“We generally presume that a special master considered the relevant record evidence even though he does not explicitly reference such evidence in his decision.”
How later courts described this case
- “We generally presume that a special master considered the relevant record evidence even though he does not explicitly reference such evidence in his decision.”
- “Finding certain information not relevant does not lead to—and likely undermines—the conclusion that it was not considered.”
- denying Petitioner’s motion for review and noting that a possible causal link was not sufficient to meet the preponderance standard
- “[w]ithout more, [a] proximate temporal relationship will not support a finding of causation”
Written by the judges who cited it.
The opinion
In the United States Court of Federal Claims
OFFICE OF SPECIAL MASTERS
Filed: March 25, 2026
* * * * * * * * * * * * * * *
GUSTAVO VEGA, *
*
Petitioner, * No. 21-1794V
*
v. * Special Master Young
*
SECRETARY OF HEALTH *
AND HUMAN SERVICES, *
*
Respondent. *
* * * * * * * * * * * * * * *
Laura Levenberg, Muller Brazil, Dresher, PA, for Petitioner.
Debra A. Filteau Begley, United States Department of Justice, Washington, DC, for Respondent.
DECISION ON ENTITLEMENT1
On September 2, 2021, Gustavo Vega (“Petitioner”) filed a petition for compensation in
the National Vaccine Injury Compensation Program (“the Program”).2 Pet., ECF No. 1. Petitioner
alleged that he suffered from “Guillain-Barré Syndrome (“GBS”) an off-table cause-in-fact injury,
resulting from adverse effects of the human papillomavirus (“HPV”) vaccination” he received on
January 14, 2020. Id.
A careful analysis and weighing of all the evidence and testimony presented in this case in
accordance with the applicable legal standards3 reveals that Petitioner has failed to provide
1
Because this Decision 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 Decision 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
National Childhood Vaccine Injury Act of 1986, Pub L. No. 99-660, 100 Stat. 3755 (“the Vaccine Act”
or “Act”). Hereinafter, for ease of citation, all “§” references to the Vaccine Act will be to the pertinent
subparagraph of 42 U.S.C. § 300aa (2018).
3
While I have reviewed all of the information filed in this case, only those filings and records that are
most relevant to the decision will be discussed. Moriarty v. Sec’y of Health & Hum. 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.”) (citation omitted);
1
preponderant evidence that the HPV vaccine he received on January 14, 2020, caused him to
develop GBS. Accordingly, Petitioner is not entitled to an award of compensation.
I. Procedural History
Petitioner filed his petition, a declaration, and medical records on September 2, 2021. Pet.;
Pet’r’s Exs. 1–7, ECF No. 1. Petitioner filed additional medical records on October 15, 2021, and
June 16, 2022. Pet’r’s Ex. 9, ECF No. 13; Pet’r’s Exs. 10–11, ECF No. 20. On January 9, 2023,
Respondent filed his Rule 4(c) report arguing against compensation. ECF No. 24.
On April 3, 2023, Petitioner filed an expert report from Joseph Jeret, M.D. Pet’r’s Ex. 12,
ECF No. 27. Petitioner filed additional medical records on April 18, 2023, and May 16, 2023.
Pet’r’s Ex. 27, ECF No. 34; Pet’r’s Ex. 68, ECF No. 36. On April 20, 2023, Petitioner filed an
expert report from Omid Akbari, Ph.D. Pet’r’s Ex. 28, ECF No. 35. Respondent filed an expert
report from Andrew MacGinnitie, M.D., Ph.D., on August 28, 2023, and an expert report from
Matthew Brier, M.D., Ph.D., on October 6, 2023. Resp’t’s Ex. A, ECF No. 39; Resp’t’s Ex. C,
ECF No. 41. On December 15, 2023, Petitioner filed supplemental reports from Dr. Jeret and Dr.
Akbari. Pet’r’s Ex. 69–70, ECF No. 42. On March 26, 2024, Respondent filed supplemental reports
from Dr. Brier and Dr. MacGinnitie. Resp’t’s Exs. E–F, ECF No. 46. Petitioner filed a second
supplemental report from Dr. Jeret on April 9, 2024. Pet’r’s Ex. 86, ECF No. 48. That same day,
Petitioner filed a status report indicating he did not intend to file additional expert reports. ECF
No. 49.
The parties agreed to resolve entitlement with a ruling on the record. Informal Comm.,
docketed Apr. 25, 2024. On June 24, 2024, Petitioner filed a motion for a ruling on the record.
Pet’r’s Mot., ECF No. 51. Respondent filed a response on September 19, 2024, and Petitioner filed
a reply on October 21, 2024. Resp’t’s Response, ECF No. 54; Pet’r’s Reply, ECF No. 55.
This matter is now ripe for consideration.
II. Factual Background
A. Medical History
Petitioner’s pre-vaccination medical history included two prior craniotomies for excision
of an acoustic neuroma that left him with mild left-sided facial paralysis and left-sided hearing loss
and tinnitus. See Pet’r’s Ex. 3 at 49. On December 11, 2019, Petitioner saw his primary care
provider (“PCP”) where he received his first HPV vaccine but declined a flu vaccine. Pet’r’s Ex.
2 at 42, 44.
On January 14, 2020, Petitioner returned to his PCP for possible side-effects of flushing
and back pain since starting a new medication.4 Pet’r’s Ex. 2 at 10–11. The medication was
see also Paterek v. Sec’y of Health & Hum. 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.”).
4
The medication is not relevant to the issue here.
2
discontinued. Id. At this visit, Petitioner received his second HPV vaccine, at issue here, and he
again declined a flu vaccine. Id. at 11.
Eleven days later, on January 25, 2020, Petitioner presented to the emergency department
(“ED”) for the inability to bear weight on both his legs and “trouble gripping with both hands”
since 7:00am the day before. Pet’r’s Ex. 3 at 58. He reported that he first noticed his symptoms
when attempting to squeeze a tube of toothpaste; he also had difficulty typing on a keyboard. Id.
at 59. That morning, he woke up with his legs feeling “heavy” and weak. Id. The problem was
described as “gradually worsening.” Id. Petitioner further reported a recent upper respiratory tract
infection. Id. at 62. Neurological examination was positive for weakness. Id. at 60. He was
“[u]nable to hold the ‘okay’ sign” and “unable to rapidly tap fingers.” Id. at 61. He also had
decreased grip strength and ankle flexion.5 Id. at 61–62. GBS was suspected, and Petitioner was
admitted for further evaluation and treatment. Id. at 51, 62.
Following his January 26, 2020 admission, Petitioner was evaluated by neurologists Kristie
Bauman and Valeriya Levitan. Pet’r’s Ex. 3 at 77. His documented history included a recent HPV
vaccination and a cold in December, although a separate note from Dr. Levitan stated that
Petitioner had “no preceding illness.” Id. at 77–78. On examination, Petitioner demonstrated
weakness in his upper and lower extremities, absent reflexes at his biceps and triceps, and reduced
reflexes in his legs. Id. at 79. His sensation was largely intact except for a small area of numbness
on his left foot, and “mildly decreased” vibration sense in his bilateral toes. Id. His gait was
abnormal. Id. Drs. Bauman and Levitan concluded that Petitioner’s symptoms were most
consistent with GBS, although his “gait instability [was] out of proportion to his weakness and
reported sensory loss.” Id. at 80. Ganglioside antibody and other testing was ordered, and a five-
day course of intravenous immunoglobulin (“IVIG”) was started. Id. at 81.
A lumbar puncture on January 29, 2020, revealed elevated protein of 49 mg/dl (normal 15-
40 mf/dL), and ganglioside antibody testing revealed elevated GM1 and GD1a. Pet’r’s Ex. 3 at
153, 155, 172. These results confirmed a diagnosis of GBS. Id. On January 30, 2020, following
five IVIG treatments, Petitioner was discharged to inpatient rehabilitation. Id. at 51–57, 110.
Petitioner’s weakness plateaued while hospitalized but remained severe. Id. at 53. He struggled to
walk and complained of pain in his legs and lower back. Id.
Petitioner remained at the rehabilitation facility for 48 days, until March 20, 2020. Pet’r’s
Ex. 11 at 7–15. At discharge, he could walk with a rolling walker and while wearing bilateral
ankle-foot orthoses (“AFOs”), but he still required assistance with stairs and many activities of
daily living. Id. at 10. Outpatient physical therapy (“PT”) and occupational therapy (“OT”) were
recommended. Id. at 10, 297. Outpatient psychiatric therapy for significant anxiety and depression
was also recommended. Id. at 323–34.
After discharge from the inpatient rehab facility on April 17, 2020, Petitioner presented to
neurologist Dr. Elina Zakin. Pet’r’s Ex. 4 at 1. His history of present illness stated Petitioner had
a “recent admission for acute onset weakness of distal > proximal LE > UE in Jan[uary] 2020,
diagnosed with [acute inflammatory demyelinating polyneuropathy (“AIDP”)] (in the setting of
5
Petitioner also exhibited a left-sided facial droop, which was his “baseline” caused by prior removal of
an acoustic neuroma. Pet’r’s Ex. 3 at 58, 61.
