Sprenger v. Secretary of Health and Human Services

In the United States Court of Federal Claims

OFFICE OF SPECIAL MASTERS

Filed: November 14, 2023

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

JEFFREY W. SPRENGER, * PUBLISHED

*

Petitioner, * No. 18-279V

*

v. * Special Master Nora Beth Dorsey

*

SECRETARY OF HEALTH * Ruling on Entitlement; Pneumococcal

AND HUMAN SERVICES, * Conjugate (“Prevnar 13”) Vaccine;

* Guillain-Barré Syndrome (“GBS”).

Respondent. *

*

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

Cary Michael Toland, Herrman and Herrman, PLLC, Brownsville, Texas, for Petitioner.

Ryan Daniel Pyles, U.S. Department of Justice, Washington, DC, for Respondent.

RULING ON ENTITLEMENT1

On February 22, 2018, Jeffrey W. Sprenger (“Petitioner”) filed a petition for

compensation under the National Vaccine Injury Compensation Program (“Vaccine Act” or “the

Program”), 42 U.S.C. § 300aa-10 et seq. (2018),2 alleging that he suffered Guillain-Barré

Syndrome (“GBS”) as the result of an influenza (“flu”) vaccination he received on October 9,

1

Because this Ruling contains a reasoned explanation for the action in this case, the undersigned

is required to post it on the United States Court of Federal Claims’ website and/or at

https://www.govinfo.gov/app/collection/uscourts/national/cofc in accordance with the E-

Government Act of 2002. 44 U.S.C. § 3501 note (2018) (Federal Management and Promotion of

Electronic Government Services). This means the Ruling will be available to anyone with

access to the Internet. In accordance with Vaccine Rule 18(b), Petitioner has 14 days to

identify and move to redact medical or other information, the disclosure of which would

constitute an unwarranted invasion of privacy. If, upon review, the undersigned agrees that the

identified material fits within this definition, the undersigned will redact such material from

public access.

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 (2018) (“Vaccine Act” or “the Act”). All citations in this Ruling to

individual sections of the Vaccine Act are to 42 U.S.C.A. § 300aa.

2016 and a pneumococcal conjugate (“Prevnar 13”) vaccination he received on April 12, 2017.3

Petition at Preamble, ¶¶ 2, 16 (ECF No. 1). Respondent argued against compensation, stating

“this case is not appropriate for compensation under the terms of the Act.” Respondent’s Report

(“Resp. Rept.”) at 1 (ECF No. 26).

After carefully analyzing and weighing the evidence presented in accordance with the

applicable legal standards, the undersigned finds Petitioner has provided preponderant evidence

that the Prevnar 13 vaccine he received caused his GBS, satisfying his burden of proof under

Althen v. Secretary of Health & Human Services, 418 F.3d 1274, 1280 (Fed. Cir. 2005).

Accordingly, Petitioner is entitled to compensation.

I. ISSUES TO BE DECIDED

Diagnosis is at not in issue. “[R]espondent does not dispute [P]etitioner’s diagnosis of

GBS.” Resp. Brief on Entitlement (“Resp. Br.”), filed Apr. 4, 2023, at 13. (ECF No. 99).

The parties dispute causation. Petitioner contends he has provided preponderant evidence

that the Prevnar 13 vaccination caused his GBS, and that this evidence meets the Althen criteria.

Petitioner’s (“Pet.”) Br., filed Mar. 21, 2013, at 1, 10 (ECF No. 96). Respondent disagrees and

argues Petitioner (1) failed to present a reliable medical theory causally connecting vaccination

and GBS, (2) failed to show a logical sequence of cause and effect between vaccination and his

GBS, and (3) failed to show a proximate temporal relationship between Petitioner’s vaccinations

and his GBS. Resp. Br. at 13-26.

II. BACKGROUND

A. Procedural History

Petitioner filed her petition on February 22, 2018, and filed medical records in the

following months.4 Petition; Pet. Exhibits (“Ex.”) 1-34. Respondent filed his Rule 4(c) Report

arguing against compensation on June 12, 2019. Resp. Rept. at 1.

On November 6, 2019, Petitioner filed an expert report from Dr. Gary Pekoe. Pet. Ex.

37. On February 10, 2020, Respondent filed an expert report from Dr. You-Wen He. Resp. Ex.

A. Petitioner filed supplemental expert reports from Dr. Pekoe on April 9, 2020 and January 11,

3

Petitioner also alleges that a shingles vaccine, Zostavax, administered on April 12, 2017, is

causally related to his GBS. Petition at Preamble, ¶¶ 2, 16. However, Zostavax is not a vaccine

covered under the Vaccine Injury Table. See, e.g., Scanlon v. Sec’y of Health & Hum. Servs.,

114. Fed. Cl. 135, 142 (2013); 42 C.F.R § 100.3(a). Additionally, Petitioner no longer seeks

compensation based on receipt of the flu vaccination he received in October 2016, and his claim

is based solely on the Prevnar 13 vaccination he received on April 12, 2017. See Petitioner’s

Brief on Entitlement (“Pet. Br.”), filed Mar. 21, 2023 (ECF No. 96).

4

Petitioner continued to file medical records throughout the course of litigation.

2

2021. Pet. Exs. 39, 46. On April 5, 2021, Respondent filed a responsive report from Dr. He, and

Petitioner filed a supplemental report from Dr. Pekoe on June 11, 2021. Resp. Ex. D; Pet. Ex.

42.

On February 4, 2022, the case was reassigned to the undersigned. Notice of

Reassignment dated Feb. 4, 2022 (ECF No. 52). A status conference was held on February 24,

2022 during which the undersigned gave her preliminary opinions on the case. Order dated Feb.

24, 2022 (ECF No. 53). The undersigned preliminarily found the basis for Dr. Pekoe’s opinions

unpersuasive. Id. at 2. While the undersigned noted the case was not fully developed at that

time, the parties agreed to resolve the matter through a ruling on the record after additional

expert reports were filed. Id. at 3.

Petitioner filed an expert report by Dr. Lawrence Steinman on June 28, 2022. Pet. Ex.

57. On October 13, 2022, Respondent filed expert reports by Dr. He and Dr. Dara Jamieson.

Resp. Exs. E, U.

On November 18, 2022, Petitioner filed a status report indicating he did not wish to file

additional expert reports and that the case was ready for submission on the issue of entitlement.

Pet. Status Rept., filed Nov. 18, 2022 (ECF No. 88). Respondent filed a joint status report on

December 19, 2022 with an agreed upon briefing schedule and indicated he was investigating the

feasibility of a potential settlement. Resp. Joint Status Rept., filed Dec. 19, 2022 (ECF No. 90).

However, on January 20, 2023, Respondent advised he declined to entertain settlement

negotiations at that time and reiterated the proposed briefing schedule—simultaneous briefs on

the merits, followed by permissive replies. Resp. Joint Status Rept., filed Jan. 20, 2023 (ECF

No. 94).

On March 21, 2023, Petitioner filed his brief for a ruling on the record on entitlement.

Pet. Br. Respondent filed his brief on April 4, 2023. Resp. Br. On April 18, 2023, Petitioner

filed a reply. Pet. Reply to Resp. Br. (“Pet. Reply”), filed Apr. 18, 2023 (ECF No. 100).

This matter is now ripe for adjudication.

B. Medical Terminology

GBS is an illness that causes “acute flaccid paralysis, characterized by symmetrical

weakness of the limbs, and hyporeflexia or areflexia, which reaches a maximum severity within

[four] weeks []. Sensory symptoms, such as [] numbness, usually start distally and have a

symmetrical pattern.” Resp. Ex. A, Tab 1 at 1.5 A common subtype of GBS is “acute

inflammatory demyelinating polyneuropathy (AIDP).” Id. The condition is relatively rare, with

a reported incidence of 0.89-1.89 cases per 100,000 person-years in Western countries, affecting

5

Bianca van den Berg, Guillain-Barré Syndrome: Pathogenesis, Diagnosis, Treatment and

Prognosis, 10 Nature Revs. Neurology 469 (2014).

3

all ages, with an increased risk in older adults. Resp. Ex. R at 1.6 Most patients have symptoms

that progress for one to three weeks after initial symptoms begin. Id. at 3. The majority are

“unable to walk independently when maximum weakness is reached.” Id. Respiratory difficulty

and other complications may occur. Id. Patients may have a severe clinical course, and 20% are

unable to walk for up to six months after onset. Id. Weakness is the prominent manifestation.

Id. Other symptoms may include sensory disturbances, cranial nerve palsies, and dysautonomia.7

Id. at 9.

GBS is thought to be an autoimmune disease. Pet. Ex. 67 at 1.8 “[T]he immune system

starts to destroy the myelin sheath that surrounds the axons of [] peripheral nerves.” Id. The

axons of nerves may also be affected. Id. Once the myelin sheath or axons of the peripheral

nerves are injured, the nerves are unable to send signals in the usual fashion. Id. “[M]uscle

weakness and tingling sensations” occur in the “hands and feet and progress upwards.” Id. GBS

may be triggered by infections or immunizations. Id.; see also Resp. Ex. Z at 1 (“[A]proximately

two-thirds of all cases are preceded by a gastrointestinal or respiratory infection within the prior

[three] months.”).9

The underlying etiology of GBS “is considered to be an immune-mediated disorder

resulting from generation of autoimmune antibodies and/or inflammatory cells which cross-react

with epitopes on peripheral nerves and roots, leading to demyelination or axonal damage or

both.” Resp. Ex. CC at 2.10 In an article filed by Respondent, the way infection and vaccines

may cause GBS is described below:

6

Nobuhiro Yuki & Hans-Peter Hartung, Guillain-Barré Syndrome, 366 New Eng. J. Med. 2294

(2012).

7

Dysautonomia is a “malfunction of the autonomic nervous system.” Dysautonomia, Dorland’s

Med. Dictionary Online, https://www.dorlandsonline.com/dorland/definition?id=15146 (last

visited Oct. 26, 2023). Autonomic nervous system is “the portion of the nervous system

concerned with regulation of the activity of cardiac muscle, smooth muscle, and glandular

epithelium; usually restricted to the two visceral efferent peripheral components, the sympathetic

nervous system, and the parasympathetic nervous system.” Autonomic Nervous System,

Dorland’s Med. Dictionary Online, https://www.dorlandsonline.com/dorland/definition?

id=111779 (last visited Oct. 26, 2023).

8

Nat’l Inst. Neurological Disorders & Stroke, Guillain-Barré Syndrome Fact Sheet

https://www.ninds.nih.gov/guillain-barre-syndrome-fact-sheet (last updated Aug. 26, 2014).

9

Roger Baxter et al., Lack of Association of Guillain-Barré Syndrome with Vaccinations, 57

Clinical Infectious Diseases 197 (2013).

