Bartoszek v. Secretary of Health and Human Services

In the United States Court of Federal Claims

OFFICE OF SPECIAL MASTERS

No. 17-1254V

Filed: August 27, 2024

Special Master Horner

WILLIAM BARTOSZEK,

Petitioner,

v.

SECRETARY OF HEALTH AND

HUMAN SERVICES,

Respondent.

Anne Carrion Toale, Maglio Christopher and Toale, PA, Sarasota, FL, for petitioner.

Neil Bhargava, U.S. Department of Justice, Washington, DC, for respondent.

RULING ON ENTITLEMENT 1

On September 14, 2017, petitioner, William Bartoszek, filed a petition under the

National Childhood Vaccine Injury Act, 42 U.S.C. § 300aa-10, et seq. (2012), 2 alleging

that he suffered Guillain-Barré Syndrome (“GBS”) caused-in-fact by a Prevnar 13

vaccination he received on July 13, 2016. (ECF No. 1.) For the reasons set forth

below, I conclude that petitioner is entitled to an award of compensation.

I. Applicable Statutory Scheme

Under the National Vaccine Injury Compensation Program, compensation

awards are made to individuals who have suffered injuries after receiving vaccines. In

general, to gain an award, a petitioner must make a number of factual demonstrations,

including showing that an individual received a vaccination covered by the statute;

received it in the United States; suffered a serious, long-standing injury; and has

1

Because this document contains a reasoned explanation for the action taken in this case, it must be

made publicly accessible and will be posted 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 document 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, I agree that the identified material fits within this definition, I will redact such material from

public access.

2

Within this ruling, all citations to § 300aa will be the relevant sections of the Vaccine Act at 42 U.S.C. §

300aa-10-34.

1

received no previous award or settlement on account of the injury. Finally – and the key

question in most cases under the Program – the petitioner must also establish a causal

link between the vaccination and the injury. In some cases, the petitioner may simply

demonstrate the occurrence of what has been called a “Table Injury.” That is, it may be

shown that the vaccine recipient suffered an injury of the type enumerated in the

“Vaccine Injury Table,” corresponding to the vaccination in question, within an

applicable time period following the vaccination also specified in the Table. If so, the

Table Injury is presumed to have been caused by the vaccination, and the petitioner is

automatically entitled to compensation, unless it is affirmatively shown that the injury

was caused by some factor other than the vaccination. § 300aa-13(a)(1)(A)-(B); § 300

aa-11(c)(1)(C)(i); § 300aa-14(a).

In many cases, however, the vaccine recipient may have suffered an injury not of

the type covered in the Vaccine Injury Table. In such instances, an alternative means

exists to demonstrate entitlement to a Program award. That is, the petitioner may gain

an award by showing that the recipient’s injury was “caused-in-fact” by the vaccination

in question. § 300aa-11(c)(1)(C)(ii). In such a situation, of course, the presumptions

available under the Vaccine Injury Table are inoperative. The burden is on the

petitioner to introduce evidence demonstrating that the vaccination actually caused the

injury in question. Althen v. Sec’y of Health & Human Servs., 418 F.3d 1274, 1278

(Fed. Cir. 2005); Hines ex rel. Sevier v. Sec’y of Health & Human Servs., 940 F.2d

1518, 1525 (Fed. Cir. 1991).

The showing of “causation-in-fact” must satisfy the “preponderance of the

evidence” standard, the same standard ordinarily used in tort litigation. § 300aa-

13(a)(1)(A); see also Althen, 418 F.3d at 1279; Hines, 940 F.2d at 1525. Under that

standard, the petitioner must show that it is “more probable than not” that the

vaccination was the cause of the injury. Althen, 418 F.3d at 1279 (citations omitted).

The petitioner need not show that the vaccination was the sole cause of the injury or

condition but must demonstrate that the vaccination was at least a “substantial factor” in

causing the condition and was a “but for” cause. Shyface ex rel. Shyface v. Sec’y of

Health & Human Servs., 165 F.3d 1344, 1352 (Fed. Cir. 1999). Thus, the petitioner

must supply “proof of a logical sequence of cause and effect showing that the

vaccination was the reason for the injury;” the logical sequence must be supported by

“reputable medical or scientific explanation, i.e., evidence in the form of scientific

studies or expert medical testimony.” Althen, 418 F.3d at 1278 (citing Grant ex rel.

Grant v. Sec’y of Health & Human Servs., 956 F.2d 1144, 1148 (Fed. Cir. 1992)). A

petitioner may not receive a Vaccine Program award based solely on her assertions;

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

competent physician. § 300aa-13(a)(1).

In what has become the predominant framing of this burden of proof, the Althen

court described the “causation-in-fact” standard, as follows:

Concisely stated, Althen’s burden is to show by preponderant evidence

that the vaccination brought about her injury by providing: (1) a medical

2

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 proximate temporal relationship

between vaccination and injury. If Althen satisfies this burden, she is

entitled to recover unless the [government] shows, also by a

preponderance of the evidence, that the injury was in fact caused by

factors unrelated to the vaccine.

Althen, 418 F.3d at 1278 (citations omitted). The Althen court noted that a petitioner

need not necessarily supply evidence from medical literature supporting her causation

contention, so long as the petitioner supplies the medical opinion of an expert. Id. at

1279-80. That expert’s opinion must be “sound and reliable.” Boatmon v. Sec’y of

Health & Human Servs., 941 F.3d 1351, 1359-60 (Fed. Cir. 2019) (citing Knudsen ex

rel. Knudsen v. Sec’y of Health & Human Servs., 35 F.3d 543, 548-49 (Fed. Cir. 1994)).

The Althen court also indicated, however, that a Program fact-finder may rely upon

“circumstantial evidence,” which the court found to be consistent with the “system

created by Congress, in which close calls regarding causation are resolved in favor of

injured claimants.” 418 F.3d at 1280 (citations omitted).

Generally, respondent bears the burden of demonstrating the presence of any

alternative cause by preponderant evidence only if petitioner satisfies her prima facie

burden. § 300aa-13(a)(1)(B); Walther v. Sec’y of Health & Human Servs., 485 F.3d

1146, 1150 (Fed. Cir. 2007). However, respondent may also present evidence relating

to an alternative cause to demonstrate the inadequacy of petitioner’s evidence

supporting her case in chief. de Bazan v. Sec’y of Health & Human Servs., 539 F.3d

1347, 1352-53 (Fed. Cir. 2008). Nonetheless, petitioner does not bear the burden of

eliminating alternative causes where the other evidence on causation is sufficient to

establish a prima facie case under Althen. Walther, 485 F.3d at 1150-51.

II. Procedural History

This case was originally assigned to Special Master Millman. (ECF No. 4.)

Between September 2017 and December 2017, petitioner filed medical records and an

affidavit. (ECF Nos. 5-6, 11, 13, 16; Exs. 1-16.) In June of 2018, respondent filed his

Rule 4(c) Report arguing that the evidence presented did not meet petitioner’s burden

and recommending against compensation. (ECF No. 26.) Respondent did not dispute

petitioner’s GBS diagnosis but contended that vaccine causation was not supported.

(Id. at 6-8.) Petitioner subsequently filed additional medical records (ECF Nos. 27, 35;

Exs. 17, 50) and an expert report from neurologist Kazim A. Sheikh, M.D., with

supporting literature. (ECF Nos. 29-32; Exs. 18-49.) Respondent then filed an expert

report from immunologist Ross M. Kedl, Ph.D. (ECF Nos. 36-38; Exs. A-B.) In doubting

that petitioner suffered vaccine-caused GBS, Dr. Kedl opined, inter alia, that it was more

likely petitioner was suffering peripheral neuropathy due to preexisting conditions. (Ex.

A, pp. 9-10.) On June 4, 2019, this case was reassigned to my docket. (ECF Nos. 39-

40.)

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After the case was reassigned, petitioner filed a supplemental expert report from

Dr. Sheikh responding to Dr. Kedl’s first report and respondent then filed a further report

by Dr. Kedl. (ECF No. 41-42, 44; Exs. 51-67, C.) A Rule 5 conference was held on

December 4, 2019. (ECF No. 46.) With regard to Althen prong two, I observed that

petitioner was diagnosed by his treating neurologist with acute demyelinating

polyneuropathy/GBS. (Id. at 1 (citing Ex. 2, p. 278-79; Ex. 16, p. 564).) Preliminarily, I

indicated that I was not persuaded by Dr. Kedl’s opinions that petitioner’s symptoms

were more likely caused by peripheral neuropathy or, assuming petitioner did have

GBS, that his GBS was more likely caused by a subclinical infection. (Id. at 2.) Nor

was I persuaded by the lack of CSF or demyelination testing, given petitioner’s

response to IVIg and his physicians decision to forego further diagnostics. (Id. at 2-3.)

Dr. Kedl in his supplemental expert report had suggested that his and Dr. Sheikh’s

“differences of opinion boil down to whether one views the available data as an

immunologist or a neurologist.” (Ex. C, p. 1.) I indicated that respondent would likely

need to present an opinion by a neurologist if he wished to continue challenging

petitioner’s correct diagnosis and the logical sequence of cause and effect presented by

his clinical presentation. (ECF No. 46, p. 3.) Lastly, I noted that the main issue in this

case would most likely be focused on Althen prong one, the medical theory. (Id.) On

my preliminary review of the expert reports, I suggested that a hearing may be

necessary to fully explore the competing opinions. (Id.)

Following the Rule 5 conference, petitioner filed a second supplemental expert

report by Dr. Sheikh (ECF Nos. 51-52; Exs. 68-79) and additionally filed an expert

report from immunologist M. Eric Gershwin, M.D. (ECF Nos. 54-55; Ex. 80-94).

Respondent then responded by filing an expert report from neurologist Vinay Chaudhry,

M.D., and Dr. Kedl’s second supplemental expert report. (ECF Nos. 58-59; Exs. D-F.)

Dr. Chaudhry opined that petitioner’s diagnosed GBS “is lacking confirmatory support.”

(Ex. E, p. 20.) Petitioner then filed a further report by Dr. Gershwin. (ECF Nos. 62-65;

Exs. 96-128.) A two-day entitlement hearing was scheduled for January 10, 2023.

(ECF No. 68.) However, respondent later advised that his neurology expert, Dr.

Chaudhry, would not participate further in this case. (Non-PDF Scheduling Order, filed

May 4, 2021.) Respondent indicated that he intended to retain a different expert to

testify at the entitlement hearing. (Id.) On October 20, 2021, respondent filed an expert

report from neurologist Brian Callaghan, M.D., M.S. (ECF No. 73; Exs. G-H.) Dr.

Callaghan conceded for the first time on respondent’s behalf that petitioner likely

suffered GBS. (Ex. G, p. 4.)

On February 4, 2022, I issued a scheduling order informing the parties that a

ruling on entitlement by the undersigned involving GBS caused-in-fact by a Prevnar 13

vaccination was recently posted. (ECF No. 74.) I encouraged the parties to review my

ruling in Pierson, and to confer with their clients, experts, and each other. (Id.) I

ordered the parties to reassess their respective litigative risk and to consider whether

they would like to develop the record of this case further. (Id.) On March 7, 2022, the

parties filed a joint status report indicating that petitioner intended to further develop the

record of the case. (ECF No. 75.) Petitioner indicated that he retained a new

immunologist and intended to file an additional expert report. (Id.)

4

On March 14, 2022, a status conference was held wherein petitioner indicated

that he retained immunologist Lawrence Steinman, M.D., to testify in place of Dr.

Gershwin. (ECF No. 76.) Respondent requested the opportunity to file a responsive

supplemental expert report but otherwise raised no objection. (Id.) Subsequently,

petitioner and respondent filed supplemental expert reports from Drs. Steinman and

Kedl. (ECF No. 78, 81; Exs. 129-162, I.) A prehearing order was issued on October 11,

2022, setting the close of the record for November 29, 2022. (ECF No. 82.)

Subsequently, the entitlement hearing was rescheduled to commence on January 12,

2023, to accommodate respondent’s expert’s schedule. (Non-PDF Scheduling Order,

filed Oct. 11, 2022.) In the course of prehearing submissions, petitioner filed a

supplemental expert report by Dr. Steinman on November 29, 2022. (ECF No. 84; Exs.

163-177.) In response, respondent later filed medical literature marked as Exhibits J-L

and a demonstrative aid marked as Exhibit M. (ECF Nos. 100, 111.) However, the

hearing was ultimately continued to May 4, 2023. (ECF Nos. 114, 116.)

On March 14, 2023, petitioner filed a status report, indicating that his experts

were unavailable for the rescheduled entitlement hearing. (ECF No. 117.) “Due to the

age of this case, the age of Petitioner, and the previous enlargements of the hearing

dates requested by both sides,” petitioner requested to proceed with a motion for ruling

on the written record in lieu of an entitlement hearing. (Id.) During a follow up status

conference, respondent indicated that he did not object to proceeding on the written

record so long as he was provided an opportunity to file an expert report in response to

Dr. Steinman’s most recent report. (ECF No. 118.) Accordingly, the entitlement hearing

that was rescheduled for May 4, 2023, was cancelled. (Id.)

On April 18, 2023, petitioner filed a motion for ruling on the record pursuant to

Vaccine Rule 8(d). (ECF No. 119.) On June 20, 2023, respondent filed a supplemental

expert report by Dr. Kedl (ECF No. 122; Ex. N), and a response to petitioner’s motion

for ruling on the record (ECF No. 123). Petitioner filed his reply on September 6, 2023.

(ECF No. 126.)

In light of the above, I have determined that the parties have had a full and fair

opportunity to present their cases and that it is appropriate to resolve entitlement on the

existing record. See Vaccine Rule 8(d); Vaccine Rule 3(b)(2); see also Kreizenbeck ex

rel. C.J.K. v. Sec’y of Health & Human Servs., 945 F.3d 1362, 1366 (Fed. Cir. 2020)

(noting that “special masters must determine that the record is comprehensive and fully

developed before ruling on the record”). Accordingly, this matter is now ripe for

resolution.

III. Factual History

a. As reflected in the medical records

Petitioner was seventy-three years old when he received the Prevnar 13 vaccine

during a primary care appointment on July 13, 2016. (Ex. 1, p. 1.) Petitioner’s pre-

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vaccination history was significant for ischemic cardiomyopathy, coronary artery

disease, status-post coronary artery bypass graft and stent placement, congestive heart

failure, hypertension, paroxysmal atrial fibrillation, prostatic hypertrophy, chronic lower

extremity edema, diabetes mellitus, smoking, and obesity. (Ex. 2, pp. 2, 8, 195, 251,

275.) Petitioner presented to his cardiologist for a follow-up visit on July 25, 2016. (Id.

at 195.) He reported a few months of exertional dyspnea but no other new symptoms.

(Id. at 195-98.)

On August 5, 2016, petitioner presented to the emergency department with

complaints of acute back pain that had been waxing and waning for the past two days.

(Ex. 2, p. 274.) He also reported numbness and tingling in his hands and feet after

starting Crestor for better lipid control one week earlier. (Id.) He had a markedly

elevated blood pressure, for which he was treated. (Id. at 275-76.) Petitioner was

admitted to rule out acute coronary syndrome and dissecting aortic aneurysm. (Id. at

276.) Following admission, petitioner experienced chest pain and respiratory distress,

prompting his transfer from the medical floor to the intensive care unit. (Id. at 278.)

