Evidence dossier · candidate cand-shingles-herpes-zoster · VICP program · · DRAFT — not a determination
This is a draft research-tracking dossier, not a determination that Shingles (zoster) vaccine causes Herpes zoster, and not an incidence or legal finding. All evidence is flagged needs_human_review and must be reviewed before any page is published or cited. Every value is grounded in retrieved citations (PMID + retrieval date); unsourced items read "no evidence found / not assessable". Symmetric search: every supporting query has a mirror/null query, and zeros are shown (negative dossiers report the absence of signal).
Claim matrix (C1–C6, computed)
Claim
Label
Status
Missing nodes
C1
Coherent clinical object exists
supported
C2
Consistent temporal window
supported
C3
Epidemiologic excess risk
contested
C4
Consistency / replication
contested
C5
Specificity (product / dose)
contested
C6
Biological mechanism
contested
Two evidentiary bars apply to the epi nodes/claims (C3, C4): · VICP — preponderance of the evidence. · CICP (off-Table) — compelling, reliable, valid medical and scientific evidence (higher bar).
Bradford Hill assessment (computed)
Each viewpoint is derived from the node statuses below (see the framework crosswalk in compensation-tables-schema.md §8). Hill's viewpoints are aids to judgement, not a scoring checklist that proves causation; temporality is the only strictly necessary criterion.
Viewpoint
What it asks
Status (from evidence)
Temporality(necessary)
cause precedes effect in a plausible window (necessary)
NASEM (formerly IOM), "Adverse Effects of Vaccines: Evidence and Causality" (2011, updated 2024). Independent grading of epidemiologic and mechanistic evidence, synthesized into one of four causal-conclusion categories. This is a computed approximation of that framework, not a NASEM determination. See compensation-tables-schema.md §8bis.
Case-definition standard: no established case definition (needs_human_review — not in spec §1's named-standard list) — governs the case-certainty scale on A1/A2/A6/A8 below. See compensation-tables-schema.md §8ter.
Evidence matrix (68 nodes by workstream)
68 of 68 nodes evaluated · 136 PubMed queries logged (supporting + mirror, incl. zeros). Statuses are computed from retrieved citations; not hand-set.
Definition & attribution 24/24 evaluated
A1 · Case reportssupports
Measure: New definite object in risk window T Comparator: Pre-vaccination baseline Hit rule: Definite object present, onset in window, competing causes considered
Finding: PMID 37220294 reports a case of herpes zoster triggered by Shingrix (recombinant zoster vaccine) in an immunocompetent patient; PMID 39296531 reports herpes zoster ophthalmicus following recombinant zoster vaccine in a 59-year-old man. Both cases describe new definite herpes zoster in the risk window after shingles vaccination, with competing causes considered.
Case-certainty distribution (no established case definition): 1 Definite, 3 Probable, 4 Possible/unclassifiable. Transparency layer — does not change this node's status or feed C1–C6.
supporting: Shingles (zoster) vaccine Herpes zoster case report OR case series Case reports pubmed · 66453 hits · run 2026-09-09
mirror: Shingles (zoster) vaccine Herpes zoster alternative diagnosis OR not vaccine-related pubmed · 4069 hits · run 2026-09-09
22 retrieved record(s)
supports_node 36650730 · The American journal of case reports (2023) — Herpes Zoster Following COVID-19 Vaccine Booster.
supports_node 28944968 · Pediatric dermatology (2017) — Pediatric vaccine-strain herpes zoster: a case series.
supports_node 39296531 · IDCases (2024) — Herpes zoster ophthalmicus following recombinant zoster vaccine: A case report and brief literature review.
supports_node 42438029 · Internal medicine (Tokyo, Japan) (2026) — Disseminated Varicella-Zoster Virus Infection Following a Live Attenuated Varicella Vaccine (Oka Strain) in a Patient with Rheumatoid Arthritis: A Case Report.
supports_node 37220294 · Dermatology online journal (2023) — A rare case of herpes zoster triggered by a non-live varicella vaccine.
ambiguous 39223824 · Acta dermatovenerologica Alpina, Pannoni (2024) — Acute psoriasis exacerbation by recombinant zoster vaccine: a case report.
supports_node 34428545 · International journal of infectious dise (2021) — Herpes zoster after COVID vaccination.
supports_node 34222134 · Clinical and experimental vaccine resear (2021) — A rare case of shingles after COVID-19 vaccine: is it a possible adverse effect?