3
recent HPV vaccination) who presents to establish care for AIDP.” Id. He reported that prior to
vaccination, he was healthy and running. Id. at 2. Two days after the hepatitis and HPV
vaccinations, he “started to experience sudden onset weakness of finger flexors.” Id. At this visit
Petitioner still had complaints of weakness and noted increased drooling with the onset of GBS
symptoms. Id. at 2–3. Dr. Zakin explained that Petitioner likely had the acute motor axonal
neuropathy (“AMAN”) variant of GBS, given his predominant motor weakness in his distal
muscles with no sensory abnormalities. Id. at 4. Dr. Zakin recommended an electromyogram/nerve
conduction study (“EMG/NCS”), and told Petitioner to continue his home exercise program. Id.
On May 7, 2020, Petitioner presented to NYU Medical Center for an initial outpatient PT
evaluation. Pet’r’s Ex. 4 at 29. Petitioner subsequently completed 50 physical therapy sessions
through April 1, 2021. See id. at 29–116; Pet. Ex. 3 at 389–736.
On June 26, 2020, Petitioner presented to Dr. Zakin for a follow-up visit. Petitioner
complained of continued numbness and tingling in his hands and feet. Pet’r’s Ex. 4 at 117.
Petitioner underwent an EMG, which showed “changes consistent with an acquired motor
axonopathy or neuronopathy predominantly involving the lower extremities, with sparing of
sensory nerve involvement.” Id. at 121. The EMG also showed evidence of ongoing severe axonal
denervation. Id.
Petitioner returned to Dr. Zakin on September 2, 2020. Pet’r’s Ex. 4 at 189. He was still
taking Gabapentin for his pain. Id. He had undergone an EMG of his face in August 2020, and it
revealed a chronic partial and inactive left facial neuropathy. Id. at 193. Dr. Zakin further explained
that Petitioner had “residual left facial palsy” from his prior brain surgeries. Id. Dr. Zakin noted
Petitioner was improving, more stable, and his gait normal, although he continued to rely on a
walker. Id. Continued PT was recommended. Id.
During a follow-up virtual visit with Dr. Zakin on October 15, 2020, Dr. Zakin discussed
with Petitioner his “very slow course of improvement,” which was “expected in motor variants of
GBS.” Pet’r’s Ex. 4 at 249. Dr. Zakin ordered monthly IVIG treatments for three months. Id.
Petitioner underwent IVIG infusions in December 2020, January 2021, and February 2021. Id. at
361, 398, 429. On February 22, 2021, Petitioner reported a slight improvement in his balance when
he spoke with Dr. Zakin. Id. at 429. Dr. Zakin recommended additional IVIG over the next four
months and continued adherence to home exercises. Id. at 434, 459.
On July 12, 2021, Petitioner had a televisit with Dr. Zakin. Pet’r’s Ex. 8 at 509. He reported
continued improvement and that he kept up with PT during the Spring of 2021. Id. He still used
AFOs and a rolling walker, and he reported severe foot pain after walking for more than one hour.
Id. Dr. Zakin noted improved balance and recommended continued aggressive performance of his
home exercises. Id. at 512–13.
Petitioner saw Dr. Zakin on January 27, 2022, and he asked a number of questions about
his prognosis. Pet’r’s Ex. 68 at 12. He felt his strength was stable, that his ankle and foot strength
had improved, but that he sometimes dropped objects unexpectedly. Id. He also reported episodic
blurred vision, intermittent palpitations and shortness of breath, insomnia, right knee pain, and he
wanted to discuss whether he should return to his prior “high stress” job. Id. Petitioner expressed
4
concern over getting the COVID vaccine for “heightened auto-immunity.” Id. He also stated that
he was still taking gabapentin at night for neuropathic pain. Id. Examination documented mildly
reduced strength in his bilateral lower extremities and a tremor in his upper extremities. Id. at 15.
Petitioner still demonstrated left-sided facial weakness. Id. His reflexes were normal throughout,
and sensory testing was normal, except for a “small patch of numbness to all modalities at medial
ankle on the left.” Id. He could rise spontaneously from a chair, and while his gait was improved,
it was wide-based and he held onto a walker. Id. at 16. Dr. Zakin explained that many of his
questions concerned symptoms that were not neurologic, and she referred him for an eye
examination, recommended he discuss anxiety with his counselor, and ordered a brace for
Petitioner’s knee. Id. at 17–18. She stated that Petitioner was improving, and ordered additional
PT. Id.
III. Experts
A. Expert Qualifications
1. Petitioner’s Expert, Dr. Omid Akbari, Ph.D.
Dr. Akbari is an immunologist. Pet’r’s Ex. 28 at 1. He received his Ph.D. in cellular and
molecular immunology from the National Institute of Medical Research in London, United
Kingdom, and completed a postdoctoral fellowship at Stanford University. Pet’r’s Ex. 29 at 1. He
is currently a Professor of Immunology at Keck School of Medicine, University of Southern
California. Pet’r’s Ex. 28 at 1. His research is “focused on the role of immune tolerance and how
immune cells induce autoimmune and allergic diseases.” Id. In his laboratory “there are multiple
research studies which are relevant to the issue of understanding the medical theories involved in
regard to how a vaccination can result in an appropriate or dysregulated immune responses causing
inflammation.” Id. “The known mechanisms of pathogenesis involved in these injuries involve the
same mechanisms and cellular pathways that are investigated in [his] laboratory.” Id. Dr. Akbari
serves as an editor and reviewer for several journals and has numerous publications. Id.; Pet’r’s
Ex. 29 at 5, 9–16.
2. Petitioner’s Expert, Dr. Joseph Jeret, M.D.
Dr. Jeret is a board-certified neurologist. Pet’r’s Ex. 12 at 1. He received his M.D. from
SUNY Downstate Medical Center where he subsequently completed a neurology residency and a
fellowship in clinical neurophysiology. Id.; Pet’r’s Ex. 13 at 1. He is employed by Optumas as a
physician in the neurology department and on staff at South Nassau Community Hospital and
Mercy Medical Center. Pet’r’s Ex. 12 at 1. He also maintains a neurology practice. Id. He
“routinely care[s] for patients with varied neurologic illnesses, including spine disease and nerve
disease. It is not uncommon for [his] patients to have complex clinical presentations and multiple
diagnoses. Specifically, [he has] diagnosed patients with GBS, CIDP, and other peripheral nerve
disorders.” Id. Dr. Jeret has extensive publications in neurology. Pet’r’s Ex. 13 at 2–7.
5
3. Respondent’s Expert, Andrew MacGinnitie, M.D., Ph.D.
Dr. MacGinnitie is board certified in allergy/immunology and pediatrics. Resp’t’s Ex. A at
2. He received his Ph.D. in pathology and his M.D. from the University of Chicago Pritzker School
of Medicine. Id. at 1. Thereafter, he completed a pediatrics residency and an allergy/immunology
fellowship at Boston Children’s Hospital. Id. at 1–2. He is currently an Attending Physician as
well as the Clinical Chief for the Division of Immunology at Boston Children’s Hospital. Id. at 1.
He does “not routinely care for patients with GBS except when they have concurrent allergic
and/or immunologic issues.” Id. at 2. Dr. MacGinnitie has published numerous articles. Resp’t’s
Ex. B at 12–18.
4. Respondent’s Expert, Matthew Brier, M.D., Ph.D.
Dr. Brier is a board-certified neurologist. Resp’t’s Ex. D at 3. He received his Ph.D. in
neuroscience and his M.D. from Washington University in St. Louis. Id. at 1; Resp’t’s Ex. C at 1.
Thereafter, he completed a fellowship in multiple sclerosis and neuroimmunology as well as a
residency at Washington University. Resp’t’s Ex. C at 1. He is currently an Assistant Professor of
Neurology and Radiology at Washington University and an Attending Neurologist at Barnes
Jewish Hospital. Id. He cares for patients with immunologic and autoimmune disorders of the
nervous system as well as patients with general neurology conditions, including GBS “and its
mimics.” Id. He has published numerous articles. Resp’t’s Ex. D at 6–12.
B. Expert Reports
1. Dr. Akbari’s First Report6
Dr. Akbari spent much of his first report overviewing the immune system. Pet’r’s Ex. 28
at 7–12. He summarized:
[T]he main functions of the immune system are to recognize and subsequently
eliminate foreign antigens, to induce immunologic memory, and to develop
tolerance to self-antigens. Effective immunologic homeostasis relies on a continual
balance among several factors, including T helper cell activation and suppression
by regulatory T cells. Innate like lymphocytes are fast acting immune cells that may
react to foreign stimuli such as vaccines. When homeostasis is disrupted and the
6
Dr. Akbari spent much of his first report discussing vaccines not relevant to this petition. See, e.g.,
Ex. 28 at 5 (“My research into your particular question concluded that the theory of molecular mimicry
supports that Tdap vaccination can plausibly cause an adverse immune cross reaction and result in the
onset of GBS.”), 7 (“Tdap . . . causes a local inflammatory reaction.”), 16 (“A second criterion for
implicating molecular mimicry. . . is to demonstrate the plausibility of cross-reactivity by autoreactive T-
cells or autoantibodies with a microbial antigen, or in this case to a component of the Tdap vaccine.”), 18
(“[T]he role of Treg/Teff after immunization with flu and also the role of Tregs in controlling unwanted
immune response are well established.”), 20 (discussing B and T cell responses to tetanus toxoid), 20-21
(referring to “the potential for crossreactivity from tetanus toxoid to self-peptides in some people”).
Because Dr. Akbari did not compare the Tdap and flu vaccines to the HPV vaccine, I will not elaborate
on these opinions further.