A CT scan of petitioner’s chest with contrast showed cardiomegaly and

pulmonary fibrotic changes with no acute process. (Ex. 2, pp. 217-18.) Petitioner’s

physical exam was normal except for IV/VI systolic murmur and 1-2+ edema in his lower

extremities. (Id. at 275.) His neurologic exam revealed no focal deficits. (Id.) The

assessment included hypertensive crisis, which was assumed to account for his

numbness, and unstable angina. (Id. at 276.) It was noted that his numbness and

tingling had resolved. (Id.)

Petitioner saw neurologist Steve Dofitas, M.D., on August 6, 2016, for weakness

and tingling in the extremities that began three days earlier. (Ex. 2, p. 278.) Petitioner

described progressing weakness in his upper and lower extremities and numbness that

extended from his lower extremities to his trunk. (Id.) He also reported numbness in his

tongue and difficulty with eating and swallowing that began the previous evening. (Id.)

The immunization history noted that petitioner “received immunization for flu and also

for pneumonia 2 weeks” earlier. 3 (Id.) On exam, petitioner exhibited 4/5 strength in all

extremities with the exception of 3/5 in his ankles. (Id. at 279.) He had sensory

impairment in his lower extremities up to the level of his umbilicus and to his elbows in

the upper extremities. (Id.) Deep tendon reflexes were absent throughout. (Id.) His

gait was not tested. (Id.) Dr. Dofitas’ impression was distal weakness and sensory

impairment with absent deep tendon reflexes and back pain. (Id.) Dr. Dofitas opined

that petitioner “likely has acute demyelinating polyneuropathy, the onset of which was

about 3 days ago.” (Id.)

Petitioner underwent a CT scan of his head, which was negative. (Ex. 2, p. 211.)

A cardiology progress note, dated August 6, 2016, noted that petitioner had developed

progressive numbness and weakness from his diaphragm and that a neurological

evaluation had been called for possible GBS. (Ex. 16, p. 608.) The report also noted

3

There is no record of a flu immunization, and petitioner does not allege in his petition that he received a

flu vaccine at the same time that he received the Prevnar 13 vaccine. (See Exs. 1, 95.)

6

that petitioner had “received [a] Pneumonia shot 2 weeks” earlier. (Id.) Petitioner was

started on IVIg and his weakness improved. (Id. at 519, 524.) He was transferred from

the intensive care unit to the medical floor on August 8, 2016, where he completed a

five-day course of IVIg. (Id. at 531, 561.) He still had difficulty ambulating, but his

sensation was slowly returning to normal. (Id. at 531.)

On August 11, 2016, petitioner was discharged to inpatient rehabilitation with the

following diagnoses: GBS, hematuria, hypertension, coronary artery disease, diabetes

mellitus, gastroesophageal reflux, hyperlipidemia, and thrombocytopenia. (Ex. 7, p. 8.)

At this point, petitioner required moderate assistance for sit to stand transfers and

maximum to moderate assistance for lower body dressing and bathing. (Id. at 20.)

Additionally, petitioner could only ambulate approximately three feet. (Id.) By August

31, 2016, petitioner’s ambulation had improved to 200 feet at a minimal assist level with

a rolling walker and stair navigation at a moderate assist. (Id.) It was noted that,

despite making functional gains, petitioner continued to struggle with stair navigation

and would likely require an ankle brace for mediolateral instability during his outpatient

rehabilitation. (Id.)

Following his stay at the hospital acute rehabilitation center, petitioner was

admitted to a subacute rehabilitation facility on September 1, 2016. (Ex. 5, p. 15.)

During his subacute rehabilitation, petitioner participated in physical therapy without any

specific complications. (Ex. 2, p. 291.) He was discharged from subacute rehabilitation

on September 16, 2016, with a diagnosis of, inter alia, unspecified demyelinating

disease of the central nervous system. (Id. at 290.) The discharge exam showed

significantly diminished grip strength and proximal lower extremity muscle weakness.

(Id. at 292.) Petitioner was able to stand for 5-6 minutes and was independent with self-

feeding and bathing using a tub bench, no further therapy was recommended. (Ex. 5, p.

35.) The discharge summary noted that he had developed lower extremity weakness 1-

2 weeks after receiving the Prevnar 13 vaccine. (Ex. 2, p. 291.)

Petitioner had an outpatient rehabilitation evaluation on September 21, 2016.

(Ex. 2, p. 202.) He was ambulating with a rolling walker but was unable to use the

stairs. (Id.) He had weakness in both legs, as well as numbness and tingling in his

legs, forearms, face, and back of his head. (Id.) His sensory exam was normal to light

touch, with diminished strength in the lower extremities and diminished deep tendon

reflexes bilaterally. (Id.) His gait was slow and abnormal. (Id. at 203.)

On September 29, 2016, petitioner saw his primary care physician, who noted his

recent GBS diagnosis. (Ex. 2, p. 204.) His urinary retention had resolved, but he had

continued weakness in his lower extremities and impaired sensation. (Id.)

Pneumococcal vaccine was listed as an allergy. (Id.)

Petitioner underwent an esophagram with barium on October 3, 2016, which

showed mild esophageal dysmotility. (Ex. 2, p. 207.) Petitioner returned to his primary

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care physician on October 11, 2016. (Ex. 7, p. 35.) He was taking Gabapentin 4 and

ambulating with an assistive device. (Id.) His exam showed 5/5 muscle strength in all

extremities and normal sensory, temperature, and pinprick testing in all extremities with

no gait ataxia. (Id. at 36.) His primary care physician assessed improving GBS. (Id. at

37.) Thereafter, petitioner self-discharged from skilled physical therapy on October 17,

2016, after eight sessions. (Ex. 11, p. 5.) He was happy with his progress and reported

less numbness and tingling, with the majority of his symptoms localized to his fingers

and hands. (Id.) He was still considered high risk for falls and using a quad cane to

navigate stairs and a rollator at home. (Id.)

On November 2, 2016, petitioner’s primary care physician noted that petitioner

“was given [a] Prevnar 13 injection in [his] office on July 13, 2016.” (Ex. 11, p. 7.)

“Approximately 3 weeks later[, petitioner] was admitted to Mercy Hospital from 8/5-

8/31/16 due to Guillain Barre Syndrome.” (Id.) He reported that his numbness in his

torso had subsided, but he continued to experience numbness and tingling in his hands,

legs, and face. (Id.) Although he described numbness in his bilateral lower extremities

that radiated from his thighs down, he stated that he had feeling in his feet and was

“more steady.” (Id.) Petitioner’s assessment included GBS and type 2 diabetes myelitis

with diabetic peripheral angiopathy. (Id. at 11.) At a follow up appointment on

December 13, 2016, petitioner continued to complain of weakness in his left leg due to

GBS. (Id. at 15.) He also complained of left knee pain with localized swelling that was

aggravated by descending the stairs. (Id.)

On January 18, 2017, petitioner returned to his primary care physician for an

annual exam. (Ex. 9, p. 6.) He was walking better, despite continued tingling in his legs

and feet and numbness in his lower legs and ankles. (Id.) He was also regaining

strength in his hands and fingers, despite continued tingling in his fingers. (Id.) He

reported a recent fall due to balance issues secondary to GBS and continued difficulty

navigating stairs. (Id. at 7.) On exam, it was noted that petitioner was obese but had

normal sensation to nylon filament to his feet for diabetic testing, normal grip strength,

and equal and symmetric deep tendon reflexes. (Id. at 8-9.) Petitioner was diagnosed

with GBS and advised to decrease his Gabapentin dosage “as he sees fit.” (Id. at 12.)

There was no mention of weakness or sensory impairment during a March 30,

2017, encounter with petitioner’s cardiologist. (Ex. 15, pp. 3-5.) He had a normal

cardiac exam, neurologic exam, and normal gait. (Id. at 4.) The assessment was

coronary artery disease. (Id.)

During an April 19, 2017, encounter with his primary care physician, petitioner

reported continued balance issues and difficulty getting up from squatting, sitting, and

laying. (Ex. 15, p. 7.) He noted that, although he was better, he was not back to

baseline. (Id.) He also reported a 10-day history of cold-like symptoms, including

4

Gabapentin is an orally administered anti-convulsant that is used treatment of partial seizures and in

management of postherpetic neuralgia. Gabapentin, DORLAND’S MEDICAL DICTIONARY ONLINE,

https://www.dorlandsonline.com/dorland/definition?id=19523&searchterm=gabapentin (last visited June 2,

2024).

8

cough, sinus pressure, eye pressure, and diarrhea, that were not responding to over-

the-counter cough medicine. (Id.) Petitioner’s assessment included GBS, and he was

directed that he could decrease or discontinue Gabapentin “as he sees fit.” (Id. at 11.)

On April 27, 2017, petitioner returned to his primary care physician with no specific

complaints. (Ex. 10, p. 4.) His primary care physician noted that the transient urinary

retention associated with petitioner’s GBS had resolved and that petitioner had a history

of incomplete bladder emptying, which was stable. (Id.) Petitioner denied incontinence.

(Id.)

On October 2, 2017, petitioner reported to his cardiologist that he was feeling

well and was able to garden and mow the lawn. (Ex. 15, p. 20.) His primary care

physician noted on October 31, 2017, that petitioner “developed Guillain Barre

syndrome from a Prevnar 13 immunization in July 2016.” (Id. at 29.) He was

developing flexion contractures in his right 3rd and 4th digits as well as left 2nd and 3rd

digits, which were attributed to GBS. (Id.) His HbA1C was 6.6 (normal reference range

4-6). (Id. at 33.) Petitioner was ordered to continue Gabapentin for his neuropathy.

(Id.)

IV. Summary of Expert Opinions and Qualifications

Each party presented opinions by three different experts, filing a total of fourteen

expert reports in support of their respective positions. Petitioner initially presented the

expert opinion of the neurologist, Kazim Sheikh, M.D. (Exs. 18, 51, 68, 106), and

immunologist, M. Eric Gershwin, M.D. (Exs. 80, 96). However, he later changed his

approach to the case and introduced new theories by neuroimmunologist, Lawrence

Steinman, M.D. (Exs. 129, 163.) Respondent initially presented the expert opinion of

immunologist, Ross M. Kedl, Ph.D. (Exs. A, C, D, I, N), and neurologist, Vinay

Chaudhry, M.D. (Ex. E.) However, Dr. Chaudhry was unable to continue the case and

respondent introduced the opinion of neurologist, Brian C. Callaghan, M.D. (Ex. G.)

In their briefs, the parties raised issues with specific experts’ qualifications to

opine on certain topics. (ECF No. 119, pp. 12-19; ECF No. 123, pp. 14-17; ECF No.

126, pp. 3-13.) Specifically, petitioner argued that Dr. Kedl, as a “non-medical expert,”

is not qualified to opine on the issue of diagnosis, specific causation, alternative cause,

or severity, and asserts that consideration of his opinion should be limited to general

causation. (ECF No. 119, p. 17.) Respondent argued that Dr. Sheikh, as a neurologist,

is not qualified to opine on a causal theory based on molecular mimicry, which is

immunological. (ECF No. 123, pp. 14-15.)

Because I have found for the reasons discussed under Althen prong one below

that the theory of molecular mimicry presented by Dr. Steinman with respect to

phosphoglycerol satisfies petitioner’s burden of proof, it is not necessary to reach the

other theories that were advanced. This includes Dr. Sheihk’s separate opinion

regarding molecular mimicry, in effect mooting respondent’s objection regarding Dr.

Sheikh’s qualifications. Additionally, respondent’s initial position based on the opinions

of Drs. Chaudhry and Kedl was that petitioner’s diagnosis of GBS was not established.

9

However, Dr. Callaghan subsequently agreed that petitioner was correctly diagnosed

with GBS. For the reasons discussed under Althen prong two below, I have found that

Dr. Callaghan’s clinical opinion obviated much of Dr. Kedl’s reasoning as to petitioner’s

own presentation. Those aspects of Dr. Kedl’s opinion that were noted under Althen

prong two were found not to affect the outcome based on the legal standards of the

Program. Accordingly, petitioner’s objection to Dr. Kedl’s qualifications is likewise moot.

Because Drs. Gershwin and Chaudhry were replaced as experts by Drs.

Steinman and Callaghan respectively, their opinions will not be summarized. I have,

however, considered their opinions and concluded that nothing in their opinions would

affect the outcome. Moriarty ex rel. Moriarty v. Sec’y of Health & Human Servs., 844

F.3d 1322, 1328 (Fed. Cir. 2016) (“We generally presume that a special master

considered the relevant record evidence even though he does not explicitly reference

such evidence in his decision.”); see also Paterek v. Sec’y of Health & Human Servs.,

527 F. App’x 875, 884 (Fed. Cir. 2013) (“Finding certain information not relevant does

not lead to—and likely undermines—the conclusion that it was not considered.”). Dr.

Gershwin’s two reports serve to elaborate on the molecular mimicry theory initially

presented by Dr. Sheikh, which it is not necessary to reach. Upon my review, nothing in

his broader discussion of GBS undermines Dr. Steinman’s subsequently presented

theory. Much of Dr. Chaudhry’s report was dedicated to challenging petitioner’s GBS

diagnosis; however, respondent subsequently abandoned that line of reasoning,

confirming in his response to petitioner’s motion for a ruling on the written record that he

is not disputing petitioner’s GBS diagnosis. (ECF No. 123, p. 14.) Although Dr.

Chaudhry did offer an opinion as to whether the Prevnar vaccine can cause GBS, he

confirmed in his report that he was deferring to Dr. Kedl with respect to the immunologic

details. (Ex. E, p. 15.) Moreover, Dr. Chaudhry exited the case before Dr. Steinman

presented the theory that is addressed under Althen prong one, below.

a. Petitioner’s Experts

i. Kazim Sheikh, M.D. 5

5

Dr. Sheik received his medical degree from King Edward Medical College in Lahore, Pakistan in 1987.

(Ex. 177, p. 1; Ex. 19, p. 1; Ex. 18, p. 1.) He completed an internship and residency at Mayo Hospital in

Lahore; an internship at Nassau County Medical Center in East Meadow, New York; a residency in

neurology at the Neurological Institute at Columbia University in New York, New York; and a postdoctoral

fellowship in peripheral nerve at Johns Hopkins University School of Medicine in Baltimore, Maryland.

(Ex. 177, p. 1.) Dr. Sheik is a board-certified psychiatrist and neurologist with special qualification in

muscle pathology, and he maintains his medical license in Texas. (Id. at 2; Ex. 18, p. 2.) He currently

works as a professor of neurology at the University of Texas Health Sciences, and as an attending

neurologist at Memorial Hermann Hospital and Lyndon B. Johnson Hospital all in Houston, Texas. (Ex.

177, p. 2.) Dr. Sheikh is a clinician-scientist with special training in neurology and peripheral nerve and a

longstanding interest in immune neuropathies, including the pathogenesis of GBS, in particular. (Ex. 18,

p. 1.) Since 2001, Dr. Sheikh has been continuously funded by the National Institutes of Health (“NIH”) to

study the pathogenesis of GBS, including three separate NIH grants that focused on understanding the

pathobiology of immune neuropathies. (Id.) He also has authored or co-authored more than 150

publications related to GBS and other inflammatory neuropathies. (Id.; Ex. 177, pp. 14-35.)

10

Petitioner filed four expert reports from Dr. Sheikh. (Exs. 18, 51, 68, 106.) Dr.