10

James J. Sejvar et al., Guillain-Barré Syndrome and Fisher Syndrome: Case Definitions and

Guidelines for Collection, Analysis, and Presentation of Immunization Safety Data, 29 Vaccine

599 (2011).

4

The concept of “molecular mimicry” involves a situation in which

epitopes of a pathogen or vaccine protein could initiate development of antibodies

and/or T-cells that could cross-react with epitopes on peripheral nerve myelin or

axonal glycoproteins or ganglioside moieties. Activated macrophages could

potentially be targeted to antigens on the myelin sheath and subsequently invade

the basement membrane resulting in demyelination or, alternatively, invade at the

nodes of Ranvier[11] to result in axonal damage.

Id. at 3.

C. Summary of Medical Records12

Prior to vaccination, Petitioner’s medical history included fatigue, a well-controlled

seizure disorder, and diabetes mellitus type II (metformin prescribed for diabetes in August

2016). Pet. Ex. 29 at 71-74, 87; Pet. Ex. 33 at 36-38, 47, 50-52. On October 9, 2016, at 59 years

old, Petitioner received a flu vaccination. Pet. Ex. 3 at 1.

On November 21, 2016, Petitioner was seen in primary care for bloodwork and did not

have any concerns or complaints at that time. Pet. Ex. 29 at 90. He had “equal [and] present”

sensation in his lower extremities. Id. On November 29, 2016, Petitioner was seen in primary

care for a cough for the previous five days, lack of energy, chest congestion, and headache. Id.

at 91. The assessment was bronchitis. Id. On December 30, 2016, Petitioner returned for the

same symptoms, with a month’s duration. Id. Petitioner reported that he had improved for two

weeks, but then developed an enlarged prostate for which he was receiving care from a urologist

and was on Bactrim and Flomax. Id. The assessment again was bronchitis. Id. at 92.

On January 3, 2017, Petitioner presented to Memorial Hermann Hospital for a one-day

history of a rash after recently starting a steroid dose pack and Bactrim to “treat his prostate.”

Pet. Ex. 30 at 12, 45. Petitioner’s musculoskeletal sensation was intact, and he had no weakness

on a review of systems. Id. at 20, 45. The assessment was a likely allergic reaction to Bactrim,

and the plan was to switch Bactrim to Cipro if Petitioner’s urologist concurred. Id. at 48. In a

11

The nodes of Ranvier are “constrictions occurring on myelinated nerve fibers at regular

intervals of about 1 mm; at these sites the myelin sheath is absent and the axon is enclosed only

by Schwann cell processes.” Nodes of Ranvier, Dorland’s Med. Dictionary Online,

https://www.dorlandsonline.com/dorland/definition?id=93095 (last visited Oct. 26, 2023).

Schwann cells are “any of the large nucleated cells whose cell membrane spirally enwraps the

axons of myelinated peripheral neurons and is the source of myelin; a single Schwann cell

supplies the myelin sheath between two nodes of Ranvier.” Schwann Cell, Dorland’s Med.

Dictionary Online, https://www.dorlandsonline.com/dorland/definition?id=64407 (last visited

Oct. 26, 2023).

12

This summary of medical records is quoted verbatim from Respondent’s Brief, as the

undersigned finds it to be an accurate representation of the records. Resp. Br. at 3-7.

5

follow-up with primary care on January 4, 2017 for “hives all over body [for] three days,”

Petitioner was prescribed the antihistamine, Atarax. Pet. Ex. 29 at 92.

On February 27, 2017, Petitioner was seen in primary care for a cough, nasal congestion,

body aching, and headache for the previous three days. Pet. Ex. 29 at 92.13 The assessment was

an upper respiratory infection, and Petitioner was prescribed a Z-Pak, Flonase, an Albuterol

inhaler, and Robitussin. Id. at 93. A flu test was noted to be negative. Id. On March 2, 2017,

Petitioner called his primary provider’s office to refill Robitussin. Id. On March 22, 2017, the

primary care office prescribed Petitioner fluticasone, a nasal steroid. Id.

Petitioner received the Prevnar 13 vaccine and a shingles vaccine (Zostavax) on April 12,

2017. Pet. Ex. 4 at 1.

On April 27, 2017, Petitioner saw his primary care provider for numbness in his hands,

feet, and lips. Pet. Ex. 29 at 93. Petitioner’s numbness was of a two-day duration. Id. at 88. He

also reported neck pain of a four-day duration. Id.

Petitioner presented to Memorial Hermann Hospital on April 29, 2017 for a four- to five-

day history of “numbness/tingling to [his] bilateral feet and ankles, hands and wrists.” Pet. Ex.

30 at 123. The symptoms seemed to wax and wane but were progressively worsening. Id. He

also reported bilateral face numbness. Id. He felt like he was “‘tasting salt’ all the time.” Id. In

a hospital-based neurology consultation with Dr. Atta Rehman, Petitioner reported being

diagnosed with diabetes about six months prior. Id. at 86. Petitioner continued that he “started

having numbness and tingling in his feet Tuesday [April 25] when he was vacationing in Las

Vegas that according to him traveled up to his legs and he noticed some numbness in his hands

as well.” Id. The history continued that on the next day (April 26), he felt an “off-balance

feeling” and “left-sided low back pain.” Id. In the hospital, Petitioner was prescribed

gabapentin, and he was discharged on May 1, 2017. Id. at 95, 143. A lumbar puncture had not

showed evidence of GBS. Id. at 96. The discharge diagnoses were “[p]aresthesia likely

secondary to diabetic neuropathy [versus GBS],” sciatica, accelerated hypertension, diabetes,

hyperlipidemia, a seizure disorder, and gastroesophageal reflux. Id.

On May 2, 2017, Petitioner saw his primary care provider with a complaint of “getting

weaker, cannot walk,” and he was referred to a neurologist. Pet. Ex. 29 at 89. That same day,

Petitioner saw neurologist Dr. Jose Diaz. Pet. Ex. 33 at 54. The assessment was GBS, and

Petitioner was to be admitted for plasmapheresis. Id. Petitioner was readmitted to Memorial

Hermann Hospital from May 2-9, 2017. Pet. Ex. 30 at 430, 545-46. The discharge diagnoses

included GBS, and Petitioner was discharged to inpatient rehabilitation. Id. at 430, 1382.

Petitioner was in inpatient rehabilitation until May 24, 2017. Pet. Ex. 42 at 6-12.

In follow-up with Dr. Diaz on July 12, 2017, Petitioner was “doing much better after

plasmapheresis and rehab” and “continu[ed] to improve with physical therapy.” Pet. Ex. 33 at

58. Petitioner specifically reported facial and throat numbness. Id. On examination, strength

13

The record is cut off, but it appears that Petitioner had been exposed to sick contacts (“+ sick .

. . work”). Pet. Ex. 29 at 92-93.

6

was 4/5 in all four extremities; Petitioner had no deep tendon reflexes; and he had decreased

sensation in his distal legs and feet. Id. Petitioner reported April 25, 2017 as the onset of his

symptoms associated with GBS. Id. Dr. Diaz noted, “[b]ased on the timing and sequence of

events, [Petitioner’s] GBS is most likely secondary to the vaccinations received on April 12,

2017.” Id. Petitioner was to continue on gabapentin. Id.

On January 10, 2018, Dr. Diaz reported that Petitioner’s “extremity strength [had]

significantly improved,” and Petitioner had no breathing or swallowing difficulty. Pet. Ex. 33 at

80. However, he “remain[ed] with some discomfort[,] including discomfort over his face and

around his eyes.” Id. On examination, Petitioner’s strength was 5/5; his deep tendon reflexes

were 2+ and “symmetric with cross adductors;” Petitioner’s sensory examination was “intact;”

and he had a normal gait. Id. The assessment was GBS with continued, slow improvement and

hyperreflexia. Id. at 81. Dr. Diaz noted that Petitioner had been completely areflexic, and

accordingly, hyperreflexia was “concerning for the possibility of a central pathology including

the possibility of disseminated encephalomyelitis.” Id. Accordingly, he ordered cervical and

brain MRIs. Id. A January 29, 2018 cervical-spine MRI showed cervical spondylosis, but no

enhancements to indicate, for example, encephalomyelitis. Id. at 100. A brain MRI on the same

date was unremarkable. Id. at 102.

On May 11, 2018, the “Department of Assistive and Rehabilitative Services” sent

Petitioner to occupational medicine specialist Dr. Faiyaz Bhojani. Pet. Ex. 33 at 215-18.

Petitioner complained of continued tightness and numbness in his feet, hands, and around his

nose and eye areas. Id. at 215. He also complained of “severe fatigue,” a lack of sleep, poor

balance, and a feeling of jerking movement. Id. Dr. Bhojani concluded in part that

[i]n regards to the ability to perform work-related functions of [a] physical nature,

[Petitioner] is able to sit for long periods of time, stand for short to moderate

periods of time and walk short to moderate distances and lift light to moderate

weights. [Petitioner’s] fine finger control is within normal limits and [he] is able

to hear, speak, and have conversation which is fluent and understandable.

[Petitioner’s] gait is broad with a slight right limp and he can do toe and heel

walking for a few steps, as well as tandem walking but no squatting. His grip

strength is good and he can reach, finger and handle [sic] but his feeling sensation

is decreased. . . . There is no reproducible fatigue on motor examination during

examination.

Id. at 218.

On July 12, 2018, in follow-up with Dr. Diaz, Petitioner complained of tingling in his

hands, feet, and nose. Pet. Ex. 33 at 125. His feet felt heavy; he complained of fatigue; and he

felt he had balance issues when standing and starting walking. Id. The bottom of his feet felt

sore if he stood in place for very long. Id. He had hand tremors since his last visit in January.

Id. Petitioner reported short-term memory issues and difficulty getting words out at times. Id.

Dr. Diaz did not feel petitioner was worsening, or that IVIG was warranted. Id. at 126.

7

As of December 6, 2022, as noted during a follow-up visit with Dr. Diaz, Petitioner

reported numbness in his feet, left lower leg, hands, and in his nose area that was unchanged

since his prior visit in April 2022. Pet. Ex. 93 at 1. He reported a “slight tremor” in his hands

“at times.” Id. The assessment included that Petitioner had a “significant residual component”

with regard to GBS symptomatology—that he had improved, but never returned to baseline. Id.

at 3. He was on gabapentin (600 mg, three times daily) for “neuropathic discomfort.” Id. (also

noting that gabapentin “significantly helped his pain and discomfort”).

No other relevant medical records were filed.

D. Affidavits

On December 1, 2017, Petitioner executed an affidavit. Pet. Ex. 28 at 6. Petitioner

recalled that on October 9, 2016, he received a flu vaccine and thereafter, “began to feel

weakness, fatigue, coughing and chest congestion[,] and some numbness in [his] extremities.”

Id. at ¶ 1. He felt like he had the flu but a flu test was negative. Id. He averred he “felt the same

symptoms through 2017.” Id.