A2 · Series with objective confirmationno_data
Measure: Definite object plus objective test Comparator: Reference range / diagnostic criteria Hit rule: Objective confirmation in >=1 case per the working definition
Finding: No retrieved evidence describes objective confirmation of Herpes zoster following Shingles (zoster) vaccine; all retrieved papers concern COVID-19, varicella vaccine, or unrelated vaccines.
Case-certainty distribution (no established case definition): 2 Definite, 2 Probable. Transparency layer — does not change this node's status or feed C1–C6.
Cited: (none)
supporting: Shingles (zoster) vaccine Herpes zoster case report OR case series Series with objective confirmation pubmed · 5926 hits · run 2026-09-09
mirror: Shingles (zoster) vaccine Herpes zoster alternative diagnosis OR not vaccine-related pubmed · 4069 hits · run 2026-09-09
17 retrieved record(s)
supports_node 36650730 · The American journal of case reports (2023) — Herpes Zoster Following COVID-19 Vaccine Booster.
supports_node 28944968 · Pediatric dermatology (2017) — Pediatric vaccine-strain herpes zoster: a case series.
supports_node 42438029 · Internal medicine (Tokyo, Japan) (2026) — Disseminated Varicella-Zoster Virus Infection Following a Live Attenuated Varicella Vaccine (Oka Strain) in a Patient with Rheumatoid Arthritis: A Case Report.
ambiguous 34428545 · International journal of infectious dise (2021) — Herpes zoster after COVID vaccination.
supports_node 34222134 · Clinical and experimental vaccine resear (2021) — A rare case of shingles after COVID-19 vaccine: is it a possible adverse effect?
ambiguous 33647971 · QJM : monthly journal of the Association (2021) — COVID-19 vaccine-related myositis.
does_not_resolve 37775180 · Clinical medicine (London, England) (2023) — SARS-CoV-2 vaccines and myocarditis.
A3 · Onset histogramno_data
Measure: Distribution of onset times after dose Comparator: Pre-specified risk window Hit rule: Onset clusters inside the pre-specified window (not uniform/flat)
Finding: The retrieved evidence consists entirely of case reports and case series describing herpes zoster (HZ) following COVID-19 vaccines (PMIDs 36650730, 34428545, 34222134, 34397201) and HZ following the recombinant zoster vaccine (RZV) itself (PMIDs 39296531, 37220294, 35431886), but none of these reports provide a systematic onset histogram or statistical clustering of onset times within a pre-specified risk window that would count as a 'hit' under the node's rule.
Cited: (none)
supporting: Shingles (zoster) vaccine Herpes zoster case report OR case series Onset histogram pubmed · 285 hits · run 2026-09-09
mirror: Shingles (zoster) vaccine Herpes zoster alternative diagnosis OR not vaccine-related pubmed · 4069 hits · run 2026-09-09
23 retrieved record(s)
ambiguous 36650730 · The American journal of case reports (2023) — Herpes Zoster Following COVID-19 Vaccine Booster.
supports_node 28944968 · Pediatric dermatology (2017) — Pediatric vaccine-strain herpes zoster: a case series.
supports_node 42438029 · Internal medicine (Tokyo, Japan) (2026) — Disseminated Varicella-Zoster Virus Infection Following a Live Attenuated Varicella Vaccine (Oka Strain) in a Patient with Rheumatoid Arthritis: A Case Report.
supports_node 34428545 · International journal of infectious dise (2021) — Herpes zoster after COVID vaccination.
supports_node 34222134 · Clinical and experimental vaccine resear (2021) — A rare case of shingles after COVID-19 vaccine: is it a possible adverse effect?
supports_node 39296531 · IDCases (2024) — Herpes zoster ophthalmicus following recombinant zoster vaccine: A case report and brief literature review.
ambiguous 25962929 · The Journal of pediatrics (2015) — Vaccine-Associated Herpes Zoster.
supports_node 34397201 · Journal of drugs in dermatology : JDD (2021) — Herpes Zoster Following COVID-19 Vaccination.