Sheikh opines that petitioner suffers from the acute inflammatory demyelinating

polyradiculopathy (“AIDP”) variant of GBS. (Ex. 18, p. 9.) He notes that petitioner

developed acute onset of numbness in his hands and feet, followed by severe back

pain, which was likely caused by inflammation in the spinal roots. (Id.) Dr. Sheikh

notes that petitioner’s initial diagnosis of aortic dissection was eventually ruled out. (Id.)

Petitioner then developed progressive distal and proximal weakness. (Id.) Dr. Sheikh

observes that the progression of sensory and motor symptoms was in an ascending

pattern. (Id.) Petitioner “also developed transient weakness of bulbar and respiratory

muscles as reflected by transient swallowing difficulties and respiratory distress and

reduced vital capacity, respectively.” (Id.) An exam performed by petitioner’s

neurologist on August 6, 2016, confirmed proximal and distal muscle weakness,

sensory impairment, and loss of deep tendon reflexes. (Id. (citing Ex. 2, p. 278).)

According to Dr. Sheikh, “[t]hese clinical features, including the distribution and

progression of sensory and motor symptoms, are consistent with an acute neuropathic

process.” (Id.) Moreover, his treating neurologist opined that petitioner has the AIDP

form of GBS. (Id.) Although, this was not confirmed by nerve conduction studies, Dr.

Sheikh explains that the quick response to IVIg and subsequent course of recovery in a

73-year-old patient are consistent with AIDP. (Id.; Ex. 106, p. 1.) He opines that the

treating physicians’ decision not to perform a spinal tap and/or nerve conduction study

was reasonable, “given the quick treatment response and the monophasic course of the

illness.” 6 (Ex. 18, p. 9.) Additionally, Dr. Sheikh suggests “the results of these studies

would not have altered petitioner’s management after the recovery started.” (Id.; Ex. 68,

p. 4.)

Dr. Sheikh notes that there was no evidence of preceding infection in petitioner’s

case. (Ex. 51, p. 3.) A careful look at the serial CBC studies, followed by admission

CBC on August 5, 2016, showed WBC within normal range; and Dr. Sheikh notes that

neutrophils were 78 (normal 50-75) and subsequent CBC studies showed either

elevated or normal neutrophil counts with elevated WBC peaking on August 9, 2016 to

>19 (normal 4-11). (Id. (citing Ex. 16, pp. 664-65).) These blood counts, he stresses,

were performed after the onset of petitioner’s neurologic symptoms and cannot be

considered as a reflection of an antecedent event or infection. (Id.) Moreover, no

infection was established throughout extensive work up during petitioner’s hospital

admission. (Id.) GBS patients that suffer from preceding infection typically have

preceding symptoms, including fever, cough, sore throat, nasal discharge, or symptoms

6

Dr. Sheikh opines that petitioner meets the Brighton clinical criteria and has level 3 certainty for GBS.

(Ex. 106, pp. 2-3.) The Brighton Criteria set forth diagnostic criteria that provide different levels of

certainty for the standardization of case definitions to improve vaccine safety. (Id. at 2 (citing 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) (Ex. 108)).)

A significant limitation of this criteria is that GBS follows a monophasic course that becomes evident after

follow-up, which can limit its use in clinical diagnosis at the time of presentation. (Id.) The criteria,

however, has several levels of confidence based on the availability of spinal fluid and EMG testing. (Id.)

In petitioner’s case, he demonstrated bilateral and flaccid weakness of the limbs; decreased or absent

deep tendon reflexes in weak limbs; and a monophasic illness pattern with interval onset and nadir of

weakness between 12 hours and 28 days, followed by subsequent clinical plateau. (Id.)

11

indicative of a gastrointestinal illness (diarrhea, abdominal pain, and vomiting). (Id.

(citing M. Koga et al., Antecedent Symptoms in Guillain-Barré Syndrome: An Important

Indicator for Clinical and Serological Subgroups, 103 ACTA NEUROLOGICA SCANDINAVICA

278, 281 (2001) (Ex. A, Tab 14, p. 4) (reporting “[p]receding symptoms were reported in

154 (88%) of the 176 patients”)).) Dr. Sheikh notes that petitioner did not complain of

any of the common preceding symptoms reported by Koga et al. (Id.)

Furthermore, Dr. Sheikh opines petitioner did not suffer from hypertensive

encephalopathy. (Ex. 106, p. 4.) “The focal neurological deficits in hypertensive

emergencies are due to ischemia of the brain, including ischemic or hemorrhagic

strokes,” and Dr. Sheikh notes that they “do not have an ascending pattern.” (Id.)

“[T]ypical hypertensive encephalopathy features include ‘agitation, delirium, stupor,

seizures or visual disturbances,’” none of which petitioner had. (Id.) Petitioner

presented with symmetric sensory and motor features on both sides, therefore, in order

to implicate hypertensive urgency or encephalopathy, there would have to be insult to a

substantial proportion of the brain or brainstem to be ischemic. (Id.) That level of

ischemic insult to the brain or brainstem “would be incompatible with clinically normal

attention, consciousness/alertness, cognition, speech and language functions, cranial

nerves and absence of other central signals.” (Id.) Given that petitioner’s chest CT did

not show acute pulmonary edema or new intrinsic disease (Ex. 2, pp. 217-18), Dr.

Sheikh stresses that cardiac disease, i.e., heart failure causing petitioner’s shortness of

breath, is not supported. (Id. at 2.) Dr. Sheikh notes that petitioner was treated with

IVIg, a treatment that could potentially aggravate heart failure rather than improve it.

(Id.) Although petitioner did not require mechanical ventilation, Dr. Sheikh explains that

respiratory weakness, like weakness in the limb muscles, can vary in terms of severity

and “only patients with severe respiratory muscle weakness with severely reduced vital

capacity require mechanical ventilation.” (Id.)

Dr. Sheikh recognizes that the precise mechanisms for the development of GBS

are not completely understood. (Ex. 68, p. 3.) He explains that the general

understanding is that GBS is “triggered by environmental agents in genetically

susceptible hosts.” (Id.; Ex. 18, pp. 4-5.) Dr. Sheikh explains that activation of the

innate immune system is necessary to break self-tolerance and induce autoimmunity

and that stimulation of the immune system via vaccination can disrupt the balance

needed to maintain immunologic homeostasis, triggering host susceptibility to

autoimmune disease. (Ex. 18, p. 5 (citing Hanspeter Waldner et al., Activation of

Antigen-Presenting Cells by Microbial Products Breaks Self Tolerance and Induces

Autoimmune Disease, 113 J. CLINICAL INVESTIGATION 990 (2004) (Ex. 30)).) However,

the genes that impart host susceptibility to developing GBS are not firmly established,

and the pathogenesis of AIDP, in particular, is not well defined. (Ex. 68, pp. 1, 3.)

Dr. Sheikh maintains the concept of molecular mimicry is the most accepted

pathogenic mechanism for GBS, particularly for it its axonal variant. (Ex. 18, pp. 4, 7

(citing K. A. Sheikh et al., Molecular Mimicry in Guillain-Barré Syndrome, 845 ANNALS

N.Y. ACAD. SCIS. 307 (1998) (Ex. 22); Hugh J. Willison, The Immunology of Guillain-

Barré Syndromes, 10 J. PERIPHERAL NERVOUS SYSTEM 94 (2005) (Ex. 23)).) The

12

strongest evidence in this regard comes from studies of axonal GBS patients that follow

Campylobacter jejuni (“C. jejuni”) infection. (Id. at 7.) For example, “[Campylobacter]

bacteria carries carbohydrate moieties that mimic peripheral nerve glycolipids called

gangliosides, and patients with post-[Campylobacter] axonal GBS commonly have anti-

ganglioside antibodies.” (Id.) “Experimental studies demonstrate that the anti-

ganglioside antibodies can produce inflammatory nerve injury mimicking axonal GBS in

experimental models.” (Id. (citing Jaap J. Plomp et al., Miller Fisher Anti-GQ1b

Antibodies: α-Latrotoxin-Like Effects on Motor End Plates, 45 ANNALS NEUROLOGY 189

(1999) (Ex. 40); Lan He et al., Anti-Ganglioside Antibodies Induce Nodal and Axonal

Injury Via Fcγ Receptor-Mediated Inflammation, 35 J. NEUROSCI. 6770 (2015) (Ex. 41)).)

In petitioner’s case, Dr. Sheikh proposes two theories of molecular mimicry: (1) a

structural mimic between the carbohydrates in the Prevnar 13 vaccine and a major

glycolipid in the myelin sheath, and (2) a sequential mimic between myelin protein P0

and the diphtheria toxoid protein conjugate portion of the Prevnar 13 vaccine

(CRM197). (Id. at 7-8; Ex. 68, pp. 2-3.) However, because I have accepted Dr.

Steinman’s separately presented theory of molecular mimicry as discussed below, it is

not necessary to further address the specific molecular mimics proposed by Dr. Sheikh.

Dr. Sheikh also proposes several additional, alternative theories for how the Prevnar 13

vaccine could cause GBS. (Ex. 18, p. 8; Ex. 51, p. 4.) Again, however, it is not

necessary to address these further in light of Dr. Steinman’s additional opinion.

Finally, Dr. Sheikh opines that petitioner’s onset approximately three weeks post-

vaccination is medically acceptable, given the lag period for post-vaccination

autoimmune complications. (Ex. 18, p. 9.) He explains that inciting events, such as

vaccination, are considered biologically relevant if onset of neurologic symptoms occurs

within 6 weeks of the inciting event. (Ex. 51, p. 2.)

ii. Lawrence Steinman, M.D. 7

Petitioner filed two expert reports from Dr. Steinman. (Exs. 129, 163.) At the

outset, Dr. Steinman notes that the theory that he proposes in this case is congruent

with the theories he has provided in prior cases, in which he provided expert testimony

on behalf of petitioners alleging that their GBS was caused-in-fact by the Prevnar 13

vaccine. (Ex. 129, p. 4.)

Dr. Steinman proposes two theories of molecular mimicry: (1) a structural

phospholipid-based mimic, centered on the phosphoglycerol component common to

phosphatidyl-ethanolamine, phosphatidyl-choline, and phosphatidylserine and (2) a

sequential mimic between CRM197 (a protein component used to conjugate the

7

Dr. Steinman received his medical degree and completed an NIH fellowship in chemical neurobiology at

Harvard University, before moving on to Stanford University Hospital where he completed an internship in

surgery, a residency in pediatrics, and a residency in pediatric and adult neurology. (Ex. 130, p. 1.) He is

board certified in neurology. (Id. at 2.) He currently works a professor in the Departments of Neurology

and Neurological Sciences, and Pediatrics and Genetics at Stanford University where his “research

centers on how the nervous system is attacked by the immune system." (Id. at 1; Ex. 129, p. 3.) He has

published nearly 600 articles, including 11 articles concerning molecular mimicry in which Dr. Steinman is

the first author. (Ex. 130, pp. 5-48; Ex. 129, p. 1.)

13

pneumococcal polysaccharides in the Prevnar 13 vaccine) and an immunogenic protein

carrier known as Contactin-1. (Ex. 129, pp. 6-26.) Dr. Steinman’s first theory begins

with the premise that antibodies to phospholipids are seen in GBS. (Id. at 7 (citing B.

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

Guillain-Barre Syndrome: Cross-Reactive or Pathogenic?, 16 AUTOIMMUNITY 23 (1993)

(Ex. 141)).) Citing his own research, Dr. Steinman explains that phospholipids are

components of myelin sheath that are targeted by antibodies in neuroinflammation. (Id.

(citing Jennifer L. Kanter et al., Lipid Microarrays Identify Key Mediators of Autoimmune

Brain Inflammation, 12 NATURE MED. 138 (2006) (Ex. 135); Peggy Ho et al.,

Identification of Naturally Occurring Fatty Acids of the Myelin Sheath that Resolve

Neuroinflammation, SCI. TRANSLAT’L MED. June 6, 2012, (Ex. 136)).) In the study by Ho

et al., Steinman and his colleagues demonstrated that “[l]ipids constitute 70% of the

myelin sheath, and autoantibodies against lipids may contribute to the demyelination

that characterizes multiple sclerosis.” (Id. (quoting Ho et al., supra, at Ex. 136, p. 1).)

The group used lipid antigen microarrays and lipid mass spectrometry to identify lipid

targets of the autoimmune response in a multiple sclerosis (“MS”) brain and in an

animal model of MS. (Id. (citing Ho et al., supra, at Ex. 136, p. 1).) Ho et al., “found that

autoantibodies in MS target a phosphate group in phosphatidylserine and oxidized

phosphatidylcholine derivatives.” (Id. (citing Ho et al., supra, at Ex. 136, p. 1).) The

main target of the human immune response to the myelin lipids was the

phosphoglycerol component. (Id. (citing Ho et al., supra, at Ex. 136, p. 1).)

Prior to the study by Ho et al., Gilburd et al. published results demonstrating that

6 out of 16 GBS sera had autoantibodies to one or more of the antigens studied, which

included phosphatidyl-ethanolamine, phosphatidyl-choline, and phosphatidylserine.

(Ex. 129, pp. 7-8 (citing Gilburd et al., supra, at Ex. 141).) The Gilburd study did not

identify these molecules as the cause of GBS. (Id. at 8 (citing Gilburd et al., supra, at

Ex. 141).) Instead, the authors concluded, “We believe that the autoantibodies found in

6 of the 16 GBS patients [were] produced as a result of the myelin damage, rather than

the cause of the inflammatory demyelination.” (Id. (quoting Gilburd et al., supra, at Ex.

141, p. 6).) Dr. Steinman counters this conclusion and explains that, “[a]s so often

happens as science progresses, in light of later findings . . . their ‘belief’ can be re-

interpreted based on the body of scientific evidence that emerged after their study.”

(Id.) Dr. Steinman suggests the Gilburd et al. study’s observations were accurate, “but

their ‘beliefs’ might undergo revision.” (Id.) Subsequently, Nakos et al. found

phospholipid antibodies were in GBS patients. (Id. (citing G. Nakos et al., Anti-

Phospholipid Antibodies in Serum from Patients with Guillain-Barré Syndrome, 31

INTENSIVE CARE MED. 1401 (2005) (Ex. 142)).) In that study, four blood serum samples

were obtained before and after treatment with γ-globulin. (Id. (quoting Nakos et al.,

supra, at Ex. 142, p. 1).) Researchers found that anti-phospholipid antibodies of the

IgM, IgA, and IgG families were detected in the sera of all GBS patients studied and

none of the controls. (Id. (quoting Nakos et al., supra, at Ex. 142, p. 1).)

Phosphatidylinositol, cardiolipin, phosphatidylcholine, and phosphatidic acid were the

main antigens. (Id. (quoting Nakos et al., supra, at Ex. 142, p. 1).)

14

Dr. Steinman explains that phosphatidylserine is a glycerophospholipid that

“consists of two fatty acids attached in ester linkage to the first and second carbon of

glycerol and serine attached through a phosphodiester linkage to the third carbon of the

glycerol.” (Ex. 129, p. 8 (citing Nakos et al., supra, at Ex. 142).) “The glycerophosphate

is on the third carbon in the glycerol bridge.” (Id.) Citing Chang et al., Dr. Steinman

indicates that the phosphoglycerol linkage is necessary “for immunogenicity of these

capsular polysaccharides.” (Id. at 9 (citing Janoi Chang et al., Relevance of O-Acetyl

and Phosphoglycerol Groups for the Antigenicity of Streptococcus Pneumoniae

Serotype 18C Capsular Polysaccharide, 30 VACCINE 7090 (2012) (Ex. 143)).) Chang et

al. identified a complex structure in the repeating unit of serotype 18C in the Prevnar 13

vaccine, which has “a branched pentasaccharide with two apparently labile substituents:

glycerol-phosphate and O-acetyl group.” (Id. (quoting Chang et al., supra, at Ex. 143, p.