In preparation for travel to visit his sister, Petitioner received the Prevnar 13 vaccine and

a shingles vaccine on April 12, 2017. Pet. Ex. 28 at ¶ 2. Toward the end of his week-long visit,

he “began noticing an increase in the symptoms that had been with [him] since November: a

severe tingling in [his] hands and feet as though they were asleep, and [he] experienced

difficultly with walking and balancing.” Id. at ¶ 3. On April 27, Petitioner noted he “felt an

increase of the numbness and tingling up [his] arms, hands, nose, lips[,] and legs, and [his]

balance issues were becoming more severe. Later in the day, [he] began to experience sharp

pains up [his] legs and was unable to get comfortable, and [he] was severely fatigued.” Id. He

recalled the numbness, tingling, and pain continued to worsen the next day and on April 29, he

“was weak and could not walk without assistance.” Id.

Petitioner described his hospital course from admission on April 29, 2017 to discharge on

May 1, 2017, including the spinal tap that was negative for elevated proteins. Pet. Ex. 28 at ¶¶ 4-

5. During the evening after his discharge, Petitioner could not stand or walk. Id. at ¶ 5. His

neurologist, Dr. Diaz saw him on May 2, assessed him with GBS, and was sent to the emergency

room. Id. at ¶ 6. After being admitted to the hospital again on May 2, 2017, Petitioner received

plasmapheresis infusions, had a spinal tap that was positive for elevated proteins, and was

diagnoses with GBS. Id. at ¶ 7. Petitioner recalled that “[d]uring this time, [his] weakness,

paralysis, numbness[,] and pain dramatically increased.” Id. He “continued deteriorating until

approximately May 9[] when [he] appeared to have reached a plateau.” Id.

Lastly, Petitioner recounted that on May 9, 2017, he was transferred to inpatient

rehabilitation, and on May 24, he transitioned to outpatient rehabilitation. Pet. Ex. 28 at ¶¶ 8-9.

8

E. Expert Reports14

1. Petitioner’s Expert, Dr. Lawrence Steinman15

a. Background and Qualifications

Dr. Steinman is board certified in neurology and has practiced neurology at Stanford

University for over 40 years. Pet. Ex. 57 at 1; Pet. Ex. 58 at 1-2. He received his B.A. from

Dartmouth College in 1968 and his M.D. from Harvard University in 1973. Pet. Ex. 58 at 1.

Thereafter, he completed an internship in surgery, residency in pediatrics, and residency in

pediatric and adult neurology from Stanford University Hospital, as well as three fellowships,

including one in clinical immunology. Id. Dr. Steinman is currently a Professor at Stanford

University. Id. Dr. Steinman treats patients with GBS. Pet. Ex. 57 at 1. He has authored or co-

authored over 500 publications. Pet. Ex. 58 at 5-47. Dr. Steinman has authored papers on

molecular mimicry, as demonstrated by his CV. Id.; see also Pet. Ex. 57 at 1. One of Dr.

Steinman’s specialties is in the area of multiple sclerosis (“MS”), and he has received a Charcot

Prize for Lifetime Achievement due to his research in MS. Pet. Ex. 57 at 2. In 2015, he was

elected to the National Academy of Sciences. Id. Dr. Steinman is also a member in the National

Academy of Medicine. Id.

b. Opinion

i. Althen Prong One

Dr. Steinman opined that the Prevnar 13 vaccination can cause GBS. Pet. Ex. 57 at 32.

The focus of Dr. Steinman’s expert reports and opinions was how the Prevnar 13 vaccine can

trigger GBS via molecular mimicry. Id. at 11. He reviewed the components of the vaccine and

the main targets of the human immune response in GBS and proposed two mechanisms whereby

molecular mimicry can trigger GBS following Prevnar 13 vaccination. The first involves

homology between the components in the vaccine and phosphoglycerol components in the

myelin of peripheral nerves. Id. at 12-21. The second involves homology between CRM197 in

the vaccine and Contactin-1, a protein found in humans. Id. at 21-31.

14

Although the undersigned has reviewed all the expert reports, for the sake of brevity this

Ruling does not include every detail of the experts’ opinions. Instead, the undersigned focuses

on the experts’ material opinions, as they relate to the relevant issue of causation.

15

Petitioner filed one expert report from Dr. Steinman. Pet. Ex. 58. Petitioner also filed four

expert reports from Gary Pekoe, Ph.D. Immunopharmacologist. Pet. Exs. 37, 39, 42, 46.

Petitioner stated in his brief that “his claim relies on [Dr.] Steinman’s expert report and medical

theory that the Prevnar 13 vaccination on April 12, 2017[] caused his vaccine injury.” Pet. Br. at

10 n.1. “Accordingly, Petitioner will not be discussing nor submitting any theories put forth by

Petitioner’s initial expert, [Dr. Pekoe,] regarding vaccinations received outside of temporal

relevance to Petitioner’s GBS (i.e. the Flulaval Quad vaccine).” Id. Therefore, the undersigned

will not discuss Dr. Pekoe’s reports or opinions and will limit her discussion and analysis to the

Prevnar 13 vaccination and the theories offered by Dr. Steinman.

9

1. Phosphoglycerol16 in Serotypes 18C and 23F

The first mechanism described by Dr. Steinman involves homology between

phosphoglycerol in the Prevnar 13 vaccine, present in the antigens of Streptococcus pneumoniae

(“S. pneumoniae”) serotypes 18C and 23F, and phospholipids, specifically glycerophosphate and

glycerocholine in the human myelin sheath. Pet. Ex. 57 at 12-16; see also Pet. Ex. 69 at 24

(Prevnar 13 package insert).

Based upon information obtained from the vaccine patent,17 Dr. Steinman explained that

the glycerol phosphate side chains in the vaccine are necessary for its immunogenicity.18 Pet.

Ex. 57 at 14-15. Dr. Steinman cited an article by Chang et al.19 to support his opinion that the

phosphoglycerol component is preserved during the process of making the vaccine. Id. (citing

Pet. Ex. 72 at 1). Chang et al. wrote “it is shown that glycerol-phosphate must be preserved for

conserving adequate antigenicity of the 18C capsular polysaccharide.” Pet. Ex. 72 at 1.

Dr. Steinman explained how the data from the vaccine patent and the studies described

above relate to the pathogenesis of GBS. Pet. Ex. 57 at 12-13. He opined that phospholipids20

are the targets of antibodies in GBS. Id. He asserted that antibodies to phosphoglycerol

structures interact with myelin components triggering GBS. Id. at 13. Based on his own

research, Dr. Steinman explained that “phospholipids are components of the myelin sheath in

humans, and they are targeted by antibodies” leading to neuroinflammation in GBS. Id.

16

Phospho- is a “prefix[] indicating the presence of phosphorus in a compound.” Stedman’s

Medical Dictionary 1486 (28th ed. 2006). Glycerol is “[a] sweet viscous fluid obtained by the

saponification of fats and fixed oils; used as a solvent, as a skin emollient, . . . and as a vehicle

and sweetening agent.” Stedman’s at 820.

17

The patent is filed as Petitioner’s Exhibit 74. The description of the glycerol phosphate side

chain in 18C can be found at page 34, and a diagram of the chemical structure is at page 6.

18

Immunogenicity is defined as “the property that endows a substance with the capacity to

provoke an immune response, or the degree to which a substance possesses this property.”

Immunogenicity, Dorland’s Med. Dictionary Online, https://www.dorlandsonline.com/dorland/

definition?id=24893 (last visited Oct. 26, 2023).

19

Janoi Chang et al., Relevance of O-acetyl and Phosphoglycerol Groups for the Antigenicity of

the Streptococcus pneumoniae Serotype 18C Capsular Polysaccharide, 30 Vaccine 7090 (2012).

20

Phospholipid is defined as “any lipid that contains phosphorus, including those with a glycerol

backbone (phosphoglycerides and plasmalogens) . . . . Phospholipids are the major form of lipid

in all cell membranes.” Phospholipid, Dorland’s Med. Dictionary Online,

https://www.dorlandsonline.com/dorland/definition?id=38759 (last visited Nov. 1, 2023).

10

In support of this aspect of his opinion, Dr. Steinman relied on several articles. The first

was authored by Ho et al.21 and Dr. Steinman is also a named author. Pet. Ex. 65. The authors

showed that in the demyelinating disease MS, autoantibodies primarily target a phosphoglycerol

component of myelin. Pet. Ex. 57 at 13 (citing Pet. Ex. 65 at 1). The “findings indicate[d] that

myelin phospholipids are targeted by autoimmune responses in MS.” Pet. Ex. 65 at 9.

In Gilburd et al.,22 the authors “studied the reactivity of GBS sera with various

phospholipids which are known to be important constituents of myelin and serve as autoantigens

in other autoimmune conditions.” Pet. Ex. 70 at 2. Six of the 16 patients with GBS had

autoantibodies to various phospholipids. Id. at 2, 5. However, the authors suggested this was

“probably [] a result of [] myelin damage rather than [the] cause of demyelination.” Id. at 2, 6.

Nakos et al.,23 studied anti-phospholipid antibodies in nine patients with GBS. Pet. Ex.

71 at 1. All nine patients in the study had anti-phospholipid antibodies and no such antibodies

were detected in the nine control subjects. Id. The authors “detected a wide range of anti-

phospholipid antibodies in patients with idiopathic GBS,” and “[a]ll nine GBS patients

developed anti-phospholipid antibodies directed against at least one lipid during the course of the

disease.” Id. at 5. They wrote, “[t]he association of GBS and certain autoimmune diseases,

including systemic lupus erythematosus, is well recognized,” and they noted “[h]igh levels of

anti-phospholipid antibodies were expressed in a patient with lupus like syndrome who

developed secondary GBS.” Id. at 6. The authors explained that “[i]t is thought that whenever

polyneuropathy occurs in the context of autoimmune diseases, mainly in systemic lupus

erythematosus, where anti-phospholipid activity already exists, these antibodies can cross-react

with phospholipids and mediate damage in neural structures containing the particular

phospholipids.” Id. Of note, the GBS patients in the Nakos et al. study had primary GBS

(relevant here), not the secondary form like that which occurs in patients with lupus. Id. The

authors also observed anti-ganglioside antibodies, but only in 44% of the patients. Id. They

concluded,

[i]t is not well understood whether these anti-phospholipid antibodies play

a role in the pathogenesis of the polyneuropathy or represent a part of a more

extensive immunoreaction that takes place in the GBS. However,

immunopathology in autopsies suggests that antibody mediated injury is a

predominant disorder in the demyelinating form of GBS. The immune attack is

directed against components of Schwann cell membrane and is accompanied by

the characteristic feature of vesicular demyelination. Therefore, it is crucial to

21

Peggy P. Ho et al., Identification of Naturally Occurring Fatty Acids of the Myelin Sheath

That Resolve Neuroinflammation, 4 Sci. Translational Med. 1 (2012).

