformly listed a cough as having

occurred about four days prior or as beginning on Tuesday which was four days before the onset

of GBS on Friday, July 22, 2016 or at least in the range of three to five days prior. Physical

exams performed by other providers found no evidence of a URI. On the day of admission at

8:49 AM, the examiner recorded oropharynx is clear and moist and mucous membranes are

normal. No oropharyngeal exudate, posterior oropharyngeal erythema or tonsillar abscesses.

Pulmonary and chest: Effort normal and breath sounds normal. No respiratory distress. She has

no wheezes. She has no rales. She exhibits no tenderness. Id. at 57.

A critical care note from later that day noted that petitioner had multiple allergies and

she states that she took a pneumonia vaccine around 10 days back which was followed by an

erythematous rash in her R arm/shoulder region. She has also had URI symptoms for the past 5

days. The rash was noted to be 4 x 4 cm. The ENT exam was normal, and her pulmonary exam

was clear to auscultation bilaterally, no rales or wheezes. Id. at 44. Treating physicians did not

find any evidence supportive of an active viral infection in petitioner’s chest x-ray, blood work,

or physical examination.

37

Petitioner’s medical history verified that she did have a history of seasonal allergies

which was confirmed by her husband’s testimony. The symptoms described of a cough with

postnasal drip is certainly consistent with allergy symptoms which Dr. Knobler testified would

be more likely to occur in the summer. She had not sought any treatment and remained active

through the week preceding her hospitalization including taking a trip to Atlantic City with her

sister.

In terms of possible causes of GBS most entries in the hospital chart listed “PPV

vaccine/uri” or just “vaccine/uri.”See, e.g., Pet’r Ex. 3 at 58 (“Guillain Barre-concern for given

bilateral weakness and recent uri/vaccine.”). Dr. Peterson wrote at 5:38 PM July 23, “79 year old

female Jehovah’s witness with [history of] hypothyroidism, multiple allergies presents with

rapidly progressive ascending paresis and dysesthesias. Concerning for GBS due to symmetrical

involvement. Possible triggers include pneumonia vaccine, preceding URI.” Id at 75. Dr.

Peterson also wrote, “The patient had a PNA vaccine (left deltoid) with rash-non-spreading.

Over the last 3-4 days she has had hoarseness. Denies dyspnea.” Id. at 76 Her chest x-ray showed

no infiltrate. Id. Patient received IVIG x 5 for GBS secondary to vaccine vs. uri. Id. at 78.

Another note by critical care physician Haney Mallemat, M.D. on July 25 noted concern for GBS

possibly triggered by recent PNA vaccine/URI. No respiratory distress currently, afebrile no

leukocytosis. Id. at 101, 129. Similar notes appeared at multiple other pages of the Cooper

University Hospital record indicating GBS possibly triggered by PNA vaccine/uri. Id. at 134,

140, 146, 158, 169 and 176.

While it is difficult to discern the level of thought process in attributing either or both of

these as the possible cause of her GBS, it did appear that most of the physicians at Cooper did

consider both the Prevnar vaccine and a possible URI as possible causes of the petitioner’s GBS.

In fact, it appeared that the history of the vaccination and the URI quickly elevated GBS to the

top of the differential diagnosis shortly after admission.

Dr. Knobler and Dr. Lee opined that there was no convincing evidence of an upper

respiratory infection and that in a person who suffered from allergies as does petitioner, it is

more likely that she may have had allergic rhinitis that would have explained her symptoms.

They noted that she had no treatment for a URI and did not have a fever. The ENT and

pulmonary exams as well as the chest x-ray in the hospital were normal. The lay witnesses at the

hearing indicated that petitioner had been active all week, including going on a trip to Atlantic

City with her sister indicating that at most she had minimal symptoms.

Dr. Callaghan cited to an article by Grief, 21 which found that “nasal congestion is seen in

80 to 100 percent of patients with URI, cough in 40 percent, fatigue and malaise in 20 to 25

percent, and fever in only 21 percent.” Tr. 330. He used this data to dispute Dr. Knobler’s

opinion that petitioner’s lack of fever supported the fact that she did not have a URI, noting that

“only one in a thousand people with URIs have fever.” Id. This testimony was given despite his

reference indicating that 21% of people with URI have fevers. He also disputed Dr. Knobler and

Dr. Lee’s opinions that the lack of treatment for URI supports the fact that petitioner did not have

one, explaining that treatment of a URI with antibiotics is “the exception, not the rule.” Id. He

21

Samuel Grief, Upper Respiratory Infections, 40 Primary Care Clinical Office Practice 757 (2013).

38

indicated that more than 90 to 95 percent “of URIs are treated symptomatically with mostly time

but also…treatments…to help you with your cough or your runny nose.” Id. Dr. Callaghan

opined that petitioner’s symptoms were not consistent with allergic rhinitis because malaise and

fatigue are atypical for allergies, and cough is less commonly associated with allergies. Id. at

336. Thus, Dr. Callaghan concluded that “petitioner clearly has the constellation of symptoms”

for a URI and that “her providers correctly diagnosed with a URI.” Id. at 330. He further noted

that this is particularly relevant “because we have really strong epidemiologic data linking URIs

with GBS.” Id. at 330.