1.) The authors concluded that “[t]he loss of these groups may potentially reduce the

ability of the 18C polysaccharide to induce the desired immune response.” (Id. (quoting

Chang et al., supra, at Ex. 143, p. 1).) Dr. Steinman concludes the phosphate head

group on glycerophosphate is critical for the immunogenicity of the 18C component of

Prevnar 13. (Id. at 10.) Dr. Steinman draws further support from the Prevnar 13 patent,

which mentions glycerophosphate “in the embodiment of the invention.” (Id. at 11.)

In addition to the Chang et al. paper emphasizing the need for phosphoglycerol

in the immunogenicity of 18C, Dr. Steinman cites the work of Bryson et al., which

demonstrates the human antibody response to CPS 23F. (Ex. 129, pp. 11-13 (citing

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) (Ex.

146)).) Bryson et al. studied two antibodies directed to 23F from humans who were

immunized with Pneumovax 23. 8 (Id. at 11-12 (citing Bryson et al., supra, at Ex. 146).)

According to Dr. Steinman, the Bryson et al. study shows that phosphoglycerol is

directly targeted by the core of the two human antibodies targeting 23F and that the

phosphoglycerol in the polysaccharide capsule of serotype 23F is critical to the human

immune response to serotype 23F. (Id. at 11-15 (citing Bryson et al., supra, at Ex.

146).) Dr. Steinman asserts that, because the 23F and 18C components of Prevnar 13

also contain the phosphoglycerol moiety that is targeted by the antibodies generated by

Pneumovax 23, it is very likely that the immune response to the 23F and 18C

components of Prevnar 13 also target the phosphoglycerol moiety. (Id. at 15 (citing

Prevnar 13 Prescribing Information [hereinafter Prevnar 13 Package Insert], Ex. 140;

Chang et al., supra, at Ex. 143).) He concludes, “[i]n my opinion, this is exceptionally

‘close’ to what I think would constitute ‘certainty’ on the question of whether humans

who receive a pneumococcal vaccine make antibodies that target phosphoglycerol.”

(Id. at 16.)

8

Although Dr. Steinman acknowledges that the Bryson study was performed with Pneumovax 23, he

explains that, like the Prevnar 13 vaccine, the Pneumovax 23 vaccine contains the 18C and the 23F. (Ex.

129, pp. 12-13 (citing Bryson et al., supra, at Ex. 146).) Because a study has not yet been conducted

using the Prevnar 13 vaccine, Dr. Steinman asserts that the Bryson et al. study “is the best the Petitioner

can do at the present time.” (Id. at 13 (citing Bryson et al., supra, at Ex. 146).)

15

The second area of molecular mimicry Dr. Steinman identifies occurs between

CRM197 and an immunogenic protein carrier known as Contactin-1. (Ex. 129, p. 16.)

Dr. Steinman explains that Contactin-1 is “targeted in some cases of GBS.” (Id. (citing

Yumako Miura et al., Contactin I IgG4 Associates to Chronic Inflammatory

Demyelinating Polyneuropathy with Sensory Ataxia, 138 BRAIN 1484 (2015) (Ex. 150)).)

In order to test the components of the Prevnar 13 vaccine, Dr. Steinman conducted

BLAST searches 9 to align Contactin-1 with the components of CRM197 in the Prevnar

13 vaccine. (Id.) Dr. Steinman then submitted his BLAST results in the Immune

Epitope Database (IEDB) 10 to determine whether other researchers have identified the

epitope(s). (Id. at 22.) Dr. Steinman first tested the sequence WEQAKALSVE and

determined that this sequence is both found on human immune cells and an epitope in

diphtheria toxin, which has only one amino acid difference from CRM197. (Id. at 23.)

Dr. Steinman tested a second sequence, EYMAQACAGNRVRR, which also has “known

cross-reactivity with epitopes described in humans and on the c. diphtheria microbe that

is the basis for CRM197.” (Id. at 25 (citing Raghavanpillai Raju et al., Epitopes for

Human CD4+ Cells on Diphtheria Toxin: Structural Features of Sequence Segments

Forming Epitopes Recognized by Most Subjects, 25 EUR. J. IMMUNOLOGY 3207 (1995)

(Ex. 159)).) These results, Dr. Steinman explains, demonstrate a compelling theory that

molecular mimics in the Prevnar 13 vaccine, received by petitioner, “could trigger

inflammatory neuropathy culminating in GBS.” (Id. at 26.)

Dr. Steinman cites two case reports discussing the association of Prevnar 13

vaccination and GBS. (Ex. 129, p. 27.) The first report was of “a woman who

developed bilateral lower extremity weakness from [GBS] a month after administration

9

According to the NIH website, the Basic Local Alignment Search Tool (BLAST) “finds regions of local

similarity between sequences” and “can be used to infer functional and evolutionary relationships

between sequences as well as help identify members of gene families.” Basic Local Alignment Search

Tool, NAT’L LIBR. MED., https://blast.ncbi.nlm.nih.gov/Blast.cgi (last visited July 17, 2024). Dr. Steinman

classifies his criteria for a molecular mimic as a run of at least 5 out of 12 amino acids that are identical.

(Ex. 129, p. 16.) Based on his own published research, Dr. Steinman opines that the identity of 5 of 12

amino acids were sufficient to “trigger clinically relevant neuroinflammation with paralysis.” (Id. (citing

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

Autoimmune Encephalomyelitis, 127 J. EXPERIMENTAL MED. 605 (1992) (Ex. 151); Anand Gautam et al.,

Minimum Structural Requirements for Peptide Presentation by Major Histocompatibility Complex Class II

Molecules: Implications in Induction of Autoimmunity, 91 PROC. NAT’L ACAD. SCIS. USA 767 (1994) (Ex.

152); Anand 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) (Ex. 153); Tobias V.

Lanz et al., Clonally Expanded B Cells in Multiple Sclerosis Bind EBV EBNA1 and GlialCAM, 603 NATURE

321 (2022) (Ex. 154); William H. Robinson & Lawrence Steinman, Epstein-Barr Virus and Multiple

Sclerosis, 375 SCIENCE 264 (2022) (Ex. 155); Kjetil Bjornevik et al., Longitudinal Analysis Reveals High

Prevalence of Epstein-Barr Virus Associated with Multiple Sclerosis, 375 SCIENCE 296 (2022) (Ex. 156);

Hartmut Wekerle, Multiple sclerosis Sparked by Virus-Led Autoimmunity, 603 NATURE 230 (2022) (Ex.

157)).) He also adds that the 5 out of 12 identical amino acids need not be consecutive. (Id.)

10

The IEDB “catalogs experimental data on antibody and T cell epitopes studied in humans, non-human

primates, and other animal species in the context of infectious disease, allergy, autoimmunity, and

transplantation. The IEDB also hosts tools to assist in the prediction and analysis of epitopes.” (Ex. 129,

pp. 22-23 (citing IMMUNE EPITOPE DATABASE & TOOLS, https://www.iedb.org/home_v3.php (last visited July

17, 2024).)

16

of the PCV”—also cited by Dr. Sheikh. (Id. (citing Nidhi Ravishankar, Guillain-Barre

Syndrome Following PCV Vaccine, 2 CLINICS SURGERY 1413 (2017) (Ex. 160)).) The

second report was published in October 2016 by the CDC and describes eleven reports

of GBS following Prevnar 13 vaccination. (Id. (citing 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) (Ex.

161)).) The median time range was nine days following vaccination; and the median

age was sixty-eight years old. (Id.) The article reports only one individual had an upper

respiratory infection sixteen days prior to GBS. (Id.)

In this case, Dr. Steinman observes that petitioner presented to his primary care

provider at Southtowns Family Practice for a “Welcome to Medicare” visit on July 13,

2016, during which, the vaccination at issue in this case was administered. (Ex. 129, p.

27 (citing Ex. 2, p. 81, 85).) “On August 5, 2016, approximately three weeks later,

[petitioner] presented to Mercy Hospital with acute upper back pain that had been

continuing for two days.” (Id. (citing Ex. 2, p. 274).) “At that time, he also complained of

numbness in his hands and feet.” (Id.) Dr. Steinman concludes the onset was in a time

interval of approximately 3 weeks. (Id.) He agrees with Dr. Sheikh’s opinion that

petitioner’s three-week onset was medically acceptable and consistent with the timing

supported by Schonberger et al., an epidemiologic study concerning the 1976 swine flu

vaccine and GBS, which he explains is often used as a “surrogate” in post-vaccination

GBS cases. (Id. (citing Lawrence Schonberger et al., Guillain-Barre Syndrome

Following Vaccination in the National Influenza Immunization Program, United States,

1976-1977, 110 AM. J. EPIDEMIOLOGY 105 (1979) (Ex. 162)).)

Responding to a critique by Dr. Kedl suggesting that phosphoglycerol is

widespread in the body, Dr. Steinman’s second report provides examples wherein

certain “targets,” or epitopes, are expressed in multiple tissues throughout the body, but

still result in autoimmune disease without causing dysfunction at all other locations of

antigen expression. (Ex. 163, pp. 4-5.) He explains that Aquaporin 4 (AQP4) is the

target antigen in neuromyelitis optica (NMO); and AQP4 is expressed in the kidney, as

well as in astrocytes lining the brain and within the brain and optic nerve itself. (Id.)

Yet, patients with NMO do not also suffer renal disease, although AQP4 is expressed in

the kidney. (Id.) He also points to the relationship between gangliosides and C. jejuni,

noting that “an immune response to gangliosides found in [C. jejuni] only leads to GBS,”

despite the presence of gangliosides throughout the body. (Id. at 10.) Following this

logic, Dr. Steinman suggests that the fact that phosphoglycerol is a widespread antigen

would not discount the idea that it can induce an organ specific disease. (Id. at 4-5, 10,

19.)

Turning to Dr. Kedl’s critique of the Nakos et al. article, Dr. Steinman stresses

that data regarding IgG antibody levels in the article was listed as “data not shown.”

(Ex. 163, p. 7 (quoting Nakos et al., supra, at Ex. 142).) He suggests a transient

increase in antibodies to phospholipids detected by the study could have been

secondary to the process of responding to IVIg, and not due to contamination with anti-

17

phospholipid antibody in the IVIg preparation. (Id. at 7-8.) Moreover, not all patients

who are administered IVIg for GBS respond, and not all patients who respond to the

treatment respond immediately. (Id. at 8.) However, because the data is not shown, he

suggests that the Nakos et al. article does “not tell us whether treatment with IVIg

causing a transient rise in antibodies to phospholipids led to detrimental effects,” and in

fact, another study supports the safety of treating anti-phospholipid syndrome patients

with IVIg. (Id. (citing Y. Sherer et al., Antiphospholipid Antibody Levels in Intravenous

Immunoglobulin (IVIg) Preparations, 10 LUPUS 568 (2001) (Ex. 173)).) Additionally, Dr.

Steinman asserts that the adjuvanticity of alum, an adjuvant contained in the Prevnar 13

vaccine, “might heighten an anti-phospholipid immune response.” (Id.) Dr. Steinman

also defends his interpretation of the data from the Gilburd et al. study, explaining that

the authors “had no way of knowing later research from Nakos, Chang, Bryson and the

inventions in issued US patents concerning the key role of phosphoglycerol in the

immune response to Prevnar 13 vaccine[.]” (Id. at 10 (citing Gilburd et al., supra, at Ex.

141; Nakos et al., supra, at Ex. 142; Chang et al., supra, at Ex. 143; Bryson et al.,

supra, at Ex. 146).)

b. Respondent’s Experts

i. Ross M. Kedl, Ph.D. 11

Respondent filed five expert reports from Dr. Kedl. (Exs. A, C, D, I, N.) Dr. Kedl

opines that petitioner’s GBS was more likely caused by his “coincident and consistent

litany . . . of pre-vaccination medical maladies.” (Ex. A, p. 9.) He notes that petitioner’s

pre-vaccination medical history was significant for obesity, hypertension, diabetes

mellitus, hyperlipidemia, coronary artery disease, ischemic cardiomyopathy and

congestive heart failure, paroxysmal atrial fibrillation, prostatic hypertrophy, venous

insufficiency, peripheral vascular disease, GERD, and Vitamin B12 deficiency. (Id.)

According to Dr. Kedl, “all of these conditions are indicative of a highly elevated

inflammatory internal environment predisposing [petitioner] to a variety of pathologies.”

(Id.) He stresses “the inflammatory nature of adipose tissue . . . and its association with

both type II diabetes and peripheral neuropathies.” (Id. (citing Shannon M. Reilly & Alan

11

Dr. Kedl received his Ph.D. in pathobiology from the University of Minnesota Medical School in 1997,

before going on to complete a postdoctoral fellowship at the Howard Hughes Medical Institute in 2001.

(Ex. B, p. 1.) After completing his postdoctoral fellowship, Dr. Kedl worked as a senior immunologist in

the Immune Response Modifier program at 3M Pharmaceuticals. (Id. at 2; Ex. A, pp. 1-2.) In that

capacity, his work focused on “the design, development, and mechanisms of action of small TLR7/8

agonists.” (Ex. A, p. 2.) He currently works as a professor in the Department of Immunology and

Microbiology at the University of Colorado. (Id. at 1; Ex. B, p. 2.) Since joining the faculty at the

University of Colorado in 2004, Dr. Kedl has maintained an NIH funded research program that has

focused on “the biology of vaccine adjuvants and their capacity to induce robust and enduring cellular

immunity.” (Ex. A, p. 1; Ex. B, pp. 10-11.) He has also participated in NIH funded projects concerning

“the study of antigen inexperienced T cell subsets as well as . . . the role of lymphatic endothelial cells in

the management of T cell memory after vaccination or viral challenge.” (Ex. A, p. 1.) Dr. Kedl has

published over 65 peer-reviewed articles, 2 book chapters, and 13 invited reviews and commentaries.

(Ex. B, pp. 11-17.) He has “more than 20 years of experience (incorporating both academic and industry

perspectives) in evaluating the influence of vaccine adjuvants on the induction of local and systemic

inflammation and its eventual induction of downstream adaptive immunity.” (Ex. A, p. 2.)

18

R. Saltiel, Adapting to Obesity with Adipose Tissue Inflammation, 13 NATURE REVS.:

ENDOCRINOLOGY 633 (2017) (Ex. A, Tab 22); Rens Hanewinckel et al., The

Epidemiology and Risk Factors of Chronic Polyneuropathy, 31 EUR. J. EPIDEMIOLOGY 5

(2016) (Ex. A, Tab 9)).) Moreover, obesity alters the microbiota in the host and

increases susceptibility to infection with C. jejuni infection. (Id. (citing S. Bereswill et al.,

What You Eat Is What You Get: Novel Campylobacter Models in the Quadrangle

Relationship Between Nutrition, Obesity, Microbiota, and Susceptibility to Infection, 1

EUR. J. MICROBIOLOGY & IMMUNOLOGY 237 (2011) (Ex. A, Tab 2)).) Commensurate with

the development of symptoms and suspected diagnosis of GBS, Dr. Kedl notes that

petitioner had repeated demonstrations of elevated white blood cell count / neutrophilia

and dysregulated blood chemistry. (Id. (citing Ex. 16, pp. 663-65).) “This is indicative of

a concomitant subclinical infection that [petitioner’s] physicians or expert failed to

notice[,]” which Dr. Kedl explains is not unusual because only a minority of patients

experience symptoms in response to the infections commonly associated with GBS.