22

B. Gilburd et al., Autoantibodies to Phospholipids and Brain Extract in Patients with the

Guillain-Barré Syndrome: Cross-Reactive or Pathogenic?, 16 Autoimmunity 57 (1993).

23

G. Nakos et al., Anti-Phospholipid Antibodies in Serum from Patients with Guillain-Barré

Syndrome, 31 Intensive Care Med. 1401 (2005).

11

investigate how anti-phospholipid antibodies are related to specific antigens in

Schwann cell membrane.

....

Our findings suggest that in GBS there is a more extensive immune

reaction, beyond the well known antiganglioside production, which has been

related to the demyelination of the peripheral nerves.

Id. at 6-7.

Lastly, Dr. Steinman cited a study by Bryson et al.24 of antibodies directed to serotype

23F “from humans who were immunized with a pneumococcal vaccine (Pneumovax 23) that

contains 23F.”25 Pet. Ex. 57 at 17 (citing Pet. Ex. 75 at 2). He explained Bryson et al. showed

X-rays of “human antibody targeting the 23F component of S. pneumonia.” Id. (citing Pet. Ex.

75 at 2). Dr. Steinman opined the X-rays demonstrate the “human antibody response to 23F after

the human received a pneumococcal vaccine intended to elicit antibodies to 23F.” Id. at 18. Dr.

Steinman concluded that the “data from the Bryson [et al.] article demonstrate unequivocally that

the immune response to the serotype 23F component of Pneumovax 23 targets the

phosphoglycerol in serotype 23F.” Id. at 20 (emphasis omitted).

In summary, Dr. Steinman’s theory is based on molecular mimicry, and he averred that

antibodies to the phosphoglycerol structures present in the components of Prevnar 13 (via

serotypes 18C and 23F) target an immune response in phospholipids in the myelin components

of peripheral nerves, triggering GBS. Pet. Ex. 57 at 21.

2. CRM197 and Contactin-1

24

Steve Bryson et al., Structures of Preferred Human IgV Genes–Based Protective Antibodies

Identify How Conserved Residues Contact Diverse Antigens and Assign Source of Specificity to

CDR3 Loop Variation, 196 J. Immunology 4723 (2016).

25

Serotype 23F is included in both Prevnar 13 and Pneumovax 23. See Pet. Ex. 69 (Prevnar 13

package insert); Pet. Ex. 77 (Pneumovax 23 package insert).

12

The second homology posited by Dr. Steinman is between the protein carrier in the

vaccine, CRM197,26 and Contactin-1,27 a protein found in humans. Pet. Ex. 57 at 21. Prevnar 13

is a conjugate vaccine in which the individual polysaccharides of the capsular antigens of S.

pneumoniae are linked to a non-toxic diphtheria CRM197 protein. Id. at 12 (citing Pet. Ex. 69 at

24). “CRM197 is a nontoxic variant of diphtheria toxin,” used as a protein carrier which makes

the vaccine more immunogenic. Id. (quoting Pet. Ex. 69 at 24). CRM197 differs from diphtheria

toxin by only one amino acid, the enzymatically active domain of the toxin, and therefore, it is

not toxic. Id. at 12, 28, 31; see also Pet. Ex. 88 at 1.28

Again, based on his own research, Dr. Steinman determined that molecular mimicry

might occur between CRM197 and Contactin-1, a molecule that has been identified in patients

with GBS. Pet. Ex. 57 at 21. Dr. Steinman relied on Miura et al., a study done on patients with

CIDP. Id. (citing Pet. Ex. 79). Miura et al. focused their research on patients with CIDP, but

used sera from patients with GBS, MS, and healthy patients as controls. Pet. Ex. 79 at 2. They

found that five of the 200 patients with GBS had anti-Contactin-1 Immunoglobulin G (“IgG”)

antibodies. Id. at 3, 6 tbl.2.

The Miura et al. authors explained the theory of pathogenesis relevant to Dr. Steinman’s

theory, as it relates to Contactin-1. They stated,

[c]ell adhesion molecules play a crucial role in the formation of the nodes

of Ranvier and in the rapid propagation of the nerve impulses along myelinated

axons. In the peripheral nerves, the domain organization of myelinated axons

depends on specific axo-glial contacts between the axonal membrane and

Schwann cells at nodes, paranodes[,] and juxtaparanodes.

Pet. Ex. 79 at 2.

Miura et al. identified Contactin-1 (CNTN1) as one of the targets of autoantibodies in

some patients with GBS. Pet. Ex. 79 at 3. Based on this information about the potential

26

Protein carrier “CRM197 is a nontoxic variant of diphtheria toxin isolated from cultures of

Corynebacterium diphtheriae strain C7 (β197) grown in a casamino acids and yeast extract-

based medium.” Pet. Ex. 69 at 24 (Prevnar 13 package insert).

27

Contactin-1, or CNTN1, “is a key axonal adhesion molecule, which interacts with CNTNAP1

(previously known as Caspr1) on the axon and neurofascin-155 on the glial side, and is essential

for the formation of the paranodal septate-like junction.” Pet. Ex. 79 at 2 (Yumako Miura et al.,

Contactin I IgG4 Associates to Chronic Inflammatory Demyelinating Polyneuropathy with

Sensory Ataxia, 138 Brain 1484 (2015)).

28

Michael Bröker et al., Biochemical and Biological Characteristics of Cross-Reacting Material

197 (CRM197), a Non-Toxic Mutant of Diphtheria Toxin: Use as a Conjugation Protein in

Vaccines and Other Potential Clinical Applications, 39 Biologicals 195 (2011).

13

importance of Contactin-1, Dr. Steinman conducted a BLAST29 search to determine whether

there was homology between CRM197 in the vaccine and Contactin-1.30 Pet. Ex. 57 at 21. He

found a sequence31 that “might be capable of inducing a neuroinflammatory disease.” Id. at 27.

He found it is an epitope in diphtheria toxin, which provides the basis for CRM197. Id. at 28-30.

After additional research, Dr. Steinman identified another sequence32 that “has known cross-

reactivity with epitopes described in humans” on the Corynebacterium diphtheriae microbe. Id.

at 30.

Dr. Steinman opined the two sequences he found were significant due to five identical

amino acids in a nervous system protein. Pet. Ex. 57 at 21-22. He cited a number of papers,

including some that he authored or co-authored, to support his opinion that homology of just five

amino acids can induce an immune response consistent with his theory here. Id. For example, in

his 1993 paper,33 Dr. Steinman wrote that “[a]n autoimmune response can begin even if the

molecular mimicry is not quite exact.” Pet. Ex. 87 at 4. He cited the Gautam et al. studies34 for

the proposition that autoimmune encephalomyelitis could be induced with only five amino acids

identical to myelin basic protein, out of short sequences of 10 amino acids. Pet. Ex. 57 at 21.

(citing Pet. Exs. 80-82, 87).

In summary, Dr. Steinman averred that this theory provides “actual detailed data for

molecular mimics in the CRM in the Prevnar 13 vaccine” and how “these mimics could trigger

inflammatory neuropathy culminating in GBS.” Pet. Ex. 57 at 31 (emphasis omitted).

29

A BLAST (Basic Local Alignment Search Tool) search “finds regions of similarity between

biological sequences. The program compares nucleotide or protein sequences to sequence

databases and calculates the statistical significance.” BLAST, https://blast.ncbi.nlm.nih.gov/

Blast.cgi (last visited Nov. 1, 2023).

30

For a complete explanation of Dr. Steinman’s investigation, including his discussion on the

number of amino acids required for homology relevant to molecular mimicry as well as the

procedure he followed in conducting his BLAST searches, see Pet. Ex. 57 at 21-27.

31

The sequence is “WEQAKALSVE,” which “has five of ten identical amino acids.” Pet. Ex.

57 at 27.

32

The second sequence is “EYMAQACAGNRVRR.” Pet. Ex. 57 at 30.

33

Lawrence Steinman, Autoimmune Disease, 269 Sci. Am. 106 (1993).

34

Anand M. Gautam et al., A Polyalanine Peptide with Only Five Native Myelin Basic Protein

Residues Induces Autoimmune Encephalomyelitis, 176 J. Experimental Med. 605 (1992); Anand

M. Gautam et al., Minimum Structural Requirements for Peptide Presentation by Major

Histocompatibility Complex Class II Molecules: Implications in Induction of Autoimmunity, 91

Immunology 767 (1994); Anand M. Gautam et al., A Viral Peptide with Limited Homology to a

Self Peptide Can Induce Clinical Signs of Experimental Autoimmune Encephalomyelitis, 161 J.

Immunology 60 (1998). Dr. Steinman is a named author in all of these papers.

14

3. Medical Literature

After setting forth his theories, Dr. Steinman offered additional medical literature, a case

report, and a paper from the Centers for Disease Control and Prevention (“CDC”) in support of

his opinions. Pet. Ex. 57 at 32. He cited a case report published by Ravishankar35 about a

patient who developed GBS about one month after her pneumococcal vaccination. Id. (citing

Pet. Ex. 90 at 1). He also cited a 2016 CDC publication authored by Haber et al.36 reporting 11

cases of GBS after the Prevnar 13 vaccination. Id. (citing Pet. Ex. 91). There were 11 reports of

GBS, one in patients aged 19 to 64, and 10 in the age range of 65 and older. Pet. Ex. 91 at 3

tbl.2a, 4 tbl.2b. Median onset was nine days post-vaccination and median patient age was 68

years. Id. at 4. Dr. Steinman stated that the paper “reinforces the likelihood that molecular

mimicry following Prevnar 13 vaccination can cause GBS.” Pet. Ex. 57 at 32 (citing Pet. Ex.

91).

Dr. Steinman concluded that GBS is “a relatively rare illness. Numerous vaccines

including Prevnar 13 can in rare instances through the theory of molecular mimicry cause GBS.”

Pet. Ex. 57 at 32.

ii. Althen Prong Two

Regarding a logical sequence of cause and effect, Dr. Steinman stated that there is “a

logical sequence of cause and effect showing the vaccination was the reason for the injury,”

since it “has constituents that induce antibodies known to cross-react with myelin and that are

found in patients with GBS.” Pet. Ex. 57 at 33.

Although Petitioner had an episode of diarrhea before he became ill, he tested negative

for Clostridioides difficile, and was not tested for Campylobacter jejuni. Pet. Ex. 57 at 32. Dr.

Steinman opined that even if Petitioner’s diarrhea “contributed to triggering [Petitioner’s] GBS,

the Prevnar 13 vaccine was a substantial factor in triggering [Petitioner’s] GBS.” Id. at 32-33.

iii. Althen Prong Three

Petitioner received the Prevnar 13 vaccination on April 12, 2017, and Dr. Steinman stated

that according to Dr. Diaz’s note, Petitioner had GBS by April 27, 2017. Pet. Ex. 57 at 32. Dr.