Dr. Callaghan presented two articles, one by Greene 22 and another by Galeotti, 23 to

support the contention that “a causal association between an upper respiratory infection and GBS

is more common than the association between vaccines and GBS.” Id. at 338; Resp’t Ex. A-3;

Resp’t Ex. A-4. The two articles found that “the odds of developing GBS after upper respiratory

tract infection were much higher than after the flu…vaccine.” Id. at 338. These studies did find a

significantly higher number of GBS cases associated with gastrointestinal and respiratory

illnesses but as in Galeotti there was still a relative risk of 2.1 associated with the studied

influenza vaccine. In another article, filed by respondent, by van den Berg et al, 24 referring to the

influenza vaccine from 2009 the authors said, “but extensive national and international studies

found that vaccination was associated with only a small attributable risk of GBS. 1.6 excess

cases of GBS per 1,000,000 vaccine recipients, a frequency similar to that for all seasonal

vaccines. Resp’t Ex. D-1 at 4. Notably, however, “the fact that epidemiological evidence point[s]

to a virus rather than [the vaccine] as a trigger for the [injury] is insufficient to preclude

recovery.” Andreu, 569 F.3d at 1378 (citing Knudsen, 35 F.3d at 550).

Thus, although it can be fairly concluded that infections medically documented before the

onset of GBS are more common causes of GBS, none of the articles either assert that the

infections are the sole cause or that they explain all cases of GBS. Galeotti and van den Berg

both identified some excess relative risk secondary to vaccines. All of the articles consider

vaccination as a possible cause of GBS even as the risk is less than for example from the flu

itself.

Significantly, Dr. He agreed that the Prevnar vaccine administered 11 days prior to onset

and a possible URI occurring three to four days prior would both have been generating an

immune response at the time of onset and that it was possible that the combination of the two

acting at the same time could have caused a sufficiently overwhelming response to cause

autoimmunity. Tr. 312-13; See Shyface, 165 F3d at 1353. Special Master Millman, in Mulvaney,

noted, “the Federal Circuit emphasized that the vaccine does not have to be the predominant

22

Sharon Greene et al., Guillain-Barre Syndrome, Influenza Vaccination, and Antecedent Respiratory and

Gastrointestinal Infections: A Case-Centered Analysis in the Vaccine Safety Datalink, 2009-2011, PLoS ONE, June

2013.

23

Francesca Galeotti et al., Risk of Guillain Barre syndrome after 2010-2011 influenza vaccination, 28 Pharmaco-

Epidemiology 433 (2013).

24

Van den Berg et al., Guillain-Barre syndrome: pathogenesis, diagnosis, treatment and prognosis, 10 Nature

Reviews, Neurology 469 (2014).

39

factor in order for petitioner to prevail.” Shyface instructs that proof of a substantial factor

satisfies the requirements of the Vaccine Act. Id. at 1353.

At the outset, it is important to note that the evidence that petitioner actually had a URI is

scant. No physicians noted any signs of an active infection in petitioner’s blood work, on

physical examination, or in her chest x-ray. The only indication that petitioner may have had a

URI is based on her reported symptoms of a cough and congestion in the days prior to her

hospitalization. The mild upper respiratory symptoms described in the hospital record as being

reported could readily have been caused by allergic rhinitis particularly in a patient with an

allergy history and occurring in the summer months when an allergy attack would be more likely

than a respiratory infection. The physical examinations performed by various physicians in the

hospital did not find any indication of a respiratory infection and in fact documented a clear

respiratory tract. They did note that the petitioner said that she had a cough or hoarseness for

several days. All but one of the treating physicians in the hospital listed both the Prevnar vaccine

and the URI as possible triggers of the GBS. As Dr. Callaghan indicates that URIs are often

rather loosely diagnosed based on history alone, it would appear that the reference to a URI may

also be rather loosely made in that the types of symptoms reported by Ms. DiPonziano could just

as easily be caused by allergies. Furthermore, there were multiple examinations made of her

respiratory tract which found no evidence of a URI upon admission to the hospital.

Although a recent URI was mentioned in the records at multiple locations based on a history

of a cough and congestion, the evidence on causation is, at most, in equipoise. These symptoms

could readily have been explained by allergies as testified by Dr. Knobler. Additionally,

respondent’s expert, Dr. He agreed that, in the event there was a mild URI in the interval between

the vaccine and the onset of GBS, the vaccine and an infection, acting in concert, could have

caused the overwhelming immune response leading to autoimmunity. Although the possible

occurrence of a mild upper respiratory infection prior to the onset of the petitioner’s GBS cannot

be disregarded, neither can the possible allergic rhinitis explanation or the fact of the two acting

in concert to cause GBS.

When there are two potential causes for an illness, a petitioner is not required to eliminate

the other potential cause in order to be entitled to compensation. Walther v. Sec’y of Health &

Hum. Servs., 485 F.3d 1146, 1150 (Fed. Cir. 2007) (ruling that “Petitioner does not bear the

burden of eliminating alternative independent potential causes.”). Moreover, in order for the

government to meet its burden, it must provide preponderant evidence that a particular agent or

condition unrelated to the vaccine was the “sole substantial factor in bringing about the injury.”

de Bazan, 539 F.3d at 1354. Given my conclusion that the evidence of the URI as an alternative

cause is at best, in equipoise, the government has failed in its burden of persuasion to

demonstrate an alternative cause by a preponderance of the evidence. Knudsen, 35 F.3d at 551

(“If the evidence [on alternative cause] is seen in equipoise, then the government has failed in its

burden of persuasion and compensation must be awarded.”). Accordingly, the petitioner is

entitled to compensation.

40

VI. Conclusion

After a review of the entire record and for the foregoing reasons, I find that petitioner has

established by preponderant evidence that the Prevnar 13 vaccine she received more likely than

not caused her Guillain-Barre syndrome. Thus, petitioner is entitled to compensation. A separate

damages order will be issued.

IT IS SO ORDERED.

s/ Thomas L. Gowen

Thomas L. Gowen

Special Master

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