(Id. (citing Koga et al., supra, at Ex. A, Tab 14); Ex. C, p. 4.) Moreover, he suggests

that petitioner’s elevated neutrophil count during the course of IVIg treatment is further

evidence of an ongoing infection because IVIg treatment typically results in a decrease

in neutrophil count within a few days after treatment initiation. (Id.) Because GBS is

frequently preceded by infection, Dr. Kedl concludes that infection is a far more likely

cause of petitioner’s neurological complications. (Id. at 10.)

Dr. Kedl opines that “molecular mimicry is questionable as a relevant mechanism

of neuronal injury.” (Ex. A, p. 4.) He notes that Dr. Sheikh relies on data demonstrating

a relationship between post-infectious (not post-vaccination) anti-gangliosides. (Ex. C,

p. 5.) Moreover, Dr. Kedl stresses that the causal relationship between ganglioside-

specific antibodies and GBS is poorly linked as it is found in only a small minority (20-

30%) of GBS patients. (Ex. A, p. 5 (citing Maksimiljan Gorenjac, Clinical and Diagnostic

Role of Ganglioside Antibody Testing, 15 J. INT’L FED’N CLINICAL CHEMISTRY & LAB’Y MED.

95 (2004) (Ex. A, Tab 6); Koga et al., supra, at Ex. A, Tab 14); see also Adi Hersalis

Eldar & Joab Chapman, Guillain Barré Syndrome and Other Immune Mediated

Neuropathies: Diagnosis and Classification, 13 AUTOIMMUNITY REVS. 525, 526 (2014)

(Ex. A, Tab 5, p. 2) (noting “the majority of GBS patients (AIDP subtype) have no

identified autoantibodies so the pathogenesis of the disease is still debated.”).)

Moreover, Dr. Kedl maintains that reports of experimentally induced ganglioside specific

antibody mediated pathology (as a result of ganglioside immunization) are “misleading

and contradictory.” (Ex. A, p. 5.) He takes issue with the fact that these studies are

performed with repeated immunizations of large amounts of gangliosides emulsified in

heat killed mycobacteria and mineral oil, i.e., Complete Freund’s Adjuvant, which is

highly inflammatory. (Id. (citing Tyrone Bowes et al., Tolerance to Self Gangliosides is

the Major Factor Restricting the Antibody Response to Lipopolysaccharide Core

Oligosaccharides in Campylobacter jejuni Strains Associated with Guillain-Barré

Syndrome, 70 INFECTION & IMMUNITY 5008 (2002) (Ex. A, Tab 3); A.L. Moyano et al.,

Validation of a Rabbit Model of Neuropathy Induced by Immunization with Gangliosides,

272 J. NEUROLOGICAL SCIS. 110 (2008) (Ex. A, Tab 21); Nobuhiro Yuki et al.,

Carbohydrate Mimicry Between Human Ganglioside GM1 and Campylobacter jejuni

Lipooligosaccharide Causes Guillain-Barré Syndrome, 101 PROC. NAT’L ACAD. SCIS.

19

11404 (2004) (Ex. A, Tab 27)); Ex. C, pp. 6-7.) Additionally, Dr. Kedl emphasizes that

the “outrageously toxic mixture” used to induce GBS-like symptoms in the animal

models cited by Dr. Sheikh cannot be used to interpret what a clinical vaccine

preparation may or may not do simply because both happen to be injected. (Ex. C, p.

7.) He further notes that, even when utilizing this “overwhelmingly inflammatory

formulation,” studies have still found induction of GBS-like symptoms to be variable or

nonexistent. (Ex. A, p. 5 (citing Somsankar Dasgupta et al., Lack of Apparent

Neurological Abnormalities in Rabbits Sensitized by Gangliosides, 29 NEUROCHEMICAL

RSCH 2147 (2004) (Ex. A, Tab 4)).)

Dr. Kedl stresses that “antibodies against self-antigens can be found in all

healthy individuals.” (Ex. A, p. 6 (citing Vincent Hurez et al., Expression and Control of

the Natural Autoreactive IgG Repertoire in Normal Human Serum, 23 EUR. J.

IMMUNOLOGY 783 (1993) (Ex. A, Tab 11); L. Mouthon et al., Analysis of the Normal

Human IgG Antibody Repertoire: Evidence that IgG Autoantibodies of Healthy Adults

Recognize a Limited and Conserved Set of Protein Antigens in Homologous Tissues,

154 J. IMMUNOLOGY 5769 (1995) (Ex. A, Tab 20)); see also Ex. C, p. 5; Ex. D, pp. 5-6.)

Thus, simply identifying autoantibodies does not indicate autoimmunity. (Ex. A, p. 6;

Ex. C, p. 5; Ex. D, p. 5.) Further, Dr. Kedl opines that “repeated vaccination often

induces cross reactivity with no corresponding impact on autoimmune pathology.” (Ex.

A, p. 6.) As an example, he highlights the broadly neutralizing antibodies against HIV.

(Id.) Dr. Kedl explains that HIV-specific broadly neutralizing antibodies are “rare and a

handful have been studied in an attempt to understand what endows them with their

capacity to neutralize HIV across numerous strains and clades.” (Id.) Besides targeting

HIV surface proteins, he notes that they are also often highly cross reactive with

numerous self-antigens. (Id. (citing Laurent Verkoczy & Marilyn Diaz, Autoreactivity in

HIV-1 Broadly Neutralizing Antibodies: Implications for Their Function and Induction by

Vaccination, 9 CURRENT OP.: HIV & AIDS 224 (2014) (Ex. A, Tab 26); Barton F. Haynes

et al., Cardiolipin Polyspecific Autoreactivity in Two Broadly Neutralizing HIV-1

Antibodies, 308 SCIENCE 1906 (2005) (Ex. A, Tab 10)).) According to Dr. Kedl, “[t]his

self-reactivity actually assists in HIV neutralization without any obvious autoimmune

complications.” (Id. (citing Haynes et al., supra, at Ex. A, Tab 10; John R. Mascola &

Barton F. Haynes, HIV-1 Neutralizing Antibodies: Understanding Nature’s Pathways,

254 IMMUNOLOGICAL REVS. 225 (2013) (Ex. A, Tab 18)).) This, he contends, reinforces

the point that auto-reactivity does not alone equate with pathology. (Id.)

Dr. Kedl opines that there is no relationship between pneumococcal vaccination

and autoantibody formation or autoimmunity. (Ex. A, pp. 7-9.) He contends that

attempts at vaccine-induced neuropathology are “highly variable with documented

failures questioning the entire concept of oligosaccharide/ganglioside molecular mimicry

as a legitimate etiology for GBS.” (Id. at 7.) Even studies that induced neuropathology

could do so only under “excessive and chronic inflammatory conditions.” (Id. (citing

Bowes et al., supra, at Ex. A, Tab 3; Moyano et al., supra, at Ex. A, Tab 21; Yuki et al.,

supra, at Ex. A, Tab 27).) Nor does epidemiological data on the use of the Prevnar

vaccine bear out any connection to chronic autoimmune conditions, including GBS. (Id.

at 8.) Dr. Kedl criticizes the case reports cited by Dr. Sheikh, noting that case reports

20

“generally presuppose that a preceding event is a precipitating event” and are therefore

“built around coincidence.” (Id.) He opines that the available epidemiological data,

including the data cited by Dr. Sheikh (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 DIS. 313 (2015) (Ex. 36); Haber et al., supra, at Ex. 161; T.F. Schwarz et al.,

A Randomized, Double-Blind Trial to Evaluate Immunogenicity and Safety of 13-Valent

Pneumococcal Conjugate Vaccine Given Concomitantly with Trivalent Influenza

Vaccine in Adults Aged ≥ 65 Years, 29 VACCINE 5195 (2011) (Ex. 38); Ravishankar,

supra, at Ex. 160), have failed to document even a single case of GBS after Prevnar 13

vaccination, despite taking into account more than 60,000 vaccine doses. (Ex. A, p. 8

(citing Lisa A. Jackson et al., Immunogenicity and Safety of a 13-Valent Pneumococcal

Conjugate Vaccine in Adults 70 Years of Age and Older Previously Vaccinated with 23-

Valent Pneumococcal Polysaccharide Vaccine, 31 VACCINE 3585 (2013) (Ex. A, Tab

12); Lisa A. Jackson et al., Immunogenicity and Safety of a 13-Valent Pneumococcal

Conjugate Vaccine Compared to a 23-Valent Pneumococcal Polysaccharide Vaccine in

Pneumococcal Vaccine-Naive Adults, 31 VACCINE 3577 (2013) (Ex. A, Tab 13)).)

Dr. Kedl opines that Dr. Steinman’s phospholipid-based mimicry is unsound

because “phospholipids are ubiquitous in human tissue and not unique to myelin.” (Ex.

I, p. 3.) He stresses that all membranes of all cells in the body consist of phospholipids

– including phosphatidyl-ethanolamine, phosphatidyl-choline, and phosphatidylserine.

(Id.) Dr. Kedl explains that all three lipids are components of the outer (phosphatidyl-

ethanolamine and phosphatidyl-choline) and inner (phosphatidylserine and

phosphatidyl-ethanolamine) cell surface membranes in every cell of the body. (Id.)

Therefore, he insists that “there is no reliable reason why antibodies would choose to

preferentially target the phosphoglycerol lipids in the myelin sheath of peripheral nerves

for pathogenesis and not in every other cell in the body.” (Id.) Similarly confounding,

Dr. Kedl opines that IVIg contains antibodies specific for numerous phospholipids. (Id.

(citing Ilan Krause et al., Anti-DNA and Antiphospholipid Antibodies in IVIG

Preparations: In Vivo Study in Naive Mice, 18 J. CLINICAL IMMUNOLOGY 52 (1998) (Ex. I,

Tab 1)).) He insists the amount of anti-phospholipid activity in IVIg treated patients

actually increases immediately following infusion. (Id. at 3-4 (citing Nakos et al., supra,

at Ex. 142).)

Although the therapeutic underpinnings of IVIg are not completely understood,

Dr. Kedl opines that high amounts of phospholipid-specific antibodies in IVIg more likely

supports a therapeutic role for these antibodies and, given that phospholipid reactivity

does not serve as a barrier to IVIg’s therapeutic efficacy against autoimmune

complications, “it is inconceivable how it can automatically equate with autoimmune

pathology.” (Ex. I, pp. 4-5.) This, he explains, is precisely what the authors concluded

in Gilburd et al. (Id. at 5 (citing Gilburd et al., supra, at 141.) Dr. Kedl suggests the

Gilburd et al. study’s conclusion regarding the presence of anti-phospholipid antibodies

in GBS patients does not need revision. (Id.) Gilburd et al. concluded that the

antiphospholipid antibodies they found in GBS patients were probably “produced as a

21

result of the myelin damage, rather than caused by the inflammatory demyelination.”

(Id. (quoting Gilburd et al., supra, at Ex. 141, p. 6).) Dr. Kedl suggests the available

data confirms this conclusion. (Id.) He explains the presence of phospholipid-specific

antibodies “may assist in the clearance of cellular debris that can instigate further

detrimental inflammatory processes.” (Id. at 4.) Under normal conditions,

phosphatidylserines are sequestered away from the extracellular environment; but

during apoptosis, phosphatidylserine “is flipped from the inner to the outer membrane

where it can be recognized by specific receptors found on scavenger cells whose job it

is to clear the system of dying cells and cellular debris.” (Id. at 5.) “These scavenger

cells also have receptors for the tail end of antibodies to help facilitate similar clearance

of antibody-bound viruses and bacteria.” (Id.) Dr. Kedl explains that

phosphatidylserine-specific antibodies may also assist in this process by binding to

cellular debris that may promote inflammation and disrupt local tissue function, like what

is seen in peripheral nerves during GBS. (Id.) Dr. Kedl opines that this could clarify any

association of these antibodies with the onset of autoimmunity as “a harbinger, not an

executioner of tissue dysfunction.” (Id.)

Dr. Kedl also opines that Dr. Steinman’s theory of vaccine causation by

molecular mimicry between CRM197 and contactin-1 is unpersuasive. (Ex. I, pp. 6-8.)

He indicates the E-values for the similarities between CRM197 and contactin-1 are

almost 2 orders of magnitude higher than the search engine’s default value (0.05). 12

(Id. at 6.) He also criticizes Dr. Steinman for comparing CRM197 to contactin-1, rather

than “BLASTing” the sequence of CRM197 against the entire genome. (Id. at 6-7.) Dr.

Kedl suggests this choice was made because Dr. Steinman believes this is a neuron

specific protein. (Id. at 6.) Yet, Dr. Kedl insists that contactin-1 expression is not

isolated to nervous tissue. (Id.) For petitioner to have generated an immune response

with meaningful cross reactivity to contactin-1, Dr. Steinman must also to explain why

petitioner did not then experience any circulatory symptoms. (Id.) Additionally, Dr. Kedl

opines that the 5 out of 10 similarity between the CRM197 epitope (WEQAKALSVE)

and contactin-1 is insignificant. (Id. at 6-7.) In order for the 5 out of 10 similarity to be

significant, Dr. Kedl suggests that Dr Steinman must believe that contactin-1 is the only

protein across the human genome that has this level of similarity with this short

sequence from CRM197. (Id.) Following this logic, Dr. Kedl declares if more proteins in

the human genome could be identified with the same or better similarity to this epitope,

12

Because CRM197 had also been referenced by petitioner’s experts prior to Dr. Steinman’s entry in the

case, this was also previously discussed by Dr. Kedl. In an earlier report, Dr. Kedl opines that the

literature purporting to demonstrate peptide sequence similarity between CRM197 and myelin P0 are

“pure speculation.” (Ex. D, p. 3.) He contends that there is no basis in experimentation for this theory;

and the conclusions of the authors are questionable, given the E-value of the regions of similarity

identified in the BLAST results. (Id.) In that context, Dr. Kedl explains that the BLAST search itself has a

“built-in statistical metric,” the E-value, which is designed to inform whether similarities identified within the

search results have a chance of being “anything more than random.” (Id.) Silvanovich et al. concluded

that any E-value greater than 0.00000039 reflects a similarity that is “more than likely irrelevant.” (Id.

(citing Andre Silvanovich et al., The Use of E-Scores to Determine the Quality of Protein Alignments, 54

REGUL. TOXICOLOGY & PHARMACOLOGY S26 (2009) (Supp. Oct. 23-25, 2007) (Ex. D, Tab 4)).) Dr. Kedl

notes “the E-values of any similarities between CRM197 and Myelin P0 fall above this cutoff by many

orders of magnitude . . . rendering them meaningless.” (Id. (citing Ex. D, app. A at 10-15).)

22

“then once again Dr. Steinman would be left to provide a valid scientific rationale for the

immune systems’ curious obsession with CNTN1 over and above all other targets that

are as good if not better.” (Id. at 7.) In fact, Dr. Kedl performed a BLAST search

against the entire catalog of predicted human proteins encoded in the genome and

found more than 3000 sequences identified with similar, “if not better,” homology to

WEQAKALSVE than contactin-1. (Id.)