Steinman further opinioned that this onset was consistent with “the timing known for GBS and

the 1976 swine flu immunization, often used as a surrogate in such cases regarding timing.” Id.

35

Nidhi Ravishankar, Guillain-Barre Syndrome Following PCV Vaccine, 2 Clinics Surgery 1413

(2017).

36

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–December 31, 2015, 34 Vaccine 6330 (2016). This is

also cited as Resp. Ex. A, Tab 8.

15

(citing Pet. Ex. 92).37 He also cited the Haber et al. article in support of his opinion that

Petitioner’s temporal association between vaccination and GBS onset was appropriate given his

proposed mechanism of molecular mimicry. Id. (citing Pet. Ex. 91). Haber et al. reported a

median onset of nine days with a range of two to 34 days. Pet. Ex. 91 at 4. Dr. Steinman

concluded that the temporal relationship criteria of Althen prong three was fulfilled based on this

interval. Pet. Ex. 57 at 33.

2. Respondent’s Expert, Dr. Dara G. Jamieson38

a. Background and Qualifications

Dr. Jamieson is a board-certified neurologist licensed in New York. Resp. Ex. V at 2.

She received her medical degree from the University of Pennsylvania, followed by a neurology

residency and a cerebrovascular fellowship at the University of Pennsylvania Hospital. Resp.

Ex. U at 1. Dr. Jamieson was a practicing neurologist for 32 years before transitioning to a

voluntary faculty appointment in 2018. Id. She is currently a Clinical Associate Professor of

Neurology at Weill Cornell Medicine, where she teaches medical students in neurology courses

and clinical inpatient clerkships, as well as lectures to residents and fellows. Id. She has also

lectured extensively nationally and internationally on neurological topics. Id. at 2; Resp. Ex. V

at 4-10. Dr. Jamieson serves on several editorial boards, including the Journal of

Neuroimmunology, Current Treatment Opinions in Neurology, and Neurology Alert. Resp. Ex.

U at 1-22. She has authored or co-authored numerous publications in peer reviewed journals as

well as authored books and book chapters on various neurological topics. Id.; Resp. Ex. V at 10-

14.

b. Opinion

Dr. Jamieson offered opinions from the perspective of a neurologist, and deferred to

Respondent’s immunologist, Dr. He, as to the immunological issues. See Resp. Ex. U at 10.

i. Althen Prong One

Dr. Jamieson first opined that “there is no epidemiological evidence that Prevnar [13] is a

trigger for GBS.” Resp. Ex. U at 12. Dr. Jamieson cited studies that purported to show that

there is no association between vaccinations, including pneumococcal vaccines, and GBS. A

brief summary of Dr. Jamieson’s opinions related to these studies is set forth below.

37

Lawrence B. Schonberger et al., Guillain Barré Syndrome Following Vaccination in the

National Influenza Immunization Program, United States, 1976-1977, 110 Am J. Epidemiology

105 (1979).

38

Dr. Jamison submitted one expert report. Resp. Ex. U.

16

Dr. Jamieson cited Baxter et al., who evaluated the relationship between GBS and

vaccinations, including the 23-valent pneumococcal polysaccharide vaccine. Resp. Ex. Z at 1, 4.

The authors reviewed records of 415 hospitalized patients diagnosed with GBS from 1995 to

2006. Id. at 1. Of these, 25 had received a vaccine within a six-week period prior to onset of

their GBS. Id. at 4. The vaccines included flu (18 patients), 23-valent pneumococcal

polysaccharide (two patients),39 tetanus-diphtheria combination (three patients), and hepatitis A

and B (three patients). Id. “[U]sing a case-centered method to control for seasonality and other

time-varying confounders, [they] found no evidence of an increased risk of GBS following any

vaccination.” Id. at 5. The authors acknowledged, however, that the study had “limited power to

fully assess the risk of GBS following vaccination due to the rarity of the outcome.” Id. at 7.

And they concluded that the results “provide reassurance that the risk of GBS following any

vaccine . . . is extremely low.” Id.

Dr. Jamieson also discussed the study by Chen et al.40 Resp. Ex. U at 8 (citing Resp. Ex.

AA at 1). She asserted that this study conducted between 2011 and 2015 in three Chinese cities

found no association between vaccinations and the risk of GBS in pediatric or adult patients. Id.

Specific to the pneumococcal vaccines, Dr. Jamieson cited Tseng et al.,41 which

compared adverse events between the Prevnar 13 vaccine and the 23-valent pneumococcal

polysaccharide vaccine. Resp. Ex. U at 9 (citing Resp. Ex. Q at 1). The authors concluded there

was no significantly increased risk of GBS after Prevnar 13 when compared with the 23-valent

pneumococcal polysaccharide vaccine. Id. (citing Resp. Ex. Q at 1).

Souayah et al.42 reviewed reports to the Vaccine Adverse Event Reporting System

(“VAERS”) in 2004 and found 54 cases of GBS post-vaccination, including one report of GBS

following the pneumococcal polyvalent vaccine, however, the onset interval was not provided.

Resp. Ex. BB at 1. Thus, Dr. Jamison did not find it to provide evidence of causation. Resp. Ex.

U at 9.

Haber et al. studied adverse event reports reported to VAERS in adults following the

Prevnar 13 vaccine from June 2012 to December 2015. Resp. Ex. U at 9 (citing Pet. Ex. 91).

During that time period, there were 2,976 total reports. Id. Most of the reports related to

39

Petitioner did not receive this vaccine. However, as evidenced by the package inserts, the

Prevnar 13 and 23-valent pneumococcal polysaccharide vaccines contain the same 13 bacterial

polysaccharides. See Pet. Exs. 69, 77.

40

Yong Chen et al., Vaccines and the Risk of Guillain-Barré Syndrome, 35 Eur. J. Epidemiology

363 (2020).

41

Hung Fu Tseng et al., Pneumococcal Conjugate Vaccine Safety in Elderly Adults, 5 Open

Forum Infectious Diseases ofy100 (2018).

42

Nizar Souayah et al., Guillain-Barre Syndrome After Vaccination in United States A Report

from the CDC/FDA Vaccine Adverse Event Reporting System, 24 Vaccine 5253 (2007).

17

injection site adverse events (injection site pain, redness, and swelling). Pet. Ex. 91 at 3 tbl.1.

There were 11 cases of GBS reported following the Prevnar 13 vaccination, and in ten of those,

the Prevnar 13 vaccine was the only vaccine administered. Id. at 4. One patient also received a

flu vaccine. Id. The authors concluded that their “data mining analysis noted no

disproportionate reporting for GBS.” Id. at 5. Dr. Jamieson criticized Dr. Steinman’s reliance

on Haber et al., particularly his opinion that it “reinforces the likelihood of molecular mimicry.”

Resp. Ex. U at 11 (quoting Pet. Ex. 57 at 32). Instead of supporting Dr. Steinman’s theory, Dr.

Jamieson believed that the occurrence of GBS is “a coincidental association with an almost

universal, annually recurring event, be it vaccination or paying taxes, [and] is to be expected.”

Id.

In Cordonnier et al.,43 immunocompromised patients (they had undergone stem cell

transplant) were administered Prevnar 13 and 23-valent pneumococcal polysaccharide vaccines.

Resp. Ex. DD at 1. One patient developed GBS 29 days after the fourth dose of Prevnar 13 and

one day after the 23-valent pneumococcal polysaccharide vaccine. Resp. Ex. DD at 7. Due to

the patients’ comorbidities, exposure to infections, and other confounders, the authors were

unable to establish “a clear causal relationship” between vaccination and GBS. Resp. Ex. U at 9-

10 (quoting Resp. Ex. DD at 9).

Dr. Jamieson also cited the Ravishankar case report referenced by Dr. Steinman and

argued that the patient did not have GBS since her illness was progressive and the interval

between onset and nadir of weakness exceeded the Brighton criteria for GBS. Resp. Ex. U at 10.

Thus, Dr. Jamieson argued that the patient had an “undiagnosed prolonged neurological

disorder,” not GBS, and there was no association between her vaccinations and illness. Id. Dr.

Jamieson criticized Dr. Steinman’s use of the case report due to the issue she identified with the

diagnosis of GBS. Id. at 10-11. Dr. Jamieson also did not agree that the case report provided

evidence that the Prevnar vaccine was a substantial factor that triggered GBS in the Petitioner.

Id. at 11.

ii. Althen Prong Two

Dr. Jamieson agreed that Petitioner was properly diagnosed with GBS. Resp. Ex. U at

11. She opined that in the winter months of 2016 and 2017, Petitioner had respiratory infections

and flu-like symptoms, and that these types of infections are recognized as triggers for GBS. Id.

She further opined that, more likely than not, Petitioner’s preceding respiratory infections were

the cause of his GBS. Id. at 11-12. Dr. Jamieson explained that a “proven trigger of GBS by an

infection is a much more reasonable causation for [Petitioner’s] GBS than [] an unproven trigger

by a vaccine.” Id. at 12. She did not identify the date of Petitioner’s antecedent infection which

she alleged caused Petitioner’s GBS or provide any other specific information about the infection

that she believed caused Petitioner’s GBS.

43

Catherine Cordonnier et al., Immunogenicity, Safety, and Tolerability of 13-Valent

Pneumococcal Conjugate Vaccine Followed by 23-Valent Pneumococcal Polysaccharide

Vaccine in Recipients of Allogeneic Hematopoietic Stem Cell Transplant Aged ≥ 2 Years: An

Open-Label Study, 61 Clinical Infectious Disease 313 (2015).

18

Regarding the duration and severity of Petitioner’s symptoms, she agreed that he had

symptoms of GBS longer than six months, but she asserted that at six months, Petitioner’s

symptoms were “mild and non-disabling, and primarily sensory. Despite fluctuations in his

persistent sensory symptoms,” Dr. Jamison opined that Petitioner was not disabled. Resp. Ex. U

at 11.

iii. Althen Prong Three44

Dr. Jamieson agreed that two weeks after the Prevnar 13 vaccination administered on

April 12, 2017, Petitioner had sensory symptoms of GBS that progressed to “mild weakness and

areflexia.” Resp. Ex. U at 11. She did not refute Petitioner’s assertion that there was an

appropriate temporal association between Petitioner’s Prevnar 13 vaccination and his GBS.