6
immune system responds in favor of activation, as it would when you stimulate it
with a vaccine, the host becomes susceptible to autoimmunity. In GBS, research
indicates that this balance is being disrupted leaving the host susceptible to an
adverse autoimmune reaction upon stimulation of the immune system from
infection or vaccination, mediated by activation of inflammasome.
Id. at 10.
Dr. Akbari proposed the theory of molecular mimicry to explain how the HPV vaccine can
cause GBS. Pet’r’s Ex. 28 at 5, 12–15. He explained molecular mimicry is “the mechanism by
which an immune stimulated response by infection or other method, i.e. vaccination, can trigger
cross-reactive antibodies or T cells that cause the symptoms of autoimmune disease.” Id. at 6.
“One important criterion that can implicate molecular mimicry as a causal mechanism is
the identification of T cells or antibodies in patients with the disease.” Pet’r’s Ex. 28 at 15. “Current
research indicates that autoimmunity in GBS is most likely mediated by antibodies directed against
myelin antigens, along with autoreactive T cells and macrophages that invade the myelin sheath,
axonal membranes, and/or the nodes of Ranvier.” Id. According to Dr. Akbari, GBS patients “have
increased levels of pathogenic autoreactive T cells and antibodies present in the peripheral blood
and cerebral spinal fluid [(“CSF”)].” Id. “Antibodies against gangliosides have been found in the
serum of GBS patients during the acute phase of the disease.” Id. (citing Pet’r’s Ex. 54;7 Pet’r’s
Ex. 55).8 “Anti-glycan antibodies directed against gangliosides are considered a major immune
effector which can induce damage to intact nerve fibers and are considered to be a major
contributor in the pathogenesis of GBS.” Id. (citing Pet’r’s Ex. 54).
Dr. Akbari also raised regulatory T-cell dysfunction, inflammasome activation secondary
to vaccine adjuvants, and a combination of these with molecular mimicry as mechanisms of
causation. See generally Pet’r’s Ex. 28. He opined that “[r]egulatory T cells play an important role
in induction of GBS after vaccination.” Id. at 17. “HPV vaccine is shown to stimulate the
[regulatory T cells] and [effector T cells] in normal individuals after immunization. However, in
some individuals, after vaccination, pathogenic [effector T cells] cells are able to differentiate
further, exert robust effector function and cause severe injury such as GBS.” Id. at 18. Dr. Akbari
also argued that adjuvants, including aluminum, “facilitate the induction of immune responses
mainly by triggering pathways such as inflammasome.” Id. at 9.
Specific to the HPV vaccine causing GBS, Dr. Akbari cited several articles to show an
association. Pet’r’s Ex. 28 at 19–20. Miranda et al.9 was a cohort study designed to evaluate
whether HPV vaccination could induce or trigger autoimmune diseases. Pet’r’s Ex. 63 at 1. Over
two million girls aged 13–16 years were included in the study and followed over four years using
French nationwide databases. Id. Among the 2,252,716 girls, 37% received an HPV vaccine and
7
Gang Zhang et al., Erythropoietin Enhances Nerve Repair in Anti-Ganglioside Antibody-Mediated
Models of Immune Neuropathy, 6 PLOS ONE e27067 (2011).
8
Hugh J. Willison & Nobuhiro Yuki, Peripheral Neuropathies and Anti-Glycolipid Antibodies, 125
BRAIN 2591 (2002).
9
Sara Miranda et al., Human Papillomavirus Vaccination and Risk of Autoimmune Diseases: A Large
Cohort Study of over 2 Million Young Girls in France, 35 VACCINE 4761 (2017).
7
4,096 autoimmune diseases occurred during a mean follow-up time of 33 months. Id. Forty-three
of the autoimmune diseases identified were GBS. Id. at 4. The authors concluded that there was
not an increased risk of autoimmune disease after HPV vaccination except for GBS. Id. at 1, 4, 6.
The association between HPV vaccination and GBS was “particularly marked in the first [two]
months following vaccination.” Id. at 4. “This association did not differ with the type of HPV
vaccine or whether or not GBS was preceded by a recent history of gastrointestinal or respiratory
tract infection.”10 Id.
Souayah et al.11 used data from the Vaccine Adverse Event Reporting System (“VAERS”)
to identify 69 cases of GBS within six weeks of HPV vaccination. Pet’r’s Ex. 64 at 1. The authors
did not draw a conclusion as to causation and suggested further surveillance is warranted. Id. at 1,
4. Boender et al.12 reviewed 25 studies and found that “[i]n 22 studies, no increased risk of GBS
was observed, while in three studies a “signal of increased risk of GBS after HPV vaccination was
identified.” Pet’r’s Ex. 16 at 1. The authors concluded: “The absolute and relative risk of GBS
after HPV vaccination is very low and lacks statistical significance.” Id. Dr. Akbari then cited a
Centers for Disease Control and Prevention (“CDC”) report13 that found between December 2014
and December 2017, “when approximately 28 million doses of Gardasil had been given out in the
United States, there were [four] confirmed reports of GBS.” Pet’r’s Ex. 28 at 19.
Dr. Akbari further opined that host susceptibility “is a significant factor the development
of autoimmune disease, including neuropathy such as GBS, independent of the initiating
pathologic cause.” Pet’r’s Ex. 28 at 20. “[T]he decreased number of T regulatory cells most likely
is a main factor resulting in a person’s predisposition to develop autoimmune diseases after
immunization.” Id.
In the conclusion section of his first report, Dr. Akbari raised the mechanism of prime and
recall response to help demonstrate a logical sequence of cause and effect. Pet’r’s Ex. 28 at 22. He
wrote that “if the same stimuli [that are produced in the first dose a vaccine] such as the second
dose of vaccine are given a few weeks to a few months after the initial dose, the memory cells
begin to replicate and produce cytokines in a significantly short period of time.” Id. Dr. Akbari
explained that as a result of this “secondary exposure to a given antigen triggers an immune
response that is more vigorous and robust often resulting in the onset of demyelinating disease and
GBS.” Id. Thus, Dr. Akbari concluded that, “the timing between receipt of the second vaccine [the
one subject to this petition] and development of demyelinating disease is approximately 11 days,
which is an appropriate timeframe for the immune-mediated mechanism of causing neuropathy.”
Id.
10
Over half of the HPV vaccine GBS group also had an infection (a gastrointestinal or respiratory illness)
that preceded that onset of GBS, and over half of those cases occurred more than six months after
vaccination. Pet’r’s Ex. 63 at 5 tbls. 4–5.
11
Nizar Souayah et al., Guillain-Barré Syndrome After Gardasil Vaccination: Data from Vaccine Adverse
Event Reporting System 2006-2009, 29 VACCINE 886 (2011).
12
T. Sonia Boender et al., Risk of Guillain-Barré Syndrome After Vaccination Against Human
Papillomavirus: A Systemic Review and Meta-Analysis, 1 January 2000 to 4 April 2020, 27 EURO
SURVEILLANCE (2022).
13
This CDC report was not filed as an exhibit.
8
2. Dr. Jeret’s First Report
Dr. Jeret opined Petitioner’s GBS developed 10 days after his second HPV vaccination.
Pet’r’s Ex. 12 at 7. He explained that vaccines “stimulate the body’s immune system to create
antibodies,” but on rare occasions, it “‘gets the wrong message’ and will attack an unintended
target by creating an autoimmune response against peripheral nerve myelin.” Id. at 8. Dr. Jeret
explained this is called molecular mimicry and “is the basis for GBS after flu and other vaccines.”
Id. at 8, 10. “The same molecular mimicry is the basis for GBS after HPV vaccine. Vaccines like
Gardasil may be more likely to trigger GBS because of the high antigenicity of the vaccine’s
recombinant proteins and other components of the vaccine.” Id. at 8.
Dr. Jeret relied on the World Health Organization (“WHO”) causality assessment criteria
in Collet et al.14 to conclude that it is “very likely/certain that [Petitioner’s] HPV vaccine caused
his GBS” because the “clinical event occurred with a plausible relationship subsequent to vaccine
administration” and there was “no concomitant disease or drug that [could] explain his
development of GBS.” Pet’r’s Ex. 12 at 10 (citing Pet’r’s Ex. 17 at 3 tbl. 2). The criteria for
causation used in Collet et al. consists of (1) biological plausibility, (2) “time elapsed between the
vaccine administration and the onset of the adverse events,” and (3) “whether other factors (drugs,
chemicals[,] or underlying disease) could account for the adverse symptoms.”15 Pet’r’s Ex. 17 at
1. In Petitioner’s case, Dr. Jeret believed there “was no preceding viral or bacterial illness that
were recognized triggers.” Pet’r’s Ex. 12 at 10. While he opined that C. jejuni is “probably the
most clearly-defined illness that precipitates GBS,” trivial upper respiratory infections (“URIs”)
are not listed as triggers for GBS. Id. at 9 (citing Pet’r’s Ex. 18).16 “Thus, [Petitioner’s] preceding
URI—whose timing is not specified, whose associated symptoms are not specified, and which is
never diagnosed as influenza or considered by any of the practitioners to have been significant—
did not play a role in his subsequent development of GBS.” Id. Like Dr. Akbari, Dr. Jeret cited
Miranda et al. and Souayah et al. for identifying cases of GBS after HPV vaccination. Pet’r’s Ex.