Collectively, Dr. Kedl opines that these shortcomings “contradict all underlying

assumptions of molecular mimicry as a model, failing to meet the demands of Althen

prong one for identifying a persuasive and medically reliable theory of vaccine

causation.” (Ex. I, p. 8.)

ii. Brian C. Callaghan, M.D., M.S. 13

Respondent filed one expert report from Dr. Callaghan. (Ex. G.) Dr. Callaghan

opines that petitioner likely developed GBS 22 days after his Prevnar 13 vaccination.

(Id. at 3.) He added that:

While Dr. Chaudhry believed the GBS diagnosis was questionable due to

the lack of confirmatory testing and application of the Brighton criteria, in

this particular case, petitioner’s history, examination, treatment response,

and subsequent clinical course are all consistent with a diagnosis of GBS.

Lumbar puncture and electrodiagnostic testing were not performed, but

GBS remains the most likely diagnosis.

(Id.) However, he maintains that there is no convincing evidence to support a causal

association with Prevnar vaccination and GBS. (Id.)

Dr. Callaghan cites the Haber et al. study where “the authors performed a data

mining analysis that did not reveal more cases of GBS than would be expected in the

general population and did not identify any new or unexpected [adverse events].” (Ex.

G, p. 3 (citing Haber et al., supra, at Ex. 161).) “Specifically, the authors applied

empirical Bayesian data mining methods to identify disproportionality of vaccine-

adverse event pairs stratified by age group, sex, and by the year the reports were

13

Dr. Callaghan received his medical degree from the University of Pennsylvania Medical Center in

Philadelphia, Pennsylvania, before going on to complete an internship in preliminary medicine and a

residency in neurology at the same university. (Ex. H, p. 1.) He completed a neuromuscular fellowship

and a fellowship in the Center of Healthcare Research and Transformation Policy at the University of

Michigan Health System in Ann Arbor, Michigan, and then went on to receive a master’s degree in clinical

research design and statistical analysis from the same university. (Id.) Dr. Callaghan is board certified in

psychiatry and neurology, and electrodiagnostic medicine. (Id.; Ex. G, p. 1.) He maintains a medical

license and a controlled substance license in Michigan. (Ex. H, p. 1.) He currently works as an associate

professor of neurology at the University of Michigan Health System and a staff physician in the

Department of Neurology at the VA Ann Arbor Health System. (Id. at 1-2; Ex. G, p. 1.) He is a

neuromuscular specialist with an interest in patients with neuropathies, and he has seen an estimated 50

patients with GBS. (Ex. G, p. 1.) He has also published over 120 peer-reviewed articles, abstracts, and

book chapter, mostly focusing on neuropathies, and including appropriate diagnostic evaluation and

treatment of such. (Id.; Ex. H, pp. 10-17.)

23

received.” (Id. (citing Haber et al., supra, at Ex. 161).) “While GBS was not seen more

than expected in the general population, vaccination site cellulitis, local reaction, skin

reaction, and skin swelling were all found to be more common than expected.” (Id.

(citing Haber et al., supra, at Ex. 161).) Dr. Callaghan suggests that this analytic

approach therefore can identify vaccine complications. (Id.) Petitioner’s experts

provide 2 case reports of GBS after Prevnar vaccination. (Id.) Dr. Callaghan stresses,

however, that “case reports only demonstrate a proximal temporal relationship between

Prevnar vaccination and GBS.” (Id.) Accordingly, he notes that “a proximate temporal

relationship alone is insufficient to show causation.” (Id.)

Dr. Callaghan contends that Dr. Sheikh provides no data specific to the Prevnar

vaccine for any of his proposed mechanisms. (Ex. G, p. 4.) By providing seven

possible mechanisms, Dr. Callaghan insists that it is clear that there is no mechanism

with convincing evidence to support Prevnar vaccination leading to GBS. (Id.) In

response to the Vardhini et al. article cited by petitioner, Dr. Callaghan stresses that the

study sought to identify mechanisms by which mycobacterium leprae cause nerve injury

and not for Prevnar vaccination to cause GBS. (Id. (citing Vardhini et al., Comparative

Proteomics of the Mycobacterium leprae Binding Protein Myelin P0: Its Implication in

Leprosy and Other Neurodegenerative Diseases, 4 INFECTION, GENETICS, & EVOLUTION

21 (2004) (Ex. 48)).) Petitioner’s expert suggests that petitioner’s genetic uniqueness

led to Prevnar being able to cause GBS, but Dr. Callaghan notes there is no data about

the petitioner’s genetics that could have led to his GBS. (Id.) Petitioner’s expert opines

that “there are four criteria for molecular mimicry, but that these should not be the

standard for demonstrating this phenomenon.” (Id.) Dr. Callaghan opines the Prevnar

vaccination does not meet any of these four criteria. (Id.) Nor does petitioner’s expert

provide a sound rationale for the use of other criteria. (Id.) Dr. Callaghan agrees with

respondent’s experts, Drs. Chaudhry and Kedl, “that there is no evidence of a biologic

mechanism more likely than not linking Prevnar vaccination to GBS either provided by

petitioner’s experts or in the medical literature. (Id.) He concludes “petitioner likely

suffered from GBS, but the cause in unclear.” (Id.)

V. Discussion

a. Althen prong one

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

showing that the subject vaccine can cause the type of injury alleged. Pafford ex rel.

Pafford v. Sec’y of Health & Human Servs., 451 F.3d 1352, 1355-56 (Fed. Cir. 2006)

(quoting Pafford v. Sec’y of Health & Human Servs., No. 01-0165V, 2004 WL 1717359,

at *4 (Fed. Cl. Spec. Mstr. July 16, 2004)). Such a theory need only be “legally

probable, not medically or scientifically certain.” Knudsen, 35 F.3d at 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 ex rel. Andreu v. Sec’y of Health & Human Servs., 569 F.3d 1367,

1378-79 (Fed. Cir. 2009) (citing Capizzano v. Sec’y of Health & Human Servs., 440

F.3d 1317, 1325-26 (Fed. Cir. 2006)). However, “[a] petitioner must provide a

24

‘reputable medical or scientific explanation’ for [the proposed causal] theory. While it

does not require medical or scientific certainty, it must still be ‘sound and reliable.’”

Boatmon, 941 F.3d at 1359 (quoting Knudsen, 35 F.3d at 548-49).

As with many cases in the Program, petitioner’s theory involves molecular

mimicry. Molecular mimicry is a concept with several constituent parts whereby (1) a

susceptible host (2) encounters a foreign antigen that has sufficient similarity

(“homology”) with components of host tissue such that (3) the immune system “cross

reacts,” producing antibodies that attack the host tissue instead of the foreign antigen to

(4) ultimately cause disease or injury. (INST. OF MED., ADVERSE EFFECTS OF VACCINES:

EVIDENCE AND CAUSALITY (2012) [hereinafter IOM 2012 Report] (Ex. E, Tab 12, p. 10);

Robert S. Fujinami et al., Molecular Mimicry, Bystander Activation, or Viral Persistence:

Infections and Autoimmune Disease, 19 CLINICAL MICROBIOLOGY REVS. 80 (2006) (Ex.

166).) Molecular mimicry “is a generally accepted scientific principle, [but] mere

invocation of the scientific term does not carry a petitioner’s burden in a Program case.”

Deshler v. Sec’y of Health & Human Servs., No. 16-1070V, 2020 WL 4593162, at *20

(Fed. Cl. Spec. Mstr. July 1, 2020) (citing Forrest v. Sec’y of Health & Human Servs.,

No. 14-1046V, 2019 WL 925495, at *3 (Fed. Cl. Spec. Mstr. Jan. 18, 2019)). This is

because “the finding of sequence homology does not necessarily mean the similarity

has significance to the immune system.” Tullio v. Sec’y of Health & Human Servs., No.

15-51V, 2019 WL 7580149, at *15 (Fed. Cl. Spec. Mstr. Dec. 19, 2019), aff’d, 149 Fed.

Cl. 448 (2020); see also Caredio ex rel. D.C. v. Sec’y of Health & Human Servs., No.

17-0079V, 2021 WL 4100294, at *31 (Fed. Cl. Spec. Mstr. July 30, 2021)

(“[D]emonstration of homology alone is not enough to establish a preponderant

causation theory.”) (citing Schultz v. Sec’y of Health & Human Servs., No. 16-539V,

2020 WL 1039161, at *22 n.24 (Fed. Cl. Spec. Mstr. Jan. 24, 2020))), mot. for rev.

den’d, No. 17-79V, 2021 WL 6058835 (Fed. Cl. Dec. 3, 2021). However, as noted

above, petitioners in this program are not required to establish scientific certainty.

Therefore, prior cases have expressed with regard to the application of molecular

mimicry that “[t]he line must be drawn somewhere between speculation and certainty.”

Brayboy v. Sec’y of Health & Human Servs., No. 15-183V, 2021 WL 4453146, at *19

(Fed. Cl. Spec. Mstr. Aug. 30, 2021). Thus, for example, in Brayboy, an omnibus

proceeding addressing autoimmune premature ovarian insufficiency, the special master

found it sufficient that the petitioners “identified cross-reaction between components of

the vaccine and proteins in the body that are directly responsible for the health and

productivity of the organ at issue” and further expressed that requiring additional steps,

or insisting on direct, testable evidence, would impermissibly heighten petitioners’

burden of proof. Id.

GBS is an acute inflammatory polyneuropathy affecting the peripheral nerves

and, in the case of AIDP, most notably affecting myelin tissue. (Ex. 68, p. 3.) While the

condition is believed to be of an autoimmune etiology, the pathogenesis of GBS is

incompletely understood. (Nakos et al., supra, at Ex. 142; Gilburd et al., supra, at Ex.

141; Ex. 18, p. 7.) Petitioner’s experts opine that the current understanding of GBS

provides some basic support for their opinion that the Prevnar 13 vaccine can cause

GBS. (See Ex. 80, p. 5; Ex. 106, pp. 4-5; Ex. 129, pp. 27-28.) Although there is no

25

established association between Streptococcus pneumonia and GBS (Ex. E, pp. 15, 17-

18), it is generally accepted that a number of different infectious antigens can cause

GBS, including unspecified upper respiratory infections (Ex. 18, p. 4; Ex. E, pp. 13, 15;

NAT’L INST. OF NEUROLOGICAL DISORDERS & STROKES, NAT’L INST. HEALTH, GUILLAIN-

BARRÉ SYNDROME FACT SHEET (2020) (Ex. 138); B.C. Jacobs et al., The Spectrum of

Antecedent Infections in Guillain-Barré Syndrome: A Case-Control Study, 51

NEUROLOGY 1110 (1998) (Ex. 20)). This includes both viral and bacterial infections.

(Ex. 18, p. 4; Bianca van der Berg et al., Guillain-Barré Syndrome Associated with

Preceding Hepatitis E Virus Infection, 82 NEUROLOGY 491 (2012) (Ex. 21).) Additionally,

for at least one of these antigens, C. jejuni, there is sufficient proof to conclude that

molecular mimicry is the mechanism of causation leading to GBS, albeit resulting

primarily in the axonal subtype of GBS and involving a molecular mimic not at issue

here. (Ex. 163, p. 5; Ex. E, p. 15; Nobuhiro Yuki, Guillain-Barré Syndrome and Anti-

Ganglioside Antibodies: A Clinician-Scientist’s Journey, 88 PROC. JAPAN ACAD.: SERIES B

299 (2012) (Ex. 169).) Evidence also supports homology between various other

antigens and myelin tissue. (See IOM 2012 Report, supra, at Ex. E, Tab 12, p. 11

(hepatitis B virus); Richard A.C. Hughes & Jeremy H. Rees, Clinical and Epidemiologic

Features of Guillain-Barré Syndrome, 176 J. INFECTIOUS DISEASES S92, S94 (Supp.

1997) (Ex. 53, p. 3) (“There is no doubt that rabies vaccines produced in nervous

system tissue carried a risk of inducing GBS, which can readily be explained as being

caused by immunization with myelin antigens.”).) In that regard, there is little question

that multiple antigens are implicated as causes of GBS. Additionally, respondent’s

expert agrees that at least some formulations of the flu vaccine have been identified as

a cause of GBS. (Ex. G, p. 3.) Without equating the flu vaccine and the Prevnar 13

vaccine, petitioner’s experts opine that, broadly speaking, this demonstrates that the

immune response to vaccination, and not only active infection, is sufficient to cause

GBS. (Ex. 129, p. 6.)

In some prior cases, this background information has partly informed the special

masters’ analysis of a petitioner’s theory of causation with respect to GBS. See, e.g.,

J.G. v. Sec’y of Health & Human Servs., No. 20-664V, 2023 WL 2752634, at *30 (Fed.

Cl. Spec. Mstr. Feb. 13, 2023) (observing that “[t]he experts do not dispute the theory of

molecular mimicry, or that it is a sound and reliable theory generally as it relates to

GBS” and that “[m]olecular mimicry has been accepted as a sound and reliable theory

in many Vaccine Program cases dealing with demyelinating conditions, including GBS”);

Osso v. Sec’y of Health & Human Servs., No. 18-575V, 2023 WL 5016473, at *21 (Fed.

Cl. Spec. Mstr. July 13, 2023) (molecular mimicry accepted as a “sound and reliable

theory”); Harris v. Sec’y of Health & Human Servs., No. 18-944V, 2023 WL 2583393, at

*22 (Fed. Cl. Spec. Mstr. Feb. 21, 2023) (finding that “the fact that GBS is well accepted

as an autoimmune condition with a wide variety of suspected antigenic triggers,

inclusive of antigens from both infection and vaccination, provides meaningful evidence

supporting petitioner's burden of proof with respect to Althen prong one”). But see

Trollinger v. Sec’y of Health & Human Servs., No. 16-473V, 2023 WL 2521912, at *30

(Fed. Cl. Spec. Mstr. Feb. 17, 2023) (finding that “Dr. Steinman’s theory had a one-size-

fits-all quality, in which he strained to shoehorn the science behind the flu-GBS

association into the context of the pneumococcal vaccine” and further noting that, “[i]f

26

this were sufficient to establish that this particular vaccine ‘can cause’ GBS, it is hard to

imagine the theory not also applying to each and every one of the sixteen Program-

covered vaccines/vaccine antigenic components”), mot. for rev. den’d, 167 Fed. Cl. 127

(2023). Although only the flu vaccine is presumed to be a cause of GBS in this program

(42 C.F.R. § 100.3(a)), petitioners have been found entitled to compensation in at least

isolated instances for GBS caused by many other vaccines. This includes vaccines that

target both viruses and bacteria. See, e.g., Salmins v. Sec’y of Health & Human Servs.,

No. 11-140V, 2014 WL 1569478, at *14 (Fed. Cl. Spec. Mstr. Mar. 31, 2014) (finding

that HPV vaccine “can cause” GBS); Peugh v. Sec’y of Health and Human Servs., No.

99-638V, 2007 WL 1531666, at *17 (Fed. Cl. Spec. Mstr. May 8, 2007) (finding as part

of an omnibus proceeding that hepatitis B vaccine can GBS); Whitener v. Sec’y of

Health & Human Servs., No. 06-0477V, 2009 WL 3007380, at *20 (Fed. Cl. Spec. Mstr.

Sept. 2, 2009) (finding that meningococcal vaccine can cause GBS); Koller v. Sec’y of

Health & Human Servs., No. 16-439V, 2021 WL 5027947, at *7-20 (Fed. Cl. Spec. Mstr.