A4 · Temporal plausibilityno_data
Measure: Onset latency vs object pathophysiology Comparator: Object's known natural latency Hit rule: Onset latency consistent with the object's pathophysiology
Finding: The retrieved evidence includes a case report of herpes zoster following recombinant zoster vaccine (RZV) administration, with onset latency reported but not systematically compared to the expected pathophysiology of vaccine-strain reactivation; the evidence is limited to a single case report.
supporting: Shingles (zoster) vaccine Herpes zoster case report OR case series Temporal plausibility pubmed · 314 hits · run 2026-09-09
mirror: Shingles (zoster) vaccine Herpes zoster alternative diagnosis OR not vaccine-related pubmed · 4069 hits · run 2026-09-09
22 retrieved record(s)
ambiguous 36650730 · The American journal of case reports (2023) — Herpes Zoster Following COVID-19 Vaccine Booster.
supports_node 28944968 · Pediatric dermatology (2017) — Pediatric vaccine-strain herpes zoster: a case series.
ambiguous 34428545 · International journal of infectious dise (2021) — Herpes zoster after COVID vaccination.
ambiguous 34222134 · Clinical and experimental vaccine resear (2021) — A rare case of shingles after COVID-19 vaccine: is it a possible adverse effect?
supports_node 39296531 · IDCases (2024) — Herpes zoster ophthalmicus following recombinant zoster vaccine: A case report and brief literature review.
ambiguous 25962929 · The Journal of pediatrics (2015) — Vaccine-Associated Herpes Zoster.
supports_node 34397201 · Journal of drugs in dermatology : JDD (2021) — Herpes Zoster Following COVID-19 Vaccination.
does_not_resolve 36752132 · Revista espanola de quimioterapia : publ (2023) — Status of Herpes Zoster and Herpes Zoster Vaccines in 2023: A position paper.
A5 · Onset-interval documentationno_data
Measure: Onset interval documented in source Comparator: Dose date Hit rule: Onset interval is recorded (not imputed) in a primary source
Finding: No retrieved evidence specifically documents that the onset interval of Herpes zoster attributed to Shingles (zoster) vaccine is recorded in a primary source; all reports mention onset but do not confirm that the interval was recorded (not imputed) per the node definition.
Cited: (none)
supporting: Shingles (zoster) vaccine Herpes zoster case report OR case series Onset-interval documentation pubmed · 283 hits · run 2026-09-09
mirror: Shingles (zoster) vaccine Herpes zoster alternative diagnosis OR not vaccine-related pubmed · 4069 hits · run 2026-09-09
23 retrieved record(s)
supports_node 36650730 · The American journal of case reports (2023) — Herpes Zoster Following COVID-19 Vaccine Booster.
supports_node 28944968 · Pediatric dermatology (2017) — Pediatric vaccine-strain herpes zoster: a case series.
supports_node 42438029 · Internal medicine (Tokyo, Japan) (2026) — Disseminated Varicella-Zoster Virus Infection Following a Live Attenuated Varicella Vaccine (Oka Strain) in a Patient with Rheumatoid Arthritis: A Case Report.
supports_node 34428545 · International journal of infectious dise (2021) — Herpes zoster after COVID vaccination.
ambiguous 34222134 · Clinical and experimental vaccine resear (2021) — A rare case of shingles after COVID-19 vaccine: is it a possible adverse effect?
ambiguous 25962929 · The Journal of pediatrics (2015) — Vaccine-Associated Herpes Zoster.
supports_node 39296531 · IDCases (2024) — Herpes zoster ophthalmicus following recombinant zoster vaccine: A case report and brief literature review.
supports_node 34397201 · Journal of drugs in dermatology : JDD (2021) — Herpes Zoster Following COVID-19 Vaccination.
A6 · Differential diagnosis excludedno_data
Measure: Competing causes assessed and excluded Comparator: Likely alternative diagnoses Hit rule: Pre-specified competing causes ruled out per the working definition
Finding: No retrieved evidence assesses competing causes (differential diagnosis) for herpes zoster following shingles vaccine; the retrieved evidence describes cases of herpes zoster after COVID-19 vaccines (not shingles vaccine), pediatric vaccine-strain zoster, or conditions unrelated to this node's pair and working definition.
Case-certainty distribution (no established case definition): 1 Definite, 3 Probable, 1 Possible/unclassifiable. Transparency layer — does not change this node's status or feed C1–C6.
Cited: (none)
supporting: Shingles (zoster) vaccine Herpes zoster case report OR case series Differential diagnosis excluded pubmed · 710 hits · run 2026-09-09
mirror: Shingles (zoster) vaccine Herpes zoster alternative diagnosis OR not vaccine-related pubmed · 4069 hits · run 2026-09-09
18 retrieved record(s)
ambiguous 36650730 · The American journal of case reports (2023) — Herpes Zoster Following COVID-19 Vaccine Booster.
supports_node 28944968 · Pediatric dermatology (2017) — Pediatric vaccine-strain herpes zoster: a case series.
supports_node 34428545 · International journal of infectious dise (2021) — Herpes zoster after COVID vaccination.
ambiguous 34222134 · Clinical and experimental vaccine resear (2021) — A rare case of shingles after COVID-19 vaccine: is it a possible adverse effect?
ambiguous 25962929 · The Journal of pediatrics (2015) — Vaccine-Associated Herpes Zoster.
supports_node 39296531 · IDCases (2024) — Herpes zoster ophthalmicus following recombinant zoster vaccine: A case report and brief literature review.
ambiguous 33647971 · QJM : monthly journal of the Association (2021) — COVID-19 vaccine-related myositis.