3. Respondent’s Expert, Dr. You-Wen He45

a. Background and Qualifications

Dr. He is currently a Professor of Immunology at the Department of Immunology at

Duke University Medical Center. Resp. Ex. A at 1. Dr. He received his M.D. from the Fourth

Military Medical University in Xian, China, and his Ph.D. in Microbiology and Immunology

from the University of Miami School of Medicine in Miami, Florida. Resp. Ex. T at 1. His

research areas include “innate and adaptive immunity against viral and bacterial infections[,] as

well as tumors.” Resp. Ex. A at 1. He has conducted research on human immune responses to

viral infections and is currently a Co-Principal Investigator for clinical trials focusing on cancer

immunotherapy. Id. Dr. He has reviewed National Institutes of Health (“NIH”) studies, serves

44

Dr. Jamison also opined that the onset of Petitioner’s GBS was about half a year after his flu

vaccination, which is too long to support “any contention that there was a connection” between it

and his GBS. Resp. Ex. U at 11. Petitioner no longer asserts that there is a causal connection

between his flu vaccine and GBS. See Pet. Br. at 10 n.1.

45

Dr. He submitted three expert reports. Resp. Exs. A, D, E. Additionally, in Dr. He’ s expert

reports, he responded to opinions offered by Petitioner’s initial expert, Gary Pekoe, Ph.D.

However, Petitioner stated in his brief that “his claim relies on [Dr.] Steinman’s expert report

and medical theory that the Prevnar 13 vaccination on April 12, 2017[] caused his vaccine

injury.” Pet. Br. at 10 n.1. “Accordingly, Petitioner will not be discussing nor submitting any

theories put forth by Petitioner’s initial expert, [Dr. Pekoe] regarding vaccinations received

outside of temporal relevance to Petitioner’s GBS (i.e. the Flulaval Quad vaccine).” Id.

Therefore, the undersigned will not discuss Dr. He’s opinions offered in response to Dr. Pekoe’s

opinions but will limit her discussion and analysis to the Prevnar 13 vaccination as proffered by

Dr. Steinman. Dr. He’s opinions in response to Dr. Steinman’s opinions are discussed in his

third report. Resp. Ex. E. While the undersigned has reviewed and considered all of Dr. He’s

opinions, as well as all of the medical literature cited by Dr. He in all three of his reports, this

Ruling focuses on the opinions most relevant here, responsive to Dr. Steinman.

19

on editorial boards, and has authored or co-authored numerous publications. Id. at 1-2; Resp. Ex.

T at 2-3, 7-16.

b. Opinion

Dr. He did not dispute Petitioner’s diagnosis of GBS. In his summary of the medical

records, Dr. He acknowledged that Petitioner was admitted to the hospital on April 29, 2017, was

diagnosed with GBS, and received treatment for GBS. See Resp. Ex. A at 3.

i. Althen Prong One

In his first expert report, Dr. He acknowledged that molecular mimicry may play a role in

the pathogenesis of GBS. Resp. Ex. A at 3. He stated, “[a]lthough the pathological mechanisms

by which GBS develops remain to be firmly established, cross-reactive autoantibodies may play

some roles in its immunopathogenesis.” Id. He also agreed that the “cross-reactive antibodies

may attack peripheral nerves and roots and cause demyelination and axonal damage.” Id.

In his second report, however, Dr. He backed away from his support of molecular

mimicry, calling it “an old theory [that] has been strongly challenged by recent scientific

evidence from large sequencing of proteomes of microbial pathogens.” Resp. Ex. D at 7. Based

on a paper by Kanduc et al.,46 Dr. He asserted that “viral and human proteomes have massive

peptide sharing,” which would cause “a 100% autoimmune disease rate in the general population

after either infection or vaccination” if molecular mimicry was a causal mechanism. Id. (citing

Resp. Ex. D, Tab 4). Dr. He concluded that “mere sequence similarity cannot be used to . . .

[conclude] that vaccines cause autoimmune diseases.” Id.

In his third expert report, Dr. He provided responsive comments about Dr. Steinman’s

two theories, described below.

1. Phosphoglycerol in Serotypes 18C and 23F

First, Dr. He acknowledged that Dr. Steinman proposed that phospholipids in the human

myelin sheath was a potential target in GBS. Resp. Ex. E at 2. Citing Gilburd et al. and Nakos

et al., Dr. Steinman showed that anti-phospholipids have been detected in GBS patients. Pet. Ex.

57 at 13-14. In response, Dr. He emphasized the conclusion in Gilburd et al. stated that “these

autoantibodies are probably produced as a result of the myelin damage rather than [the] cause

[of] demyelination.” Resp. Ex. E at 3 (quoting Pet. Ex. 70 at 1).

Dr. He did not take issue with Dr. Steinman’s description of foundational data showing

that the glycerol phosphate side chains in 18C and 23F of the Prevnar 13 vaccine “could be

targets for human antibodies.” Resp. Ex. E at 4. Specifically, as to Dr. Steinman’s opinions

related to 23F, Dr. He stated, “[t]hese are elegant studies. I completely agree that the cited

studies unequivocally demonstrate[] human immune responses to the serotype 23F and its

46

Darja Kanduc et al., Massive Peptide Sharing Between Viral and Human Proteomes, 29

Peptides 1755 (2008).

20

phosphoglycerol group.” Id. at 5. However, Dr. He disagreed there was evidence that “cross-

reactive antibodies are induced by [Prevnar 13] vaccination.” Id. He also opined that even if

there was cross-reactivity, there is no evidence that such would lead to pathology and cause

GBS. Id. at 5-6.

2. CRM197 and Contactin-1

The second homology described by Dr. Steinman was between the protein carrier in the

vaccine, CRM197, and Contactin-1, a protein found in humans. Pet. Ex. 57 at 16. Prevnar 13 is a

conjugate vaccine in which the individual polysaccharides of the capsular antigens of S.

pneumoniae are linked to a CRM197 protein. Id. at 7.

In response to this theory, Dr. He observed that “Dr. Steinman spent a large effort here to

search for sequence homologies and cross-reactive epitopes with two important tools in

biomedical research: BLAST and the Immune Epitope Database (IEDB).” Resp. Ex. E at 11.

Dr. He continued noting that Dr. Steinman identified sequences with five amino acids that might

induce neuroinflammatory disease. Id. Relying on Raju et al., Dr. Steinman stated that “humans

have been shown to mount T cell responses to these regions of the diphtheria molecule.” Id.

(quoting Pet. Ex. 57 at 30). Dr. He explained, however, that this “demonstration of sequence

homologies between human proteins and microbial pathogen sequences is entirely expected due

to recent advances in genomic sequence technologies.” Id. at 12. Citing Kanduc et al., Dr. He

asserted that “an astonishing 90%” of five amino acid sequences “are widely . . . scattered

throughout the human proteome.” Id. (citing Resp. Ex. D, Tab 4). He concluded that “it is not

surprising to have sequence homologies between CRM197 and human proteins.” Id.

Additionally, Dr. He asserted that “cross reactivity of T cells and antibodies between self-

proteins and infectious agents is widely detectable.” Resp. Ex. E at 12. For this reason, Dr. He

asserted that three criteria established by the Institute of Medicine (“IOM”),47 must be fulfilled

in order to conclude that molecular mimicry contributes to disease. Id. (citing Resp. Ex. P).

These three criteria are:

(1) a susceptible host whose genetic background and adaptive immune responses

allows emergence of self-reactive immunity, (2) exposure to an exogenous agent

which expresses antigens that are immunologically similar to self-antigen(s), and

(3) a host immune response to the exogenous agent that cross-reacts with

biologically relevant host tissue structures and causes tissue damage and clinical

disease.

Id. (quoting Resp. Ex. P at 4).

Further, Dr. He quoted additional limitations from the IOM, including that linear

homology or similar conformational structure are insufficient to support molecular mimicry.

47

Inst. of Med., Evaluating Biological Mechanisms of Adverse Events, in Adverse Effects of

Vaccines: Evidence and Causality 57 (Kathleen Stratton et al. eds., 2012). The IOM is now the

National Academy of Medicine.

21

Resp. Ex. E at 12. He also argued that in vitro demonstration of cross-reacting antibodies is also

not enough proof of molecular mimicry. Id. Instead, there must be an “in vivo pathogenic

autoimmune attack” to demonstrate “local binding of antibody with activation . . . of []

pathogenic [] mechanisms in a biologically relevant tissue site.” Id. (quoting Resp. Ex. P at 4-

5).

3. Medical Literature

Next, Dr. He responded to the literature filed by Petitioner. Regarding the Ravishankar

paper, Dr. He criticized the long temporal association, the publication of the case in two

different journals, and the low quality of the publications. Resp. Ex. E at 13. As for the paper

by Haber et al., Dr. He opined that the study used VAERS data, noting the “huge limitation”

with VAERS because “it is a passive reporting system and anyone can report.” Id. at 14. He

also argued that VAERS reports use “presumptive” diagnoses and do not account for alternative

causes. Id. Dr. He also addressed the Tseng et al. study, noting that the study did not show an

increased rate of adverse events after the Prevnar 13 vaccine as compared with the 23-valent

pneumococcal polysaccharide vaccine. Id. Lastly, Dr. He concluded that there is a “complete

lack of epidemiological evidence” between the Prevnar 13 vaccination and the development of

GBS. Id.

ii. Althen Prong Two

Dr. He disagreed that there was a logical sequence of cause and effect, arguing that

Petitioner had symptoms of an upper respiratory infection on February 27, 2017, and that this

infection “was a more likely trigger” of GBS than vaccination. Resp. Ex. E at 15-16.

According to Dr. He, infections are “fundamentally different from vaccinations in the

capability to induce immune responses.” Resp. Ex. E at 7. He explained the process whereby

infections trigger the host immune system in a manner that simulates a “much broader immune

response” than vaccines. Id. at 8. Dr. He also described the two major differences between

immune responses following infections as compared with vaccination. Id. at 7-8. Dr. He argued

that S. pneumoniae, “a gram-positive bacterium, is a common cause of [upper respiratory

infection].” Id. at 8 (emphasis omitted). Thus, he asserted that Petitioner’s upper respiratory

infection provided a “much stronger immune stimulus than his [Prevnar 13] vaccination.” Id.

Dr. He further opined that Petitioner’s upper respiratory symptoms occurred during a

timeframe that supports a causal association with GBS. Resp. Ex. E at 14-16.

iii. Althen Prong Three

Dr. He agreed with Dr. Steinman that there was an appropriate temporal association

between the Prevnar 13 vaccine the onset of Petitioner’s GBS. Resp. Ex. E at 14. Dr. He

referenced Dr. Steinman’s opinion based on Dr. Diaz’s records, where Dr. Diaz indicated that

Petitioner had GBS by April 27, 2017. See id. He also agreed with Dr. Steinman’s use of the

onset interval based on data from the 1976 swine flu immunization campaign, which Dr. He

agreed was “often used as a surrogate regarding triggering events” and GBS. Id. Dr. He further

22

agreed that it “is generally accepted that the 1976/H1N1 swine flu vaccine was associated with

increased risk for GBS,” and that the period of increased risk was up to 9- or 10-weeks

following vaccination. Id.