12 at 8. Dr. Jeret also commented that he did not believe that Petitioner’s medications played any
role in the development of his GBS. Id. at 7.
Dr. Jeret opined that “GBS beginning 3–42 days after the vaccine would be consistent with
a causal relationship based on molecular mimicry,” and reiterated Petitioner’s GBS began 10 days
after vaccination. Pet’r’s Ex. 12 at 11.
14
J.P. Collet et al., Monitoring Signals for Vaccine Safety: The Assessment of Individual Adverse Event
Reports by an Expert Advisory Committee, 78 BULLETIN OF THE WORLD HEALTH ORGANIZATION 178
(2000).
15
This is not the standard used in the Vaccine Program.
16
Marinos C. Dalakas, Guillain-Barré Syndrome: The First Documented COVID-19-Triggered
Autoimmune Neurologic Diseases, 7 NEUROLOGY: NEUROIMMUNOLOGY & NEUROINFLAMMATION 781
(2020). Dr. Jeret also cited a GBS fact sheet from Yale Medicine online; however, this was not filed as an
exhibit.
9
3. Dr. MacGinnitie’s First Report
Dr. MacGinnitie agreed that GBS is the proper diagnosis, but he disagreed that the HPV
vaccine was the cause. See generally Resp’t’s Ex. A. He also agreed that molecular mimicry can
be a trigger for autoimmune disease and cited Peterson & Fujinami17 for criteria. Id. (citing
Resp’t’s Ex. A, Tab 1).
Resp’t’s Ex. A, Tab 1 at 6 tbl. 3.2. While Dr. MacGinnitie opined these criteria do not need to be
satisfied in every case, he noted Petitioner, through Dr. Jeret and Dr. Akbari, did not provide
“evidence that fulfills any of these criteria.” Resp’t’s Ex. A at 8.
In addressing the first criterion, Dr. MacGinnitie opined that GBS “can be caused by the
generation of antibodies against carbohydrate antigens expressed by the bacteria C. jejuni, which
also recognize similar molecules called gangliosides on human nerve axons.” Resp’t’s Ex. A at 8.
“These antibodies then mediate damage to the nerve cells resulting in GBS symptoms.” Id. He
noted that Petitioner tested positive for two gangliosides, GM1 and GD1a, and that the latter is
associated with GBS. Id. (citing Pet’r’s Ex. 3 at 155–56). However, he opined that Gardasil does
not contain any carbohydrates that could be cross-reactive with human gangliosides. Id. at 9. He
explained that Gardasil contains the L1 proteins of different HPV serotypes produced in yeast. Id.
(citing Resp’t’s Ex. A, Tab 5 (Gardasil package insert); Resp’t’s Ex. A, Tab 6)).18 “These L1
proteins spontaneously self-assemble into multimers, termed virus-like particles (VLPs) which are
subsequently purified, removing any contaminating yeast material. Thus, the resulting vaccine
should not contain any components that would cross react with gangliosides.” Id. “Without any
vaccine component cross-reactive with human gangliosides, there is no evidence that molecular
mimicry between vaccine components and gangliosides could have resulted in [Petitioner’s] GBS
nor his positive testing for anti-ganglioside antibodies.” Id.
Next, Dr. MacGinnitie opined there is no evidence of cross-reactive antibodies or T-cells
in this case. Resp’t’s Ex. A at 9. Similarly, he opined there is no animal model linking the HPV
vaccine to GBS. Id. Lastly, he found no large scale, population-based studies supporting HPV
vaccination as a trigger for GBS. Id. Dr. MacGinnitie concluded that “[i]n the absence of even a
single criteria being fulfilled, any immune stimulus (infections, exposure to allergen, vaccination)
17
Lisa K. Peterson & Robert S. Fujinami, Molecular Mimicry in AUTOANTIBODIES 13 (2nd ed., Elsevier
2007).
18
Rashi Yadav et al., Virus-Like Particle-Based L2 Vaccines Against HPVs: Where Are We Today?, 12
VIRUSES 18 (2020).
10
could be hypothesized to trigger any autoimmune disease.” Id. at 11. Dr. MacGinnitie further
criticized the literature cited by Dr. Akbari and Dr. Jeret. Id. at 9–11. He described reliance on
VAERS as “problematic” because it is based on active reporting with no controls or auditing
process to verify diagnosis. Id. at 10. Next, Dr. MacGinnitie argued that the Boender et al. and Gee
et al.19 articles found “no conclusion can be drawn about an increased or decreased risk of GBS
post-vaccination,” and that there is “no evidence of an increased risk of GBS following 4vHPV,”
respectively. Id. (first citing Pet’r’s Ex. 16, then quoting Pet’r’s Ex. 20 at 1) Dr. MacGinnitie
acknowledged that the Miranda et al. study “did find an increased rate of GBS in the [two] months
after vaccination, but [he noted that] this was a relatively small study.” Id. Dr. MacGinnitie further
noted that this finding could not be replicated in larger, epidemiologic studies, and it “was included
in the meta-analysis by Boender et al. along with the negative studies and no statistically increased
overall risk was found.” Id. These studies, according to Dr. MacGinnitie, provide the best evidence
against causation. Id. However, given the rare occurrence of GBS, and the limits of epidemiology
detecting incidence rates in such small populations, Dr. MacGinnitie added that “it is impossible
to completely rule out a very small increased (or decreased) risk.” Id.
Dr. MacGinnitie found no basis for Dr. Akbari’s theories based on regulatory T-cell
dysfunction and inflammasome activation by aluminum adjuvants. Resp’t’s Ex. A at 12–14.
Indeed, he opined the aluminum adjuvant used in the Gardasil vaccine “is safe and actually
decreases systemic inflammation after vaccination.” Id. at 14 (citing Resp’t’s Ex. F, Tab 9).20
Moreover, Dr. MacGinnitie pointed out that Petitioner did not exhibit symptoms such as fever or
malaise in the days after vaccination that would be indicative of substantial system inflammation.
Id. at 13.
As to the URI, Dr. MacGinnitie believed that “[g]iven timing of [Petitioner’s] GBS with
onset in January, when influenza is widespread in the community, it is certainly possible that the
URI [Petitioner] reported to [the ED physician] was influenza and this was the trigger of his GBS,
given that influenza, unlike HPV, is a known trigger of GBS.” Resp’t’s Ex. A at 14. However, he
pointed out that many cases of GBS do not have an identified trigger. Id.
4. Dr. Brier’s First Report
Dr. Brier analyzed the citations cited by Petitioner’s experts and concluded they only show
that there exists “cases of GBS that may be temporally preceded by HPV vaccine.” Resp’t’s Ex.
C at 8. He referred to the WHO 2019 manual for “Causal Assessment of an Adverse Event
Following Immunization.”21 Id. at 9. According to Dr. Brier, the manual defines adverse events
following immunization as having two levels of scientific basis: population and individual. Id. He
highlighted the necessary criteria they use and their applicability to this case:
19
Julianne Gee et al., Risk of Guillain-Barré Syndrome Following Quadrivalent Human Papillomavirus
Vaccine in the Vaccine Saftey Datalink, 35 VACCINE 5756 (2017).
20
Harm HogenEsch, Mechanism of Immunopotentiation and Safety of Aluminum Adjuvants, 3 FRONTIERS
IMMUNOLOGY 406 (2013).
21
This was not filed as an exhibit.
11
Id. According to Dr. Brier, this precludes Petitioner’s GBS being caused by the HPV vaccine for
failure to meet these criteria. Id. Dr. Brier acknowledged that this is not the standard Petitioner
needs to meet here. Id. at 10. However, even without using these criteria, Dr. Brier “did not see
any reliable evidence in this case establishing, to a more likely than not standard, that the HPV
vaccine can cause GBS, or did cause [Petitioner’s] GBS.” Id. Dr. Brier believed Petitioner’s GBS
is idiopathic. Id.
5. Dr. Akbari’s Supplemental Report
In response to the critiques from Respondent’s experts, Dr. Akbari detailed more of his
molecular mimicry theory. See generally Pet’r’s Ex. 70. He “conducted an extensive analysis of
the sequences present in the Gardasil [v]accine” to “shed light on the specific molecular
components that might trigger molecular mimicry and, subsequently, the development of
autoimmune reactions.” Id. at 2. He conducted a BLAST search to “investigate potential molecular
mimics between the vaccine component and the [m]yelin basic protein [(“MBP”)].” Id. Dr. Akbari
cited Cornblath et al.22 for his opinion that MBP “plays a pivotal role as the main target in immune
attacks leading to GBS.”23 Id. (citing Pet’r’s Ex. 74). Cornblath et al. noted several studies had
been done measuring immunoreactive MBP (“iMBP”) in the CSF of patients with central nervous
system (“CNS”) disease and sought to determine iMBP levels in patients with peripheral
neuropathies, including GBS. Pet’r’s Ex. 74 at 1. The authors found that “MBP-like material is
present in the CSF of most patients with longstanding demyelinating polyradiculoneuropathies.”
Id. The question remained, what is the source of this material. Id. They hypothesized that “the
most likely source is P1 protein from [peripheral nervous system] myelin breakdown in the spinal
roots.” Id. Cornblath et al. compared their findings to studies of patients with CNS disease and
found that “[i]n patients with peripheral neuropathy, confusing findings may result.” Id. at 2. They
concluded that “there is no method of determining the origin of iMBP in CSF.” Id.