Oct. 8, 2021) (finding that pneumococcal conjugate vaccine, Prevnar 13, can cause

GBS); Mohamad v. Sec’y of Health & Human Servs., No. 16-1075V, 2022 WL 711604,

at *9-18 (Fed. Cl. Spec. Mstr. Jan. 27, 2022) (finding that Tdap vaccine can cause

GBS); J.G., 2023 WL 2752634, at *29-32 (finding that hepatitis A vaccine can cause

GBS). 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.

Within that context, Dr. Steinman opines that the Prevnar 13 vaccine can be

considered among the many other causes of GBS, presenting several pieces of medical

literature to demonstrate that (1) the Prevnar 13 vaccine contains phosphoglycerol

groups that are necessary to the vaccine’s immunogenicity (Ex. 129, pp. 7, 9-16 (citing

Chang et al., supra, at Ex. 143; Prevnar 13 Package Insert, supra, at Ex. 140; Bryson et

al., supra, at Ex. 146)); (2) the phosphate portion of the phospholipid molecule has

immune reactivity in myelin tissue, albeit with regard to a different demyelinating

condition (multiple sclerosis) (Id. at 7 (citing Ho et al., supra, at Ex. 136)); (3) GBS

patients develop anti-phospholipid antibodies (Id. at 7-8 (citing Nakos et al., supra, at

Ex. 142; Gilburd et al., supra, at Ex. 141)), and (4) these antibodies are cross-reactive

with phospholipids present in myelin tissue (Id. (citing Gilburd et al., supra, at Ex. 141)).

Dr. Steinman’s theory does not involve the anti-ganglioside antibodies that are most

commonly associated with GBS. However, literature filed in this case indicates that less

than half of GBS patients have anti-ganglioside antibodies. (Gorenjac, supra, at Ex. A,

Tab 6, p. 1; Koga et al., supra, at Ex. A, Tab 14, p. 6 tbl.2.) Moreover, on this record,

respondent’s expert, Dr. Kedl, stresses that the association between anti-ganglioside

antibodies and GBS remains clinically unproven. (Ex. A, p. 6.) Thus, we do not actually

know the full scope of the antibodies that may be implicated in the pathology of GBS,

leaving little reason to doubt Dr. Steinman’s theory on that basis. (See, e.g., Christiaan

Fokke et al., Diagnosis of Guillain-Barré Sydnrome and Validation of Brighton Criteria,

137 BRAIN 137 (2014) (Ex. E, Tab 4, p. 2) (explaining that “[re]cent studies indicate that

Guillain-Barré syndrome consists of a spectrum of neuropathic disorders that may differ

in underlying pathogenesis and clinical manifestations”); accord Gross v. Sec’y of

Health & Human Servs., No. 17-1075V, 2022 WL 9669651, at *36 (Fed. Cl. Spec. Mstr.

27

Sept. 22, 2022) (indicating that “the literature filed by the parties does not support the

notion that gangliosides are the only player in the game of molecular mimicry”).) To this

point, I have previously emphasized that the “S” in GBS stands for “syndrome” and that

“GBS variants are generally believed to have a multitude of both clinical presentations

and causes,” McGill v. Sec’y of Health & Human Servs., No. 15-1485V, 2023 WL

3813524, at *27 n.16 (Fed. Cl. Spec. Mstr. May 11, 2023), raising the question of

whether a single causal theory can explain every instance of GBS, post-vaccination or

otherwise.

I have previously concluded that Dr. Steinman’s phosphoglycerol theory is sound

and reliable, and preponderantly supports a legally probable, though not scientifically

certain, theory of causation sufficient to satisfy petitioner’s burden of proof under Althen

prong one, based on the same medical literature cited in this case. Pierson v. Sec’y of

Health & Human Servs., No. 17-1136V, 2022 WL 322836, at *27-31 (Fed. Cl. Spec.

Mstr. Jan. 19, 2022); see also Cooper v. Sec’y of Health & Human Servs., No. 18-

1885V, 2024 WL 1522331, at *13-18 (Fed. Cl. Spec. Mstr. Mar. 12, 2024). I again

reach the same conclusion based on the evidence of record in this case. Additionally,

other special masters have reached similar conclusions based on substantially similar

underlying evidence. Koller, 2021 WL 5027947, at *16-20 (Gowen); Maloney v. Sec’y of

Health & Human Servs., No. 19-1713V, 2022 WL 1074087, at *30-31 (Fed. Cl. Spec.

Mstr. Mar. 17, 2022) (Dorsey); Gross, 2022 WL 9669651, at *35-36 (Dorsey); Sprenger

v. Sec’y of Health & Human Servs., No. 18-279V, 2023 WL 8543435, at *18-19 (Fed. Cl.

Spec. Mstr. Nov. 14, 2023) (Dorsey); Parker v. Sec’y of Health & Human Servs., No. 20-

411V, 2023 WL 9261248, at *20-22 (Fed. Cl. Spec. Mstr. Dec. 20, 2023) (Dorsey);

Anderson v. Sec’y of Health & Human Servs., No. 18-484V, 2024 WL 557052, at *30-31

(Fed. Cl. Spec. Mstr. Jan. 17, 2024) (Dorsey); see also Tracy ex rel. R.S. v. Sec’y of

Health & Human Servs., No. 16-213V, 2022 WL 1125281, at *29-32 (Fed. Cl. Spec.

Mstr. Mar. 30, 2022) (Special Master Sanders accepting a similar theory in the context

of transverse myelitis). 14

However, acceptance of this theory has not been unanimous among special

masters. Bielak v. Sec’y of Health & Human Servs., No. 18-761V, 2023 WL 35509, at

*33-37 (Fed. Cl. Spec. Mstr. Jan. 3, 2023) (Corcoran); Trollinger, 2023 WL 2521912, at

*26-30 (Corcoran); Gamboa-Avila v. Sec’y of Health & Human Servs., No. 18-925V,

2023 WL 6536207, at *25-29 (Fed. Cl. Spec. Mstr. Sept. 11, 2023) (Corcoran), mot. for

rev. den’d, 170 Fed. Cl. 441 (2024), appeal filed, No. 24-1765 (Fed. Cir. May 1, 2024);

Jaye v. Sec’y of Health & Human Servs., No. 20-672V, 2024 WL 3691413, at *14-17

(Fed. Cl. Spec. Mstr. July 18, 2024) (Corcoran); Morrison v. Sec’y of Health & Human

Servs., No. 18-386V, 2024 WL 3738934, at *19-21 (Fed. Cl. Spec. Mstr. July 18, 2024)

14

Other special masters have also found that petitioners have preponderantly established that the

Prevnar 13 vaccine case cause GBS based on the other causal theory Dr. Steinman presented. Byrd v.

Sec’y of Health & Human Servs., No. 20-1476V, slip op. (Fed. Cl. Spec. Mstr. July 8, 2024) (Gowen)

(accepting petitioner’s causal theory based on molecular mimicry between CRM197 and contactin-1);

Anderson, 2024 WL 557052, at *31-32 (Dorsey) (same); Sprenger, 2023 WL 8543435, at *19-20 (Dorsey)

(same); Gross, 2022 WL 9669651, at *36-37 (Dorsey) (same); Maloney, 2022 WL 1074087, at *32

(Dorsey) (same).

28

(Oler). 15 These contrary decisions are not binding on me. Boatmon, 941 F.3d at 1358-

59; Hanlon ex rel. Hanlon v. Sec’y of Health & Human Servs., 40 Fed. Cl. 625, 630

(1998). Nonetheless, I have considered the points raised by these decisions. I simply

reach a different conclusion based on my overall weighing of the evidence on this

record. Notably, even when reaching a different result, there has still been agreement

that record evidence comparable to what has been presented in this case at a minimum

does offer reliable support for the conclusion that phyosphoglycerol is found

in the pneumococcal vaccine; that the immune system produces antibodies

in reaction to the relevant antigens containing the phosphoglycerol; and that

individuals with neuropathies (although some suffer from the

distinguishable disease MS) have been shown in small sample studies to

posses antibodies specific to myelin-containing phospholipids.

Trollinger, 2023 WL 2521912, at *28 (emphasis original). 16

In this case, Respondent’s immunology expert, Dr. Kedl, offers several

arguments to rebut Dr. Steinman’s phosphoglycerol theory; however, none are

persuasive. First, Dr. Kedl disputes the general applicability of molecular mimicry as a

casual theory for how any vaccine can cause GBS. (Ex. A, pp. 4-6; Ex. C, pp. 4-6; Ex.

D, p. 6.) However, a blanket denial of the applicability of the theory would risk

heightening petitioner’s burden of proof. “[T]he 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 F.3d at 1280.

The preponderant standard “does not operate as a sliding scale that varies depending

upon the quantity and quality of scientific evidence that is available,” Caves v. Sec’y of

Health & Human Servs., 100 Fed. Cl. 119, 143 (2011), aff’d, 463 F. App’x 932 (Fed. Cir.

15

Some additional cases were resolved against petitioners based on different theories of causation.

McConnell v. Sec’y of Health & Human Servs., No. 18-1051V, 2022 WL 4008238, at *7-9 (Fed. Cl. Spec.

Mstr. Aug. 19, 2022); Deshler, 2020 WL 4593162, at *19-21.

16

In his most recent decision regarding whether the Prevnar 13 vaccine can cause GBS, Chief Special

Master Corcoran noted that my decision in Cooper “underscored the overlap . . . with the intent of

emphasizing how little separates” the special masters’ disparate findings regarding the persuasiveness of

Dr. Steinman’s causal theory. Jaye, 2024 WL 3691413, at 17 n.20. I at least partly agree with the Chief

Special Master that “the varying outcomes in these cases more likely results from differences of opinion

about the proper application of the Althen prong one evidentiary standard.” Id. However, there have also

been some significant differences in the record evidence of the various decisions weighing the theory Dr.

Steinman presents in this case. For instance, while some prior cases denying compensation for GBS

based on this theory found significance in the distinction between B- and T-cell responses, respondent’s

expert in Cooper specifically disclaimed a hardline distinction between such responses, testifying instead

that “nothing is pure B cell/Tcell”. Compare Cooper, 2024 WL 1522331, at *17, with Deshler, 2020

WL4593162, at *19-20, and Bielak, 2023 WL 35509, at *29-37. More recently, the Morrison decision

turned in part on acceptance of the pathological role of anti-ganglioside antibodies in GBS as suggested

by Dr. Whitton. Morrison, 2024 WL 3738934, at 19-21. Yet, respondent’s expert in this case, Dr. Kedl,

asserts to the contrary that this is “tenuous, speculative and clinically unproven,” and that “the vast

majority of literature stands in sharp contrast to the assertion that there is any causal relationship

between ganglioside-specific antibodies and GBS.” (Ex. A, p. 5, 6.)

29

2012), but nor should the evidence be viewed “through the lens of the laboratorian,”

Andreu, 569 F.3d at 1380. Even the literature cited by respondent, including the IOM,

accepts the general viability of molecular mimicry as a concept. (Yuki et al., supra, at

Ex. A, Tab 27, p. 1; IOM 2012 Report, supra, at Ex. E, Tab 12, p. 10.) Moreover,

molecular mimicry is a well-established theory that has persuasively linked vaccines to

autoimmune conditions, including GBS. See, e.g., Conte v. Sec’y of Health & Human

Servs., No. 17-403V, 2020 WL 5743696, at *23 (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 & Human Servs., No. 11-

707V, 2014 WL 6834557, at *8 (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”).

Second, Dr. Kedl disputes that phosphoglycerol antibodies in the Prevnar 13

vaccine would preferentially target phosphoglycerol lipids in the myelin sheath or the

peripheral nerves without also targeting the other phosphoglycerol-based lipids

throughout the rest of the body. (Ex. I, p. 3.) However, Dr. Steinman explains that it is

biologically plausible for a widespread antigen to trigger organ-specific diseases. (Ex.

163, pp. 4-6.) By way of example, Dr. Steinman points to the well-established

association between C. jejuni and gangliosides, which he describes as “one of the

classic antigens associated with GBS.” (Id. at 5, 10-11.) He notes that gangliosides are

present in the central and peripheral nervous systems, as well as in the bone marrow,

erythrocytes, intestine, liver, spleen, and testis; however, an immune response to

gangliosides in C. jejuni “only leads to GBS,” a peripheral nervous system disorder. (Id.

(citing Yuki, supra, at Ex. 169; Thomas Kolter, Ganglioside Biochemistry, INT’L

SCHOLARLY RSCH. NETWORK BIOCHEMISTRY, Dec. 2012, at 1 (Ex. 170)).)

Third, Dr. Kedl contends that the Nakos et al. study, one of the two studies

showing GBS patients to have anti-phospholipid antibodies, undermines Dr. Steinman’s

theory. Specifically, he points to the fact that the subjects in the Nakos et al. study were

administered IVIg containing anti-phospholipid antibodies. (Ex. I, pp. 3-5 (citing Nakos

et al., supra, at Ex. 142).) Dr. Kedl explains that IVIg is the “only really successful

treatment for GBS” and asserts that “[i]f anti-phospholipid antibodies were a consistent

contributor to neuropathological symptoms, then infusing a large bolus of gamma-

globulin containing anti-phospholipid activity would be contraindicative for GBS, not

therapeutic.” (Id. at 3-4.) However, the Nakos authors do account for the possibility

that an initial increase in anti-phospholipid antibodies could be attributable to the

contents of the IVIg as Dr. Kedl contends, given that the antibodies were significantly

increased one hour after treatment. Nonetheless, they still concluded that it is possible

the gamma-gobulin ultimately has an overall blocking effect on anti-phospholipid

antibodies given that they found the antibodies were subsequently significantly reduced

one day after treatment. (Nakos et al., supra, at Ex. 142, p. 6.) In that regard, Dr. Kedl

concedes that the means by which IVIg has its therapeutic effect are “far from

completely understood.” (Ex. I, p. 5.) Additionally, Dr. Kedl and Dr. Steinman have filed

competing studies with respect to whether commercially available IVIg preparations

generally do contain meaningful levels of these autoantibodies. (Compare Krause et

30

al., supra, at Ex. I, Tab 1 (finding three commercial preparations include significant anti-

phospholipid antibodies but concluding based on a mouse model they are not

pathologic), with Sherer et al., supra, at Ex. 173 (finding five commercial preparations of

IVIg did not include sufficient levels of anti-phospholipid antibodies to be disease

modifying).) The Sherer et al. study cited by Dr. Steinman would seem to rebut Dr.

Kedl’s premise that IVIg contains a “large bolus” of these antibodies. (Ex. I, p. 4.) That

study concluded that IVIg is safe for patients with Hughes syndrome, a disorder known

to be mediated by antiphospholipid antibodies. (Sherer et al., supra, at Ex. 173, pp 1,

3.) Ultimately, Nakos et al. were unable to discern a relationship between antibody

levels and outcomes, which they attributed to the small size of the study and the variety

of possible GBS presentations. (Nakos et al., supra, at Ex. 142, p. 7.) In that regard,

Dr. Steinman stresses that Dr. Kedl’s observation relies on an aspect of the study for

which the authors specified “data not shown.” (Ex. 163, p. 7 (citing Nakos et al., supra,

at Ex. 142, p. 5).) Dr. Steinman cites several potentially confounding variables that

could be reflected in the missing data. (Id. at 7-8.)