III. DISCUSSION

A. Standards for Adjudication

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-injured 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). 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 scientific or medical communities

to establish a logical sequence of cause and effect.” Capizzano v. Sec’y of Health & Hum.

Servs., 440 F.3d 1317, 1325 (Fed. Cir. 2006). Instead, Petitioner may satisfy his burden by

presenting circumstantial evidence and reliable medical opinions. Id. at 1325-26.

In particular, a 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). The

received vaccine, however, need not be the predominant cause of the injury. Shyface, 165 F.3d

at 1351. 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). However, if a petitioner fails to

establish a prima facie case, the burden does not shift. Bradley v. Sec’y of Health & Hum.

Servs., 991 F.2d 1570, 1575 (Fed. Cir. 1993).

“Regardless of whether the burden ever shifts to the [R]espondent, the special master

may consider the evidence presented by the [R]espondent in determining whether the [P]etitioner

has established a prima facie case.” Flores v. Sec’y of Health & Hum. Servs., 115 Fed. Cl. 157,

162-63 (2014); see also Stone v. Sec’y of Health & Hum. Servs., 676 F.3d 1373, 1379 (Fed. Cir.

2012) (“[E]vidence of other possible sources of injury can be relevant not only to the ‘factors

unrelated’ defense, but also to whether a prima facie showing has been made that the vaccine

was a substantial factor in causing the injury in question.”); de Bazan v. Sec’y of Health & Hum.

Servs., 539 F.3d 1347, 1353 (Fed. Cir. 2008) (“The government, like any defendant, is permitted

to offer evidence to demonstrate the inadequacy of the [P]etitioner’s evidence on a requisite

23

element of the [P]etitioner’s case-in-chief.”); Pafford, 451 F.3d at 1358-59 (“[T]he presence of

multiple potential causative agents makes it difficult to attribute ‘but for’ causation to the

vaccination. . . . [T]he Special Master properly introduced the presence of the other unrelated

contemporaneous events as just as likely to have been the triggering event as the vaccinations.”).

B. Causation

To receive compensation through the Program, Petitioner must prove either (1) that he

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

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

vaccination. See §§ 11(c)(1), 13(a)(1)(A); Capizzano, 440 F.3d at 1319-20. Petitioner must

show that the vaccine was “not only a but-for cause of the injury but also a substantial factor in

bringing about the injury.” Moberly, 592 F.3d at 1321 (quoting Shyface, 165 F.3d at 1352-53).

Because Petitioner does not allege he suffered a Table Injury, he must prove a vaccine he

received actually caused her injury. To do so, Petitioner must establish, by preponderant

evidence: “(1) a medical theory causally connecting the vaccination and the injury; (2) a logical

sequence of cause and effect showing that the vaccination was the reason for the injury; and (3) a

showing of a proximate temporal relationship between vaccination and injury.” Althen, 418 F.3d

at 1278.

The causation theory must relate to the injury alleged. 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). 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 special master must weigh

the submitted evidence and the testimony of the parties’ proffered experts and rule in Petitioner’s

favor when the evidence weighs in her 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).

Testimony that merely expresses the possibility—not the probability—is insufficient, by

itself, to substantiate a claim that such an injury occurred. See Waterman v. Sec’y of Health &

Hum. Servs., 123 Fed. Cl. 564, 573-74 (2015) (denying Petitioner’s motion for review and

noting that a possible causal link was not sufficient to meet the preponderance standard). The

Federal Circuit has made clear that the mere possibility of a link between a vaccination and a

petitioner’s injury is not sufficient to satisfy the preponderance standard. Moberly, 592 F.3d at

1322 (emphasizing that “proof of a ‘plausible’ or ‘possible’ causal link between the vaccine and

the injury” does not equate to proof of causation by a preponderance of the evidence); Boatmon

v. Sec’y of Health & Hum. Servs., 941 F.3d 1351, 1359-60 (Fed. Cir. 2019). While certainty is

24

by no means required, a possible mechanism does not rise to the level of preponderance.

Moberly, 592 F.3d at 1322; see also de Bazan, 539 F.3d at 1351.

IV. ANALYSIS

A. Causation

1. Althen Prong One

Under Althen prong one, Petitioner must set forth a medical theory explaining how the

received vaccine could have caused the sustained injury. Andreu v. Sec’y of Health & Hum.

Servs., 569 F.3d 1367, 1375 (Fed. Cir. 2009); Pafford, 451 F.3d at 1355-56. Petitioner’s theory

of causation need not be medically or scientifically certain, but it must be informed by a “sound

and reliable” medical or scientific explanation. Boatmon, 941 F.3d at 1359; see also Knudsen,

35 F.3d at 548; Veryzer v. Sec’y of Health & Hum. Servs., 98 Fed. Cl. 214, 257 (2011) (noting

that special masters are bound by both § 13(b)(1) and Vaccine Rule 8(b)(1) to consider only

evidence that is both “relevant” and “reliable”). If Petitioner relies upon a medical opinion to

support her theory, the basis for the opinion and the reliability of that basis must be considered in

the determination of how much weight to afford the offered opinion. See Broekelschen v. Sec’y

of Health & Hum. Servs., 618 F.3d 1339, 1347 (Fed. Cir. 2010) (“The special master’s decision

often times is based on the credibility of the experts and the relative persuasiveness of their

competing theories.”); Perreira v. Sec’y of Health & Hum. Servs., 33 F.3d 1375, 1377 n.6 (Fed.

Cir. 1994) (stating that an “expert opinion is no better than the soundness of the reasons

supporting it” (citing Fehrs v. United States, 620 F.2d 255, 265 (Ct. Cl. 1980))).

For the following reasons, the undersigned finds Petitioner has provided, by preponderant

evidence, a sound and reliable theory by which the Prevnar 13 vaccine can cause GBS, and

therefore, Petitioner has satisfied the first Althen prong.

Molecular mimicry has long been invoked as the causal mechanism for many different

autoimmune diseases, including GBS. Many of the articles filed in this case support the

mechanism as a leading hypothesis for the etiology of GBS. The theory has been extended from

infectious agents to vaccine-associated autoimmune illnesses, including GBS.

Molecular mimicry has been accepted as a sound and reliable theory in many

demyelinating conditions, including GBS, in the Vaccine Program, forming the basis for

petitioners to be entitled to compensation. See, e.g., Conte v. Sec’y of Health & Hum. Servs.,

No. 17-403V, 2020 WL 5743696, at *57 (Fed. Cl. Spec. Mstr. July 27, 2020) (noting the theory

of molecular mimicry in a GBS case is “well-established and well-settled in the Vaccine

Program”); Barone v. Sec’y of Health & Hum. Servs., No. 11-707V, 2014 WL 6834557, at *8-9

(Fed. Cl. Spec. Mstr. Nov. 12, 2014) (noting molecular mimicry “has been accepted in other

Program cases as a reliable medical explanation for how various autoimmune conditions could

develop after the receipt of different kinds of vaccinations”); Koller v. Sec’y of Health & Hum.

Servs., No. 16-439V, 2021 WL 5027947, at *18 (Fed. Cl. Spec. Mstr. Oct. 8, 2021); Pierson v.

Sec’y of Health & Hum. Servs., No. 17-1136V, 2022 WL 322836, at *31 (Fed. Cl. Spec. Mstr.

Jan. 19, 2022); Maloney v. Sec’y of Health & Hum. Servs., No. 19-1713V, 2022 WL 1074087

25

(Fed. Cl. Spec. Mstr. Mar. 17, 2022); Gross v. Sec’y of Health & Hum. Servs., No. 17-1075V,

2022 WL 9669651 (Fed. Cl. Spec. Mstr. Sept. 22, 2022).48

Dr. He proposes criteria from the IOM to establish whether a vaccine can cause GBS via

molecular mimicry. The criteria include a susceptible host (genetically and via host immune

responses), exposure to an exogenous agent that has “expresses antigens that are

immunologically similar to self-antigens,” and a “host immune response” that causes disease.

Resp. Ex. P at 4. Further, there must be evidence of an “in vivo pathogenic autoimmune attack”

and demonstration of the pathogenic mechanisms “in a biologically relevant tissue site.” Id.

Given the state of current scientific knowledge, it would not be possible for a petitioner to satisfy

these criteria. Further, fulfilment of these criteria would require scientific certainty, which is a

bar too high. See Knudsen, 35 F.3d at 549 (explaining that “to require identification and proof of

specific biological mechanisms would be inconsistent with the purpose and nature of the vaccine

compensation program”).

Moreover, Dr. He does not refute the scientific data or foundational evidence used by Dr.

Steinman to support his theories. Dr. Steinman has identified components of the vaccine that

could initiate development of antibodies that could cross-react with epitopes on peripheral nerve

myelin or axonal glycoproteins. He has identified components of the Prevnar 13 vaccine that

could trigger a human antibody response.

Regarding Petitioner’s theory based on phosphoglycerol in serotypes 18C and 23F in the

vaccine, Dr. Steinman produces papers to show that in MS, myelin phospholipids are targeted by

an immune response. He also shows that myelin is comprised of phospholipids, and that

phospholipids can serve as autoantigens in autoimmune disorders. He shows that patients with

GBS have autoantibodies to phospholipids. In the Gilburd et al. study, the autoantibodies were

thought to be due to myelin destruction. However, in Nakos et al., the researchers had a different

view. They suggested that anti-phospholipids either “play a role in pathogenesis of the

polyneuropathy or represent a part of a more extensive immunoreaction that takes place in

GBS.” Pet. Ex. 71 at 7. In summary, there is sound support from reputable medical studies for

each foundational aspect of Dr. Steinman’s phosphoglycerol theory.

There is also evidence to support Dr. Steinman’s second theory based on CRM197 and

Contactin-1. Dr. Steinman identified sequences of shared homology between the proteins in the

vaccine and those in Contactin-1.

Additionally, the causal theory proffered by Dr. Steinman here has previously been

accepted as sound and reliable in other cases, decided by different special masters, including the

undersigned. See, e.g., Maloney, 2022 WL 1074087; Koller, 2021 WL 5027947; Pierson, 2022

WL 322836; Gross, 2022 WL 9669651. While prior decisions are not binding on the

undersigned, they can be considered by the undersigned in forming her opinions. See Hanlon v.

Sec’y of Health & Hum. Servs., 40 Fed. Cl. 625, 630 (1998), aff’d, 191 F.3d 1344 (Fed. Cir.

48

The undersigned acknowledges that the first two cases in this string cite involve a different

vaccine, although the same illness.

26

1999); Boatmon, 941 F.3d at 1358. The undersigned agrees with the reasoning offered by her

colleagues in these other cases, and for many of the same reasons find the Petitioner’s theory

here sound and reliable and proven by preponderant evidence.