22
David R. Cornblath et al., Immunoreactive Myelin Basic Protein in Cerebrospinal Fluid of Patients
with Peripheral Neuropathies, 20 ANNALS NEUROLOGY 370 (1986).
23
Dr. Akbari wrote: “Please note that while GBS is indeed a complex disease with various antigens
involved, it’s worth highlighting that approximately 50 percent of GBS patients exhibit the presence of
antibodies against [MBP].” Pet’r’s Ex. 70 at 4 (citing Pet’r’s Ex. 74).
12
Dr. Akbari cited the Gardasil vaccine package insert to show the ingredients include
purified virus-like particles (“VLPs”) of the major capsid (L1) protein of HPV. Pet’r’s Ex. 70 at 2
(citing Pet’r’s Ex. 18). He explained that these “VLPs are purified, and an aluminum-containing
adjuvant is subsequently introduced to enhance the immune response.” Id. at 3. Dr. Akbari then
opined that HPV shares sequences that are “identical or highly similar with myelin proteins.” Id.
Dr. Akbari did not include his search parameters in his report but provided the following results:
Id. Dr. Akbari opined “there are five amino acids featuring three consecutive matches at critical
binding points, a phenomenon supported by studies indicating that such homology is adequate to
trigger molecular mimicry.” Id. He also found there are three amino acids whose similarity is
“tolerated.” Id. He relied on Hausman et al.24 to state “the replacement of asparagine (N) with
arginine (R) at position 94 is tolerated; in other words, these substitutions are recognized by a T
cell clone responsive to myelin basic protein, albeit with reduced potency.” Id. (citing Pet’r’s Ex.
73). “Furthermore, the isoleucine (I) to alanine (A) substitution at position 95 is well-tolerated,
providing us with a total of seven out of twelve consecutive amino acids featuring exact matches
or permissible substitutions. Remarkably, these substitutions still facilitate the stimulation of a
human T cell clone reactive to gangliosides.” Id. He stated the same is true for HPV type 18 L1,
with four amino acid identities to myelin basic protein. Id. at 3–4. He cited Gautam et al.25 to
explain the significance of seven out of 12 amino acid identities as well as the adequacy of five
out of 12 amino acid identities “to provoke an immune response directed at myelin basic protein”
and “to induce clinical demyelination.” Id. at 4 (citing Pet’r’s Ex. 76).
Dr. Akbari said the goal of this analysis was to “shed light on the scientific underpinnings
of how the HPV vaccine might influence the breakdown of tolerance to gangliosides and
potentially act as a trigger to induce GBS.” Pet’r’s Ex. 70 at 3. He concluded:
Based on an overwhelming preponderance of evidence, it is unequivocal that the
Gardasil vaccine was the predominant instigator of GBS in [Petitioner]. This
determination is unequivocally rooted in a scrupulously [sic] analysis of the
vaccine’s constituents and their compelling potential to incite grievous pathological
immune responses through the unequivocal mechanism of molecular mimicry.
24
Stefan Hausman et al., Structural Features of Autoreactive TCR That Determine the Degree of
Degeneracy in Peptide Recognition, 162 J. IMMUNOLOGY 338 (1999).
25
Anand M. Gautam et al., A Viral Peptide with Limited Homology to a Self Peptide Can Induce Clinical
Signs of Experimental Autoimmune Encephalomyelitis, 161 J. IMMUNOLOGY 60 (1998).
13
Id. at 6.
Next, Dr. Akbari addressed “the inquiries posed by Dr. MacGinnitie concerning the roles
of cytokines and the mechanisms through which molecular mimicry and the inflammasome
contribute to the process of demyelination.” Pet’r’s Ex. 70 at 8. He explained cytokines are
“signaling molecules within the immune system [that] play a pivotal role in orchestrating immunes
response” and “central players” for demyelination. Id. He said cytokines “can act as mediators in
the cascade of events that lead to the destruction of myelin,” which is characteristic of GBS. Id.
“For example, pro-inflammatory cytokines such as tumor necrosis factor-alpha (TNF-α) and
interleukin-1 beta (IL-1β) can contribute to the activation of immune cells and the subsequent
attack on myelin.” Id. “Moreover, the inflammasome, a complex of proteins responsible for
initiating an inflammatory response, can be closely linked to demyelination. It serves as a platform
for the activation of pro-inflammatory cytokines like IL-1β and IL-18, which further exacerbate
the immune response and can lead to tissue damage, including demyelination.” Id.
Dr. Akbari proposed that the “HPV vaccination is capable of inducing a robust
inflammasome activation, and the consequences include the production of active caspase-1,
converting inactive precursor cytokines of the IL-1 family (including IL-1a and IL-1b), to their
active forms.” Pet’r’s Ex. 70 at 9 (citing Pet’r’s Ex. 77).26 Dr. Akbari added that “[b]esides IL-1
and inflammasome, another vaccine-induced pro-inflammatory cytokine is IL-6. It is important to
also mention that Tregs are able to suppress inflammasome activation and actively regulate
proinflammatory cytokines, suggesting that impaired Tregs can also contribute to the induction of
demyelinating diseases.” Id. In support of this assertion, Dr. Akbari cited the Haas et al.27 article,
which took revelations discovered in prior studies regarding Treg dysfunction in multiple sclerosis
patients and sought to determine the cause for new treatments for that condition. Pet’r’s Ex. 81.
The authors found that “diminished suppressive Treg potencies in [multiple sclerosis] are related
to disequilibrium in the homeostatic composition of circulating Treg and most likely result from
an altered thymic release of newly formed T cells into the periphery.” Id. at 7. They were hopeful
“that pharmacologic modulation of the thymus and the reconstruction of peripheral Treg
homeostasis” could be a “promising treatment strategy in [multiple sclerosis] and other
autoimmune disorders.” Id. at 8. As to the applicability to GBS, Dr. Akbari suggested “that the
prevalence of newly generated regulatory T cells (Treg) is critical for Treg suppressive function
and determines Treg dysfunction in demyelinating disease.” Pet’r’s Ex. 70 at 9.
Specifically relevant to the HPV vaccine causing GBS, Dr. Akbari stated:
All we are asserting is that the HPV vaccine has the capability to cause GBS. As
demonstrated earlier, the combination of segments of the HPV virus and alum
adjuvant potentiates the effects of antigens, sometimes more than 100 times, and in
certain individuals, this combination can result in the development of GBS.
26
Virginie Petrilli et al., The Inflammasome: A Danger Sensing Complex Triggering Innate Immunity, 19
CURRENT OP. IMMUNOLOGY 615 (2007).
27
Jurgen Haas et al., Prevalence of Newly Generated Naïve Regulatory T Cells (Treg) is Critical for Treg
Suppressive Function and Determines Tred Dysfunction in Multiple Sclerosis, 179 J. IMMUNOLOGY 1322
(2007).
14
Pet’r’s Ex. 70 at 10. He again referenced Miranda et al., Souayah et al., and Boender et al. Id. at
11. Dr. Akbari argued that “[o]verall, these studies collectively suggest that HPV can potentially
lead to GBS.” Pet’r’s Ex. 70 at 11.
Lastly, Dr. Akbari again commented on his opinion that Petitioner developed GBS after
his second dose of the HPV vaccine. Pet’r’s Ex. 70 at 11–12, 16. He explained:
In [i]mmunology the requirement of a second (or possibly third or multiple) signal
to induce pathogenic disease is often essential. These requirements also explain
how molecular mimicry can facilitate both immune tolerance and immune
autoreactivity. Scientific theories are neither absolutely false nor absolutely true.
They are always somewhere in between. Some theories are better, more credible,
and more accepted than others, and that is why we always state “more likely than
not” or based on “preponderance of evidence.”
Id. at 16. He added that when a “subsequent stimulus, such as the second dose of a vaccine, is
administered a few weeks to a few months after the initial dose, these memory cells are awakened.
They begin to replicate and produce cytokines in significantly higher quantities.” Id. at 12.
According to Dr. Akbari, this “booster effect triggers a more vigorous and robust immune
response, which, in some cases, can lead to adverse effects like GBS.” Id. Dr. Akbari found this
important since Petitioner “did not experience any adverse effects after his first dose but developed
GBS 11 days after the second dose. This temporal relationship suggests that the HPV vaccination
could indeed be a contributing factor to the development of GBS in his case.” Id.
6. Dr. Jeret’s Supplemental Reports
Dr. Jeret filed two supplemental reports disagreeing with Dr. Brier. Pet’r’s Exs. 69, 86. He
focused on statistical issues with medical literature, particularly how GBS is rare and some cases
may go unreported. Pet’r’s Ex. 69 at 1–2. His opinion remained the same as his original report. Id.
at 2–3; Pet’r’s Ex. 86 at 2.
7. Dr. MacGinnitie’s Supplemental Report
Dr. MacGinnitie criticized Dr. Akbari’s BLAST search and opined the “degree of sequence
similarity between HPV L1 proteins and [MBP] [] identified by Dr. Akbari is not notable.”
Resp’t’s Ex. F at 2. Dr. MacGinnitie pointed out that Dr. Akbari did not provide the details of the
searches he conducted or the official results. Without that information, he undertook a BLAST
search himself using HPV11 and HPV18 L1 proteins versus human MBP. Id. “Initially, [he] got
no matches, but when [he] loosened the stringency of the search (using the Expect Value discussed
below) it returned a single match for each search with the one for HPV 11 shown here.” Id.