Finally, I note briefly that I have also considered the opinions of respondent’s

neurology experts with respect to Althen prong one. Dr. Callaghan questioned the

relevance of the two case reports cited by petitioner’s experts (Hassan El Khatib et al.,

Case Report: Guillain-Barre Syndrome with Pneumococcus – A New Association in

Pediatrics, 11 IDCASES 36 (2018) (Ex. 92); Ravishankar, supra, at Ex. 160), asserting

that they do no more than show a temporal association between infection or vaccination

and injury. (Ex. G, p. 3.) However, although case reports “are not entirely devoid of

evidentiary value,” Kaltenmark ex rel. A.J.K. v. Sec’y of Health & Human Servs., No. 17-

1362V, 2023 WL 8870299, at *30 n.30 (Fed. Cl. Spec. Mstr. Nov. 27, 2023); Paluck ex

rel. Paluck v. Sec’y of Health & Human Servs., 104 Fed. Cl. 457, 475 (2012), this case

does not turn on the availability of case reports. Dr. Callaghan also cited Haber et al.,

as finding that the incidence of GBS did not exceed what would be expected in the

general population. (Ex. G, p. 3 (citing Haber et al., supra, at Ex. 161).) However, in a

prior case, Dr. Callaghan conceded during testimony that the Haber study is not strong

evidence. Cooper, 2024 WL 1522331, at *17 n.17. In any event, petitioner’s experts do

not dispute that GBS is a rare condition. (Ex. 18, p. 4; Ex. 129, p. 6.) Dr. Chaudhry

argued that it is unlikely that the Prevnar 13 vaccine, which protects against

Streptococcus pneumonia, could cause GBS where there has been no established

relationship between the bacterium and GBS. (Ex. E, pp. 15, 17-18.) Although helpful

when present, petitioners need not “demonstrate that a vaccine’s infectious counterpart

is a known-disease trigger.” Morrison, 2024 WL 3738934, at *18. Petitioners similarly

need not present epidemiologic evidence to support their claim. Andreu, 569 F.3d at

1378. Thus, although respondent’s neurology experts’ contentions represent at least

some evidence inconsistent with petitioner’s theory, they are insufficient to contradict

the evidence presented in support of Dr. Steinman’s theory.

In light of the above, petitioner has satisfied the first Althen prong by

preponderant evidence.

31

b. Althen prong two

The second Althen prong requires preponderant proof of a logical sequence of

cause and effect, which is usually supported by facts derived from petitioner’s medical

records. Althen, 418 F.3d 1278; Andreu, 569 F.3d at 1375-77; Capizzano, 440 F.3d at

1326; Grant, 956 F.2d at 1148. Medical records are generally viewed as trustworthy

evidence. Cucuras ex rel. Cucuras v. Sec’y of Health & Human Servs., 993 F.2d 1525,

1528 (Fed. Cir. 1993). These records are generally contemporaneous to the medical

events and “contain information supplied to or by health professionals to facilitate

diagnosis and treatment of medical conditions. With proper treatment hanging in the

balance, accuracy has an extra premium.” Id. However, medical records and/or

statements of a treating physician’s views do not per se bind the special master.

§ 300aa-13(b)(1) (providing that “[a]ny such diagnosis, conclusion, judgment, test result,

report, or summary shall not be binding on the special master or court”); Snyder ex rel.

Snyder v. Sec’y of Health & Human Servs., 88 Fed. Cl. 706, 746 n.67 (2009) (reasoning

that “nothing . . . mandates that the testimony of a treating physician is sacrosanct—that

is must be accepted in its entirety and cannot be rebutted”). A petitioner may support a

cause-in-fact claim through presentation of either medical records or expert medical

opinion. See § 300aa-13(a). The special master is required to consider all relevant

evidence of record, draw plausible inferences, and articulate a rational basis for the

decision. Winkler v. Sec’y of Health & Human Servs., 88 F.4th 958, 963 (Fed. Cir.

2023) (citing Hines, 940 F.2d at 1528).

Although there was some initial disagreement regarding diagnosis, Dr. Callaghan

ultimately concedes on behalf of respondent that petitioner likely suffered from GBS.

(Ex. G, pp. 3-4.) Petitioner’s diagnostic work up was limited; however, Dr. Sheikh

opines, and Dr. Callaghan agrees, that petitioner’s positive response to IVIg supports

his GBS diagnosis. (Id. at 3; Ex. 51, pp. 9-10; Ex. 16, pp. 519-24, 531; Ex. 2, p. 204.)

Additionally, Dr. Sheikh opines that, although diagnostically helpful, a spinal tap or

nerve conduction study only provide indirect evidence of demyelination or inflammation

and “[t]he only definitive way of demonstrating immune infiltration and demyelination is

nerve pathology, which is not [the] standard of care for the management of GBS.” (Ex.

51, p. 9.) He persuasively opines that petitioner’s treaters did not deem a spinal tap or

nerve conduction study diagnostically necessary as petitioner’s clinical presentation,

responsiveness to IVIg treatment, and clinical course were all consistent with GBS. (Id.

at 9-10.)

With diagnosis established, the fact that petitioner has satisfied Althen prongs

one and three is significant to the Althen prong two analysis. See Capizanno,440 F.3d

at 1326. Ordinary medical care offers little beyond clinical history that would confirm the

cause of GBS. Nonetheless, petitioner points to several medical records to support his

contention that his treating physicians attributed his condition to his Prevnar 13

vaccination, although he acknowledges that none of his physicians “expressed absolute

certainty as to vaccine causality.” (ECF No. 119, pp. 76-77 (citing Ex. 2, p. 95; Ex. 5, p.

15; Ex. 15, p. 29).) On at least one occasion, petitioner’s treating neurologist noted his

recent Prevnar vaccination before providing a differential diagnosis of acute

32

demyelinating polyneuropathy. (Ex. 2, pp. 278-79.) Moreover, petitioner’s treating

physicians added the Prevnar vaccine to his allergy list (Id. at 91, 204; Ex. 4, p. 51; Ex.

15, p. 40), demonstrating at least some evidence that their opinion was not limited to a

temporal association between the vaccine and injury. See Andreu, 569 F.3d at 1376-77

(“A treating physician’s recommendation to withhold a particular vaccination can provide

probative evidence of a causal link between the vaccination and the injury a claim has

sustained.”); see also, e.g., Capizzano, 440 F.3d at 1320, 1326-27 (concluding that the

chief special master erred in part because he failed to consider the fact that petitioner’s

treater decided that she should not receive the third hepatitis B vaccination in the series

as evidence in support of Althen prong two); Kelley v. Sec’y of Health & Human Servs.,

68 Fed. Cl. 84, 100 (2005) (relying in part on petitioner’s treater’s reported hesitancy to

administer further tetanus shots as evidence in support of the second Althen prong).

Respondent’s additional argument that petitioner’s treating neurologist’s opinion should

be given less weight specifically because it does “not discuss a theory of causation,”

(ECF No. 123, p. 41), also fails as “[a]ny expectation that treating physicians will record

the precise biological theories behind their belief that a patient’s condition was caused

by a particular trigger is discordant with the reality of medical treatment.” Campbell v.

Sec’y of Health & Human Servs., 97 Fed. Cl. 650, 667 (2011).

Additionally, petitioner’s experts opine that the Prevnar 13 vaccine “did cause”

his GBS. His experts readily admit that he underwent a limited work up; however, they

suggest that this fact underscores that there was low clinical suspicion of any alternative

cause and no alternate explanation emerged. (See Ex. 18, p. 9; Ex. 163, p. 27.) They

point to the fact that there is no evidence of upper respiratory tract infection, diarrheal

illness, or any other significant medical event preceding onset of petitioner’s GBS. (Ex.

18, p. 9; Ex. 51, p. 3; Ex. 163, p. 27.) Petitioner need not rule out all alternative causes;

however, “petitioner is certainly permitted to use evidence eliminating other potential

causes to help carry the burden on causation.” Walther, 485 F.3d at 1151. Thus, it is

notable that there was no other cause that petitioner’s treaters believed to be the more

likely cause of his GBS. See Campbell, 97 Fed. Cl. at 671; Capizzano v. Sec’y of

Health & Human Servs., No. 00-759V, 2006 WL 3419789, at *11 (Fed. Cl. Spec. Mstr.

Nov. 8, 2006).

Setting aside the possible acute causes of GBS, respondent also argues that

petitioner must demonstrate that “his pre-existing conditions were not the cause of his

symptoms and resulting injuries.” (ECF No. 123, pp. 42.) Respondent asserts that it is

petitioner’s burden “to confront other possible grounds of causation evidence in the

record.” (Id. at 42-43 (citing Capizzano, 440 F.3d at 1327).) While this is true, it is also

the case that petitioners do not bear a burden to “discount every potential cause that

exists within the entire realm of possibility.” Pafford ex rel. Pafford v. Sec’y of Health &

Human Servs., 64 Fed. Cl. 19, 35 (2005), aff’d, 451 F.3d 1352 (Fed. Cir. 2006). Here,

respondent presents a broad list of prior conditions without any specific suggestion that

any of the identified conditions either explains petitioner’s post-vaccination presentation

or constitutes any known cause of GBS. 17 It is difficult to see how this line of argument

17

Respondent simply notes without explanation that petitioner’s pre-existing conditions include:

hypertension, diabetes mellitus, hyperlipidemia, coronary artery disease, status-post coronary artery

33

is not entirely obviated by Dr. Callaghan’s ultimate clinical assessment on respondent’s

behalf that petitioner was suffering from idiopathic GBS. (Ex. G, p. 4.) Dr. Callaghan,

opines of petitioner’s GBS that “the cause is unclear.” 18 (Id.)

Dr. Kedl also opines that, because GBS is frequently preceded by infection, an

undetected, subclinical infection is a more likely cause of petitioner’s GBS. (Ex. A, pp.

9-10.) However, the Federal Circuit has previously held that “statistical likelihood alone

cannot support actual causation.” Boatmon, 941 F.3d at 1363; see also Knudsen, 35

F.3d at 550 (“The bare statistical fact that there are more reported cases of viral

encephalopathies than there are reported cases of [post-vaccination] encephalopathies

is not evidence that in a particular case an encephalopathy following . . . vaccination

was in fact caused by a viral infection . . . and not caused by the . . . vaccine.”).

Moreover, Dr. Kedl’s arguments in this regard are couched in his ultimate disagreement

with petitioner’s causal theory, which has already been resolved under Althen prong

one.

Accordingly, petitioner has satisfied his burden of preponderantly proving a

logical sequence of cause and effect under the second Althen prong.

c. Althen prong three

Under the third Althen prong, a petitioner must demonstrate a “proximate

temporal relationship” between the subject vaccination and the alleged injury. Althen,

418 F.3d at 1278. To do this, petitioner must provide “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 (citations omitted).

In this case, the parties agree that petitioner experienced onset of symptoms

within 22 days, or approximately 3 weeks, following his Prevnar 13 vaccination. (Ex. G,

p. 3; Ex. 18, p. 9; Ex. 129, p. 27.) Petitioner’s experts opine that this timeframe is

consistent with both petitioner’s proposed medical theory and the medical literature

concerning timing of post-vaccination GBS. (Ex. 129, p. 27 (citing Schonberger, supra,

at Ex. 162).) Respondent argues, however, that petitioner’s experts’ reliance on

evidence pertaining to the flu vaccine to evidence the appropriate timeframe for onset in

bypass graft and stent placement, ischemic cardiomyopathy and related congestive heart failure,

paroxysmal atrial fibrillation, prostatic hypertrophy, venous insufficiency, peripheral vascular disease,

GERD, multiple previous surgeries, a history of multifocal paresthesia in 2012 related to vitamin B12

deficiency, and chronic vitamin B12 repletion at the time of vaccination. (ECF No. 123, p. 43.)

18

To the extent that Dr. Kedl had previously raised many of these conditions as predisposing petitioner to

inflammation (Ex. A, p. 9; Ex. C, p. 3), this reasoning would not defeat petitioner’s claim absent some

indication that these conditions are causes of GBS in themselves. A predisposition to inflammation is not

incompatible with vaccine causation. Petitioner’s burden is to prove that his vaccination was a substantial

contributing factor, not that his vaccination was the sole or predominant cause of his condition.

Accordingly, even if petitioner’s pre-existing conditions had operated in conjunction with his vaccination to

cause his GBS, petitioner could still meet his burden under the second Althen prong. See Shyface, 165

F.3d at 1352-53.

34

this case is unreliable. (ECF No. 123, pp. 39-40.) He contends that this is not rooted in

the experts’ theory of causation relative to the Prevnar vaccine and that it is

inappropriate for a claimant to “piggyback” on Table injury requirements. (Id.)

Schonberger et al. conducted an epidemiologic study that evaluated over 1,000

individuals who were diagnosed with GBS between October 1, 1976, and January 31,

1977. (Schonberger et al., supra, at Ex. 162, p. 5.) The authors found that fifty-two

percent of vaccinated cases included an onset of within one-to-two weeks following

vaccination. (Schonberger et al., supra, at Ex. 162, pp. 6, 8 fig.4.) That percentage

increased to seventy-one percent within four weeks following vaccination. (Id.)

Although respondent is correct to note that this case involves a different vaccine, the

1976 Swine flu vaccine is the only vaccination for which there is robust epidemiologic

data. Therefore, the post-Swine flu vaccine findings have been a significant

consideration assessing risk periods to be examined when studying other possible

causes of GBS. (E.g., Roger Baxter et al., Lack of Association of Guillain-Barré

Syndrome with Vaccinations, 57 CLINICAL INFECTIOUS DISEASES 197 (2015) (Ex. E, Tab

6) (using a 6-week interval for studying multiple vaccines and GBS based on the swine

flu vaccine findings).) As a general matter, Baxter et al. observed that, to the extent

GBS is generally accepted as a post-infectious autoimmune process, “most published

case series report that approximately two-thirds of all cases [of GBS] are preceded by a

gastrointestinal or respiratory infection within the prior 3 months.” (Id. at 1.) Regarding

molecular mimicry specifically, the IOM indicates that prior study has shown C. jejuni

infection precedes GBS by a “few weeks” in about a quarter of patients. (IOM 2012

Report, supra, at Ex. E, Tab 12, p. 11.) A mouse model used in examining molecular

mimicry as a cause of GBS found that it took two or more weeks for an injection of anti-

GM1 IgG to result in limb weakness. (Yuki et al., supra, at Ex. A, Tab 27, pp. 4-5.)

Thus, even setting the Schonberger et al. findings aside, there is still evidence to

support the general proposition that molecular mimicry can lead to clinically apparent

demyelination, and GBS specifically, over the course of several weeks. Special

masters have generally recognized eight weeks as the appropriate timeframe for onset

of GBS. E.g., Pierson, 2022 WL 322836, at 32-38; Barone, 2014 WL 6834557, at *12-

13.

Accordingly, petitioner has preponderantly demonstrated a medically acceptable

timeframe to infer causation and satisfied his burden under the third Althen prong.

d. Factor unrelated

Once petitioner has satisfied his own burden of proof, the burden shifts to

respondent to demonstrate by a preponderance of the evidence that the injury was

caused by factors unrelated to vaccination. § 300aa-13(a)(1)(B); Deribeaux ex rel.

Deribeaux v. Sec’y of Health & Human Servs., 717 F.3d 1363, 1367-69 (Fed. Cir. 2013).

In this case, respondent has not offered any other fact as a potential cause of

petitioner’s GBS. (See ECF No. 123, pp. 43-45.)

35

VI. Conclusion

After weighing the evidence of record within the context of this program, I find by

preponderant evidence that petitioner suffered GBS caused-in-fact by the Prevnar 13

vaccination he received on July 13, 2016. A separate damages order will be issued.

IT IS SO ORDERED.

s/Daniel T. Horner

Daniel T. Horner

Special Master

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