In another decision addressing the Prevnar 13 vaccine and GBS, the proffered causal

theory was unsupported by evidence, and the Chief Special Master found that Petitioner was not

entitled to compensation. Deshler v. Sec’y of Health & Hum. Servs., No. 16-1070V, 2020 WL

4593162, at *19 (Fed. Cl. Spec. Mstr. July 1, 2020).49 There, the Petitioner relied on molecular

mimicry, and suggested that there was homology between polysaccharide components of the

vaccine and the myelin sheath, but evidence was insufficient to establish the scientific soundness

of the theory. Id. at *19-21. Due to the lack of supportive evidence, the Respondent’s expert

was effective in establishing that the polysaccharides in the vaccine “do not share structural

homology with self-structures of the peripheral nervous system, and therefore do not contribute

to the pathogenesis of GBS.” Id. at *20. In contrast, the theories proffered here are more well-

developed and based on supportive foundational evidence from several scientific studies.

For these reasons, the undersigned finds that Petitioner has proven by preponderant

evidence a sound and reliable causal theory establishing that the Prevnar 13 vaccine can cause

GBS, satisfying Althen prong one.

2. Althen Prong Two

Under Althen prong two, Petitioner must prove by a preponderance of the evidence that

there is a “logical sequence of cause and effect showing that the vaccination 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 (internal citations omitted).

In evaluating whether this prong is satisfied, the opinions and views of the vaccinee’s

treating physicians are entitled to some weight. Andreu, 569 F.3d at 1367; Capizzano, 440 F.3d

at 1326 (“[M]edical records and medical opinion testimony are favored in vaccine cases, as

treating physicians are likely to be in the best position to determine whether a ‘logical sequence

of cause and effect show[s] that the vaccination was the reason for the injury.’” (quoting Althen,

418 F.3d at 1280)). Medical records are generally viewed as trustworthy evidence, since they are

created contemporaneously with the treatment of the vaccinee. Cucuras v. Sec’y of Health &

49

Since Deshler, the Chief Special Master and another special master have found against

compensation in other Prevnar 13/GBS cases. See Trollinger v. Sec’y of Health & Hum. Servs.,

No. 16-473V, 2023 WL 2521912, at *26 (Fed. Cl. Spec. Mstr. Feb. 17, 2023), review denied,

167 Fed. Cl. 127 (2023); Bielak v. Sec’y of Health & Hum. Servs., No. 18-761V, 2023 WL

35509, at *31-32 (Fed. Cl. Spec. Mstr. Jan. 3, 2023); Gamboa-Avila v. Sec’y of Health & Hum.

Servs., No. 18-925V, 2023 WL 6536207, at *25 (Fed. Cl. Spec. Mstr. Sept. 11, 2023);

McConnell v. Sec’y of Health & Hum. Servs., No. 18-1051V, 2022 WL 4008238, at *9 (Fed. Cl.

Spec. Mstr. Aug. 19, 2022). The undersigned acknowledges these cases but also notes that the

decisions of other special masters or Court of Federal Claims’ judges are not binding on special

masters. Boatmon, 941 F.3d at 1358; Hanlon, 40 Fed. Cl. at 630.

27

Hum. Servs., 993 F.2d 1525, 1528 (Fed. Cir. 1993). While the medical records and opinions of

treating physicians must be considered, they are not binding on the special master. § 13(b)(1)(B)

(specifically stating that the “diagnosis, conclusion, judgment, test result, report, or summary

shall not be binding on the special master or court”).

A 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 scientific or medical communities to establish a logical sequence of cause and

effect.” Capizzano, 440 F.3d at 1325. Instead, Petitioner may satisfy his burden by presenting

circumstantial evidence and reliable medical opinions. Id. at 1325-26.

There are three reasons why the undersigned finds preponderant evidence of a logical

sequence of cause and effect establishing that the Prevnar 13 vaccination administered to

Petitioner on April 12, 2017, was the cause of his GBS. First, Petitioner was appropriately

diagnosed with GBS, and Petitioner has proffered a sound and reliable mechanism of vaccine

causation.

Second, Petitioner’s treating physician, Dr. Diaz, offered evidence in support of vaccine

causation. In a follow-up appointment with Dr. Diaz on July 12, 2017, Petitioner was noted to

be improving, although he continued to have facial and throat numbness. On examination,

Petitioner had strength of 4/5 in all four extremities, however, he had no deep tendon reflexes

and decreased sensation in his distal legs and feet. Petitioner reported April 25, 2017 as the

onset of his symptoms associated with GBS. Dr. Diaz noted that “[b]ased on the timing and

sequence of events, this patient[’s] GBS is most likely secondary to the vaccinations received on

April 12, 2017.” Pet. Ex. 33 at 58.

The undersigned finds that this statement by Dr. Diaz constitutes circumstantial evidence

that he associated the Prevnar 13 vaccination administered on April 12, 2017 with the

development of Petitioner’s GBS.

Third, although Dr. He argues that Petitioner’s February 2017 upper respiratory infection

is the likely cause of Petitioner’s GBS, the undersigned does not find this opinion is supported by

preponderant evidence. Moreover, Dr. He did not state his opinion as to alternate cause to a

reasonable degree of probability.

The records establish that on February 27, 2017, Petitioner was seen by his primary care

provider for a cough, nasal congestion, body aches, and headaches. Flu testing was negative.

Petitioner was diagnosed with an upper respiratory infection and was treated with antibiotics (Z-

Pak), Albuterol inhaler, and Robitussin.

Petitioner received his Prevnar 13 vaccination on April 12, 2017. Approximately two

weeks later, on April 27, 2017, Petitioner complained of numbness in his hands, feet, and lips

that began two days before. Petitioner presented to the hospital on April 29, 2017, with

numbness in his feet, ankles, wrists, and hands. In the history, there is no mention of any recent

infection. There is no reference to cough, cold, sore throat, or other upper respiratory illness.

Petitioner had no nausea, vomiting, or abdominal pain. On April 30, 2017, Petitioner was seen

28

by neurologist, Dr. Rehman. Dr. Rehman wrote, “about [two] weeks ago” Petitioner “had a

pneumonia vaccine.” Pet. Ex. 30 at 86. Dr. Rehman did not mention any antecedent illness or

infection. Dr. Rehman’s assessment stated that Petitioner had two vaccinations (pneumonia and

shingles) two weeks ago, “consider the possibility of [GBS].” Id. at 87. This note indicates that

Dr. Rehman associated the vaccination with the potential diagnosis of GBS. Dr. Rehman did not

document any association between Petitioner’s symptoms and any illness or infection.

Petitioner was discharged on May 1, 2017, after his lumbar puncture, and resulting

cerebrospinal fluid (“CSF”) results were normal. Petitioner returned to the hospital on May 2,

2017, with worsening symptoms and was diagnosed with GBS. On admission, history

documented that Petitioner had no fevers or chills, and there is no mention of a prior illness or

infection. There is no reference to coughing, fever, sore throat, or other symptoms of an upper

respiratory illness. Daily progress notes from the date of admission until discharge (May 2 to

May 9) do not reference any prior respiratory infection or infection during Petitioner’s

hospitalization.

Diagnostic testing done during the hospital admission does not show evidence of

infection. Lumbar puncture performed on May 3, 2017 revealed CSF elevated protein of 166

(normal 15-45) consistent with GBS, but white blood cell count was normal at 2 (normal 0-5).

Pet. Ex. 30 at 681. CSF gram stain showed no bacterial growth. Id. at 684-85. Blood culture

drawn on May 5, 2017 also revealed no growth. Id. at 689.

In summary, Petitioner’s medical records, physician notes, and diagnostic workup did not

identify an infectious or alternate cause of Petitioner’s GBS. The only reference to an antecedent

event was related to Petitioner’s vaccinations on April 12, 2017. The opinions of treating

physicians are generally more reliable because they are created contemporaneously with the

treatment of the vaccinee. Cucuras, 993 F.2d at 1528.

In conclusion, the undersigned finds that Petitioner has proven by preponderant evidence

a logical sequence of cause and effect establishing that the Prevnar 13 vaccination caused his

GBS and has satisfied the second Althen prong.

3. 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. That phrase has been

defined as a “medically acceptable temporal relationship.” Id. A petitioner must offer

“preponderant proof that the onset of symptoms occurred within a timeframe for which, given

the medical understanding of the disorder’s etiology, it is medically acceptable to infer

causation-in-fact.” de Bazan, 539 F.3d at 1352. The explanation for what is a medically

acceptable time frame must also coincide with the theory of how the relevant vaccine can cause

the injury alleged (under Althen Prong One). Id.; Koehn v. Sec’y of Health & Hum. Servs., 773

F.3d 1579, 1243 (Fed. Cir. 2014); Shapiro, 101 Fed. Cl. at 542 (2011), recons. den’d after

remand, 105 Fed. Cl. 353 (2012), aff’d mem., 503 F. App’x 952 (Fed. Cir. 2013).

29

Here, Respondent’s experts do not disagree that there is a temporal association between

Petitioner’s vaccination and onset of GBS. Petitioner received his Prevnar 13 vaccination on

April 12, 2017, and presented with symptoms on April 27. Onset was approximately two weeks

after vaccination.

This time frame from vaccination to the initial manifestation of symptoms is appropriate

given the theory of molecular mimicry, as demonstrated in the Haber et al. article, which

reported 11 cases of GBS following a Prevnar 13 vaccine, with a median onset interval of nine

days. This temporal association is also consistent with the onset period of three to 42 days as set

forth in the Vaccine Injury Table for GBS following flu vaccination. 42 C.F.R. §

100.3(a)(XIV)(D).

Further, this time frame has been acknowledged as appropriate in other Vaccine Program

cases in which molecular mimicry has been proffered as the causal mechanism. See, e.g.,

Maloney, 2022 WL 1074087, at *36 (finding a GBS onset of seven days after Prevnar 13

vaccination to be appropriate); Koller, 2021 WL 5027947, at *57 (finding a GBS onset of 12

days after Prevnar 13 vaccination to be “within the medically accepted timeframe consistent with

[P]etitioner’s theory of molecular mimicry [and] that has been accepted in other Vaccine

Program cases”); Barone, 2014 WL 6834557, at *13 (“[S]pecial masters have never gone beyond

a two-month (meaning eight week) interval in holding that a vaccination caused a demyelinating

illness.”); Gross, 2022 WL 9669651, at *38-39 (finding a GBS onset of 13 days after Prevnar 13

vaccination to be appropriate).

Therefore, undersigned finds that Petitioner has met her burden of proof as to Althen

prong three.

V. CONCLUSION

Based on the record, and for the reasons discussed above, the undersigned finds there is

preponderant evidence to satisfy all three Althen prongs and to establish that Petitioner’s Prevnar

13 vaccination caused his GBS. Thus, the undersigned finds that Petitioner is entitled to

compensation. A separate damages order will issue.

IT IS SO ORDERED.

s/Nora Beth Dorsey

Nora Beth Dorsey

Special Master

30