15
Id. Dr. MacGinnitie explained the Expect Value, “which evaluates how unlikely a particular match
is – in other words, how probable or improbable it is that such a match could have occurred by
chance.” Id. at 3. “The built in ‘cutoff’ is an expect value less than or equal to 0.05 and using this
cutoff [Dr. MacGinnitie] got zero matches.” Id. “Only when [he] increased the cutoff to 10
(meaning 10 such matches between [two] sequences would be expected by chance) did [he] obtain
a match.” Id. Despite Dr. MacGinnitie finding this homology, he opined “[s]equence similarity
alone is not enough to demonstrate molecular mimicry as a trigger of disease.” Id. at 4. The
Institute of Medicine (“IOM”)28 discussed this and wrote that “[m]any such homologies exist, and
the vast majority of these are not associated with biologically relevant autoimmune phenomenon
or actual human disease.” Id. (quoting Resp’t’s Ex. F, Tab 6 at 10). Kanduc et al.29 stated that if
sequence homology was enough to induce molecular mimicry, then “viral infections should be a
practically infinite source or autoimmunity diseases since this study demonstrates that viral 5-mer
matches are disseminated throughout practically all the human proteome and each viral match is
repeated almost more than 10 times.” Resp’t’s Ex. F, Tab 3 at 11. Dr. MacGinnitie summarized,
“Dr. Akbari has not identified significant homology between the HPV L1 protein in Gardasil and
human MBP nor is a simple sequence homology enough to trigger autoimmunity.” Resp’t’s Ex. F
at 6.
Dr. MacGinnitie added that “gangliosides and proteins are distinct classes of molecules so
there is no reason to think that T-cells that recognize MBP would also recognize gangliosides.”
Resp’t’s Ex. F at 6 (citing Resp’t’s Ex. F, Tab 14).30 Dr. MacGinnitie then cited Ziganshin et al.31
for the proposition that autoantibodies against MBP are not present in patients with GBS and
criticized Dr. Akbari’s interpretation of Cornblath et al. for saying otherwise. Id. at 7 (citing
Resp’t’s Ex. F, Tab 17; Pet’r’s Ex. 74). “Thus, even if Dr. Akbari were correct that HPV
vaccination could trigger production of an autoimmune response to MBP, and [Dr. MacGinnitite]
do[es] not agree with this assertion, it would not explain development of GBS.” Id. Dr.
MacGinnitie noted “that antibodies against MBP are typically associated with multiple sclerosis,
a demyelinating disorder of the central, not peripheral nervous system.” Id. Dr. MacGinnitie
reiterated that Petitioner “had positive testing for [two] gangliosides, GM1 and GD1a with the
28
Inst. of Med., Adverse Effects of Vaccines: Evidence Causality (Kathleen Stratton et al. eds., 2012).
29
Darja Kanduc et al., Massive Peptide Sharing Between Viral and Human Proteomes, 29 PEPTIDES 1755
(2008).
30
Jon D. Laman et al., Guillain-Barré Syndrome: Expanding the Concept of Molecular Mimicry, 43
TRENDS IMMUNOLOGY 296 (2022).
31
Rustam H. Ziganshin et al., The Pathogenesis of the Demyelinating Form of Guillain-Barre Syndrome
(GBS): Proteo-Peptidomic and Immunological Profiling of Physiological Fluids, 15 MOLECULAR &
CELLULAR PROTEOMICS 2366 (2016).
16
latter being associated with GBS.” Id. at 8 (citing Pet’r’s Ex. 3 at 155–56). “Thus, development of
these anti-ganglioside antibodies provides a clear immunologic explanation for development of
diseases, with no need to invoke autoimmunity against proteins such as MBP.” Id.
8. Dr. Brier’s Supplemental Report
Dr. Brier submitted a supplemental report criticizing Dr. Jeret’s opinions and addressing
“how one weighs evidence in the setting of imperfect data.” Resp’t’s Ex. E at 1. He compared
different types of literature filed including large epidemiologic studies and case reports. Id. at 1–
4. He also further discussed diagnostic criteria, although he agreed GBS is the correct diagnosis.
Id. at 4–6. His opinion remained that “there is insufficient evidence to infer that HPV vaccination
causes GBS.” Id. at 6.
IV. Applicable Legal Standards
A. Burden of Proof
The Vaccine Act was established to compensate vaccine-related injuries and deaths. §
10(a). “Congress designed the Vaccine Program to supplement the state law civil tort system as a
simple, fair and expeditious means for compensating vaccine-related injured persons. The
Program was established to award ‘vaccine-injured persons quickly, easily, and with certainty and
generosity.’” Rooks v. Sec’y of Health & Hum. Servs., 35 Fed. Cl. 1, 7 (1996) (quoting H.R. Rep.
No. 908 at 3, reprinted in 1986 U.S.C.C.A.N. at 6287, 6344).
Petitioner’s burden of proof is by a preponderance of the evidence. § 13(a)(1). The
preponderance standard requires a petitioner to demonstrate that it is more likely than not that the
vaccine at issue caused the injury. Moberly v. Sec’y of Health & Hum. Servs., 592 F.3d 1315,
1322 n.2 (Fed. Cir. 2010). Proof of medical certainty is not required. Bunting v. Sec’y of Health
& Hum. Servs., 931 F.2d 867, 873 (Fed. Cir. 1991).
B. Causation
To receive compensation through the Program, Petitioner must prove either (1) that he
suffered a “Table Injury”—i.e., an injury listed on the Vaccine Injury Table—corresponding to a
vaccine that he received, or (2) that he suffered an injury that was actually caused by a vaccination.
See §§ 11(c)(1), 13(a)(1)(A); Capizzano, 440 F.3d at 1319–20. Here, Petitioner does not assert a
Table claim; therefore, Petitioner must prove a vaccine he received caused his injury. To do so,
Petitioner must establish, by preponderant evidence: “(1) a medical theory causally connecting the
vaccination and the injury; (2) a logical sequence of cause and effect showing that the vaccination
was the reason for the injury; and (3) a showing of a proximate temporal relationship between
vaccination and injury.” Althen, 418 F.3d at 1278.
A petitioner must offer a scientific or medical theory that answers in the affirmative the
question: “can the vaccine[] at issue cause the type of injury alleged?” See Pafford v. Sec’y of
Health & Hum. Servs., No. 01-0165V, 2004 WL 1717359, at *4 (Fed. Cl. Spec. Mstr. July 16,
2004), mot. for rev. denied, 64 Fed. Cl. 19 (2005), aff’d, 451 F.3d 1352 (Fed. Cir. 2006). To satisfy
this prong, a petitioner’s theory must be based on a “sound and reliable medical or scientific
17
explanation.” Knudsen v. Sec’y of Health & Hum. Servs., 35 F.3d 543, 548 (Fed. Cir. 1994). Such
a theory must only be “legally probable, not medically or scientifically certain.” Id. at 548–49. A
petitioner is not required to identify “specific biological mechanisms” to establish causation, nor
are they required to present “epidemiologic studies, rechallenge[] the presence of pathological
markers or genetic disposition, or general acceptance in the scientific or medical communities.”
Capizzano, 440 F.3d at 1325 (quoting Althen, 418 F.3d at 1280). Scientific and “objective
confirmation” of the medical theory with additional medical documentation is unnecessary. Althen,
418 F.3d at 1278–81; see also Moberly, 592 F.3d at 1322. Petitioner need not make a specific type
of evidentiary showing, i.e., “epidemiologic studies, rechallenge, the presence of pathological
markers or genetic predisposition, or general acceptance in the scientific or medical communities
to establish a logical sequence of cause and effect.” Capizzano, 440 F.3d at 1325. However,
Petitioner cannot establish entitlement to compensation based solely on his assertions; rather, a
vaccine claim must be supported either by medical records or by the opinion of a medical doctor.
§ 13(a)(1). Furthermore, as the Federal Circuit has made clear, “simply identifying a ‘plausible’
theory of causation is insufficient for a petitioner to meet her burden of proof.” LaLonde v. Sec’y
of Health & Hum. Servs., 746 F.3d 1334, 1339 (Fed. Cir. 2014) (citing Moberly, 592 F.3d at 1322).
Testimony that merely expresses the possibility—not the probability—is insufficient, by itself, to
substantiate a claim that such an injury occurred. See Waterman v. Sec’y of Health & Hum. Servs.,
123 Fed. Cl. 564, 573–74 (2015) (denying Petitioner’s motion for review and noting that a possible
causal link was not sufficient to meet the preponderance standard). While certainty is by no means
required, a possible mechanism does not rise to the level of preponderance. Moberly, 592 F.3d at
1322; see also de Bazan v. Sec’y of Health & Hum. Servs., 539 F.3d 1347, 1351 (Fed. Cir. 2008).
Rather, “[a] petitioner must provide a reputable medical or scientific explanation that pertains
specifically to the petitioner’s case.” Moberly, 592 F.3d at 1322.
Next, a petitioner must prove that the vaccine actually did cause the alleged injury in a
particular case. See Pafford, 2004 WL 1717359, at *4; Althen, 418 F.3d at 1279. A petitioner does
not meet this obligation by showing only a temporal association between the vaccination and the
injury; instead, the petitioner “must explain how and why the injury occurred.” Pafford, 2004 WL
1717359, at *4 (emphasis in original). In particular, Petitioner must prove that the vaccine was
“not only [the] but-for cause of the injury but also a substantial factor in bringing about the injury.”
Moberly, 592 F.3d at 1321 (quoting Shyface v. Sec’y of Health & Hum. Servs., 165 F.3d 1344,
1352–53 (Fed. Cir. 1999)); see also Pafford v. Sec’y of Health & Hum. Servs., 451 F.3d 1352,
1355 (Fed. Cir. 2006). The received vaccine, however, need not be the predominant cause of the
injury. Shyface, 165 F.3d at 1351. The special master in Pafford noted petitioners “must prove []
both that her vaccinations were a substantial factor in causing the illness . . . and that the harm
would not have occurred in the absence of the vaccination.” 2004 WL 1717359, at *4 (citing
Shyface, 165 F.3d at 1352). A reputable medical or scientific explanation must support this logical
sequence of cause and effect. Hodges v. Sec’y of Health & Hum. Servs., 9 F.3d 958, 961 (Fed Cir.
1993) (citation omitted).
Lastly, a petitioner must show that the timing of the injury fits with the causal theory. See
Althen, 418 F.3d at 1278. For example, if a petitioner’s theory involves a process that takes several
days to develop after vaccination, an injury that occurred within a day of vaccination would not be
temporally consistent with that theory. Conversely, if the theory is one that anticipates a rapid
development of a reaction post-vaccination, the development of the alleged injury weeks or months
18
post-vaccination would not be consistent with that theory. See de Bazan, 539 F.3d at 1352.
Causation-in-fact cannot be inferred from temporal proximity alone. See Grant v. Sec’y of Health
& Hum. Servs., 956 F.2d 1144, 1148 (Fed. Cir. 1992); Thibaudeau v. Sec’y of Health & Hum.
Servs., 24 Cl. Ct. 400, 403–04 (1991); see also Hasler v. United States, 718 F.2d 202, 205 (6th
Cir. 1983) (“[w]ithout more, [a] proximate temporal relationship will not support a finding of
causation”).
In determining whether Petitioner is entitled to compensation, the special master shall
consider all materials in the record, including “any . . . conclusion, [or] medical judgment . . .
which is contained in the record regarding . . . causation.” § 13(b)(1)(A). The undersigned must
weigh the submitted evidence and the testimony of the parties’ proffered experts and rule in
Petitioner’s favor when the evidence weighs in her favor. See Moberly, 592 F.3d at 1325–26
(“Finders of fact are entitled—indeed, expected—to make determinations as to the reliability of
the evidence presented to them and, if appropriate, as to the credibility of the persons presenting
that evidence.”); Althen, 418 F.3d at 1280 (noting that “close calls” are resolved in Petitioner’s
favor). A petitioner who satisfies her burden is entitled to compensation unless Respondent can
prove, by a preponderance of the evidence, that the vaccinee’s injury is “due to factors unrelated
to the administration of the vaccine.” § 13(a)(1)(B). However, if a petitioner fails to establish a
prima facie case, the burden does not shift. Bradley v. Sec’y of Health & Hum. Servs., 991 F.2d
1570, 1575 (Fed. Cir. 1993).
IV. Discussion
A. Althen Prong One
Dr. Akbari opined that “molecular mimicry and induction of inflammasome are credible
medical theor[ies] causally linking the HPV vaccination to injuries that [Petitioner] experienced.”
Pet’r’s Ex. 70 at 16. Dr. Jeret opined “molecular mimicry is the basis for GBS after HPV vaccine.”
Pet’r’s Ex. 12 at 8. I find Petitioner failed to provide preponderant evidence of a sound and reliable
medical theory explaining how the HPV vaccine can cause GBS.
I note at the outset that Dr. Akbari referred to the Tdap vaccine throughout his first report.
See, e.g., Pet’r’s Ex. 28 at 5 (“My research into your particular question concluded that the theory
of molecular mimicry supports that Tdap vaccination can plausibly cause an adverse immune cross
reaction and result in the onset of GBS.”), 16 (“A second criterion for implicating molecular
mimicry. . . is to demonstrate the plausibility of cross-reactivity by autoreactive T-cells or
autoantibodies with a microbial antigen, or in this case to a component of the Tdap vaccine.”). Dr.
Akbari never compared the Tdap vaccine to the HPV vaccine or explained how evidence relevant
to one is applicable to the other. It appears these references may have been copied from another
expert report in a different case. See also Pet’r’s Ex. 70 at 13 (referencing conditions (pericarditis
and rheumatoid arthritis) and doctors (Dr. LaRue and Dr. Bates) not involved in this case). I will
not address his opinions on other vaccines or other conditions to the extent he did not compare
them to the vaccine and injury at issue in this case. An expert may “extrapolate from existing data”
where the reasons for extrapolation are transparent and persuasive. K.O. v. Sec’y of Health & Hum.
Servs., No. 13-472V, 2016 WL 7634491 (Fed. Cl. July 7, 2016) (quoting Snyder v. Sec’y of Health
& Hum. Servs., 88 Fed. Cl. 706, 743 (2009)).
19
Overall, I find Dr. Akbari’s opinions as to Althen prong one are underdeveloped and
conclusory in nature. When evaluating whether petitioners have carried their burden of proof,
special masters consistently reject “conclusory expert statements that are not themselves backed
up with reliable scientific support.” Kreizenbeck v. Sec’y of Health & Hum. Servs., No. 08-209V,
2018 WL 3679843, at *31 (Fed. Cl. Spec. Mstr. June 22, 2018), mot. for rev. denied, decision
aff’d, 141 Fed. Cl. 138, aff’d, 945 F.3d 1362 (Fed. Cir. 2020). I will not rely on “opinion evidence
that is connected to existing data only by the ipse dixit of the expert.” Prokopeas v. Sec’y of Health
& Hum. Servs., No. 04-1717V, 2019 WL 2509626, at *19 (Fed. Cl. Spec. Mstr. May 24, 2019)
(quoting Moberly, 592 F.3d at 1315). Instead, special masters are expected to carefully scrutinize
the reliability of each expert report submitted. See id.
Dr. Akbari’s proposed theory was confusing as he focused on molecular mimicry but
inexplicably injected inflammasome and T-cell dysfunction into his arguments. He did not provide
needed context for a relationship between either of these concepts and his main theory; nor did he
propose alternative theories (with evidentiary support) that center on either. See e.g., Pet’r’s Ex.
70 at 9 (Dr. Akbari writing that “inflammasome and IL-1 are capable of suppressing the Treg
function tremendously,” but that “[i]f you add IL-1 to Tregs, the cells are not able to exert their
suppressive effect,” yet “the induction of inflammasome by HPV vaccine is capable of suppressing
Tregs and increas[ing] the chance of induction of demyelinating disease”). These vague,
conclusory, and contradictory statements muddle any persuasive argument for a biological
mechanism. Moreover, while Respondent discussed Dr. Akbari’s other potential theories in his
responsive brief, Petitioner chose not to rebut any of those criticisms in his reply brief and
maintained his focus on the molecular mimicry theory. I find any other alternative theories raised
by Dr. Akbari lack the detail sufficient to determine reliability or reasonableness based on a
preponderant standard. Accordingly, I too will focus my analysis on molecular mimicry.
Dr. Akbari conducted a BLAST search to attempt to show homology between components
of the HPV vaccine and MBP as the human antibody target for GBS. Dr. Akbari asserted he found
five amino acids featuring three consecutive matches at critical binding points and opined that such
homology is adequate to trigger molecular mimicry. Additionally, he opined there were three
amino acids whose similarity is “tolerated.” Pet’r’s Ex. 70 at 2. Dr. MacGinnitie disputed the
relevancy of any association between MBP and GBS and opined that gangliosides, which are
associated with GBS, should have been applied instead.32 Nonetheless, even if MBP was relevant
to GBS, Dr. MacGinnitie opined the HPV vaccine would not likely induce GBS. First, Dr. Akbari
did not file his search parameters, and Dr. MacGinnitie was unable to replicate Dr. Akbari’s alleged
homology results. Second, even if he could, Dr. MacGinnitie believed the linear peptide
homologies of four (HPV 11) and five (HPV 18) were insignificant.
Kanduc et al. and the IOM state that homology alone is not enough to induce molecular
mimicry and subsequently, autoimmune diseases. However, we do not reach the issue of homology
here as Petitioner applied his molecular mimicry theory to MBP, and Petitioner has not proved by
preponderant evidence that MBP is the target antigen in GBS.
32
The significance of gangliosides in this case is discussed more below in Althen Prong two.
20
Cornblath et al. did not support the finding that MBP plays a pivotal role in the
development of GBS; in fact, it did not study the presence of MBP antibodies in GBS. Rather, it
studied the presence of MBP itself (the protein, not the antibodies) in the CSF of patients with
GBS and concluded that “MBP-like material is present in the CSF of most patients with
longstanding demyelinating polyradiculoneuropathies and probably reflects detection of
peripheral nervous system P1 protein.” Pet’r’s Ex. 74 at 1. Like here, Cornblath et al. has been
used to support this assertion previously in the Program and was likewise found to be inapplicable
to vaccine-caused GBS. See Blackburn v. Sec’y of Health & Hum. Servs., 2015 WL 425935 (Fed.
Cl. Spec. Mstr. 2015) (Dr. Steinman implicated an immune attack on MBP to show how the HPV
vaccine caused GBS/CIDP. Dr. Steinman conceded that Cornblath et al. did not support the
proposition that MBP is the target antigen in GBS and the Court ultimately rejected Dr. Steinman’s
theory, dismissing the case.). Ziganshin et al. tested serum from GBS patients and controls for
MBP antibodies and found no “statistically significant difference.” Resp’t’s Ex. F, Tab 17 at 7.
They did however find that gangliosides GM1 and GD1a were targets in the AMAN variant of
GBS. Petitioner did not respond to Dr. MacGinnitie’s opposition to Dr. Akbari’s theory on this
point or apply his theory to these gangliosides. Thus, the target antigen of GBS is not established
here and Dr. Akbari’s conflicting opinions, on this point and others, are not as persuasive without
further explanation or supporting authority.33
Dr. Jeret also proposed molecular mimicry but only discussed it generally and did not
provide context for its application to GBS caused by the HPV vaccine. He asserted that the
mechanism that leads to GBS following the flu vaccine can be applied to HPV vaccination without
further explanation. To the extent that molecular mimicry is offered as a theory, it must be
supported by a sound and reliable medical or scientific explanation.” Knudsen, 35 F.3d at 548.
There must also be some degree of selectivity. See W.C. v. Sec’y of Health & Hum. Servs., 704
F.3d 1352, 1360 (2013) (finding that a petitioner cannot prevail by simply invoking a biological
term, or by showing that the mechanism is a valid theory to explain how other triggers may have
induced other diseases and determining that a petitioner must produce additional evidence that the
mechanism can cause that vaccine to cause a specific disease); Caves v. Sec’y of Health & Hum.
Servs., 100 Fed. Cl. 119, 135 (2011), aff’d, 463 F. App’x. 932 (2012); McKown v. Sec’y of Health
& Hum. Servs., No. 15-1451, 2019 WL 4072113, at *50 (Fed. Cl. Spec. Mstr. July 15, 2019).
Petitioner does not have to provide a specific mechanism, but it must be detailed enough to apply
to the administered vaccine and alleged injury in this case. Otherwise, any vaccination, by nature
of its purpose to illicit an immune response, could be asserted as the cause of any autoimmune
disease that later developed in an individual, and Althen prong one “would be rendered
meaningless.” See Caves, 100 Fed. Cl. at 135; see also McKown, 2019 WL 4072113, at *50
(“[M]erely chanting the words ‘molecular mimicry’ in a Vaccine Act case does not render a
causation theory scientifically reliable, absent additional evidence specifically tying the
mechanism to the injury and/or the vaccine in question.”).
Several studies were cited regarding an association, or lack thereof, between the HPV
vaccine and GBS. For example, Souayah et al. used data from VAERS to conclude there was an
increased risk of GBS after vaccination when they identified 69 cases of GBS within six weeks of
HPV vaccination. Miranda et al. found an increased risk of GBS after HPV vaccination. And while
33
Because Petitioner has not provided preponderant evidence of the target antigen here, we do not reach
the issue of sequence homology and whether it is sufficient.
21
Boender et al. (cited by both parties) found “a signal of increased risk of GBS after HPV
vaccination,” they concluded that the “absolute and relative risk of GBS after HPV vaccination is
very low and lacks statistical significance.” Pet’r’s Ex. 84 at 1. While epidemiologic studies are
not required to be successful, when the petitioner files epidemiologic studies himself concluding
there is no association between the subject vaccine and injury, that evidence is evaluated along
with all other evidence that is submitted in favor of or against Petitioner’s arguments.
After consideration of the evidence, I find that Petitioner has not presented preponderant
evidence of a sound and reliable medical theory to explain how the HPV vaccine can cause GBS.
Therefore, Petitioner does not meet his burden pursuant to Althen prong one.
B. Althen Prong Two
Both parties agreed the diagnosis is GBS. But a successful argument pursuant to Althen
prong two is heavily dependent on a reliable causation theory. Petitioner’s inability to meet his
burden demonstrating how the HPV vaccine can cause GBS effectively precludes him from being
able to show that his symptoms were actually caused by the vaccine according to said theory.
Moreover, neither Dr. Akbari nor Dr. Jeret analyzed Petitioner’s clinical presentation in the context
of their theory. This alone hinders any meaningful discussion on prong two.
Petitioner tested positive for the GM1 and GD1a ganglioside antibodies when he was
diagnosed with GBS. Petitioner’s treating physicians explained these were associated with his
type of GBS, the AMAN variant. See, e.g., Pet’r’s Ex. 3 at 155 (test results), 51 (Dr. Talmasov
noting an association between GM1/GD1a and GBS); Pet’r’s Ex. 4 at 4 (Dr. Zakin noting
Petitioner’s elevated GM1 and GD1A in association with his GBS), 189, 245, 305, 349, 386 (Dr.
Zakin consistently stating Petitioner had a motor variant of GBS associated with a positive GM1
antibody). Dr. MacGinnitie also opined that studies show that GM1 and GD1a antibodies are
associated with AMAN; “[t]hus, development of these anti-ganglioside antibodies provides a clear
immunologic explanation for development of diseases, with no need to invoke autoimmunity
against proteins such as MBP.” Resp’t’s Ex. F at 8. Neither Dr. Akbari nor Dr. Jeret addressed
this.
While Petitioner’s neurologist Dr. Zakin noted Petitioner’s GBS was “in the setting of
recent HPV vaccination,” she did not opine as to how the two were causally connected, if at all.
Pet’r’s Ex. 4 at 1.
In considering the reliability of a petitioner’s evidence of a prima facie case, the special
master may consider alternative causes for a petitioner’s condition that are reasonably raised in the
record, even if the respondent does not pursue a formal alternative cause argument. Doe v. Sec’y
of Health & Hum. Servs., 601 F.3d 1349, 1358 (Fed. Cir. 2010). Thus, in weighing a petitioner’s
case-in-chief, a special master may consider evidence that the petitioner’s alleged injury could
have been caused by alternative causes. Id.
During Petitioner’s hospitalization, it was noted that Petitioner had an HPV vaccine and a
cold34 prior to the onset of symptoms. Dr. Jeret opined that Petitioner’s “preceding URI—whose
34
Although one of the doctors noted there was no preceding illness. Pet’r’s Ex. 3 at 77–78.
22
timing is not specified, whose associated symptoms are not specified, and which is never
diagnosed as influenza or considered by any of the practitioners to have been significant—did not
play a role in his subsequent development of GBS.” Pet’r’s Ex. 12 at 9. Dr. MacGinnitie opined it
was “certainly possible” that Petitioner’s URI was influenza and “was the trigger of his GBS, given
that influenza, unlike HPV is a known trigger of GBS.” Resp’t’s Ex. A at 14. This is not
preponderant evidence of actual causation for either the alleged cold or the HPV vaccine in
Petitioner’s case.
As indicated above, Petitioner did not apply molecular mimicry, or any theory, in the
context of gangliosides, particularly those involved in GBS. For these reasons, I find Petitioner
has failed to provide preponderant evidence of a logical sequence of cause and effect between his
HPV vaccination and his GBS.
C. Althen Prong Three
Petitioner asserted that the onset of his GBS was 10–11 days after vaccination. Dr. Akbari
proposed a mechanism of prime and recall response to explain how 10 days is an appropriate
temporal association, between Petitioner’s HPV vaccination and the onset of his symptoms,
consistent with causation. See Pet’r’s Ex. 28 at 22; Pet’r’s Ex. 70 at 11–12, 16. He wrote that “if
the same stimuli [that are produced in the first dose a vaccine] such as the second dose of vaccine
are given a few weeks to a few months after the initial dose, the memory cells begin to replicate
and produce cytokines in a significantly short period of time.” Pet’r’s Ex. 28 at 22. Dr. Akbari
pointed out the significance of this since Petitioner “did not experience any adverse effects after
his first dose but developed GBS 11 days after the second dose.” Pet’r’s Ex. 70 at 12. Thus,
according to Dr. Akbari, “the timing between receipt of the second vaccine and development of
demyelinating disease . . . is an appropriate timeframe for the immune-mediated mechanism of
causing neuropathy.” Pet’r’s Ex. 28 at 22. Dr. Jeret opined “GBS beginning 3–42 days after the
vaccine would be consistent with a causal relationship based on molecular mimicry” and that
Petitioner’s GBS began 10 days after vaccination. Pet’r’s Ex. 12 at 11.
Respondent “does not contest that [P]etitioner’s GBS began within a timeframe that is
reasonable to infer causation.” Resp’t’s Response at 29. Based on the medical literature filed, this
would be a medically acceptable timeframe. However, and as discussed above, since Petitioner
has not provided preponderant evidence that the HPV vaccine can cause GBS, Petitioner ultimately
fails to show preponderant evidence that his vaccine caused his condition.
V. Conclusion
After a careful review of the record, Petitioner has failed to provide preponderant evidence
that his January 14, 2020 HPV vaccine caused his GBS. Accordingly, Petitioner’s claim is
DENIED. Absent a timely motion for review, the Clerk is directed to enter judgment dismissing
this case for insufficient proof in accordance with Vaccine Rule 11(a). 35
35
Pursuant to Vaccine Rule 11(a), entry of judgment is expedited by the parties’ joint filing of a notice
renouncing the right to seek review.
23
IT IS SO ORDERED.
s/Herbrina D. S Young
Herbrina D. S. Young
Special Master
24