Measure: Object recurs on a further dose Comparator: First-dose response Hit rule: Object recurs after a subsequent dose (re-exposure)
Finding: No retrieved evidence reports recurrence of herpes zoster after a subsequent (second or later) dose of shingles vaccine specifically; the closest case report describes herpes zoster after a single dose of Shingrix, not after rechallenge with a further dose.
Cited: (none)
supporting: Shingles (zoster) vaccine Herpes zoster case report OR case series Rechallenge / re-exposure pubmed · 285 hits · run 2026-09-09
mirror: Shingles (zoster) vaccine Herpes zoster alternative diagnosis OR not vaccine-related pubmed · 4069 hits · run 2026-09-09
24 retrieved record(s)
does_not_resolve 36650730 · The American journal of case reports (2023) — Herpes Zoster Following COVID-19 Vaccine Booster.
supports_node 28944968 · Pediatric dermatology (2017) — Pediatric vaccine-strain herpes zoster: a case series.
supports_node 34428545 · International journal of infectious dise (2021) — Herpes zoster after COVID vaccination.
supports_node 34222134 · Clinical and experimental vaccine resear (2021) — A rare case of shingles after COVID-19 vaccine: is it a possible adverse effect?
ambiguous 25962929 · The Journal of pediatrics (2015) — Vaccine-Associated Herpes Zoster.
supports_node 39296531 · IDCases (2024) — Herpes zoster ophthalmicus following recombinant zoster vaccine: A case report and brief literature review.
supports_node 34397201 · Journal of drugs in dermatology : JDD (2021) — Herpes Zoster Following COVID-19 Vaccination.
does_not_resolve 36752132 · Revista espanola de quimioterapia : publ (2023) — Status of Herpes Zoster and Herpes Zoster Vaccines in 2023: A position paper.
A8 · Adjudicated by criteria (no established case definition)no_data
Measure: Object adjudicated by published criteria Comparator: Published clinical / Brighton criteria Hit rule: Cases adjudicated to 'definite' by a published criterion set
Finding: The retrieved evidence includes only case reports of herpes zoster following COVID-19 vaccines, varicella vaccines, or a recombinant zoster vaccine, but no evidence specifically adjudicates cases of Herpes zoster attributed to Shingles (zoster) vaccine using a published criterion set for 'definite' cases within a pre-specified risk window.
Case-certainty distribution (no established case definition): 2 Definite, 4 Probable, 2 Possible/unclassifiable. Transparency layer — does not change this node's status or feed C1–C6.
Cited: (none)
supporting: Shingles (zoster) vaccine Herpes zoster case report OR case series Adjudicated by criteria pubmed · 322 hits · run 2026-09-09
mirror: Shingles (zoster) vaccine Herpes zoster alternative diagnosis OR not vaccine-related pubmed · 4069 hits · run 2026-09-09
23 retrieved record(s)
ambiguous 36650730 · The American journal of case reports (2023) — Herpes Zoster Following COVID-19 Vaccine Booster.
supports_node 28944968 · Pediatric dermatology (2017) — Pediatric vaccine-strain herpes zoster: a case series.
supports_node 42438029 · Internal medicine (Tokyo, Japan) (2026) — Disseminated Varicella-Zoster Virus Infection Following a Live Attenuated Varicella Vaccine (Oka Strain) in a Patient with Rheumatoid Arthritis: A Case Report.
supports_node 34428545 · International journal of infectious dise (2021) — Herpes zoster after COVID vaccination.
supports_node 34222134 · Clinical and experimental vaccine resear (2021) — A rare case of shingles after COVID-19 vaccine: is it a possible adverse effect?
ambiguous 25962929 · The Journal of pediatrics (2015) — Vaccine-Associated Herpes Zoster.
supports_node 39296531 · IDCases (2024) — Herpes zoster ophthalmicus following recombinant zoster vaccine: A case report and brief literature review.
supports_node 34397201 · Journal of drugs in dermatology : JDD (2021) — Herpes Zoster Following COVID-19 Vaccination.
A9 · Natural-history consistencyno_data
Measure: Course matches the object's natural history Comparator: Known natural history of the object Hit rule: Clinical course (onset, peak, recovery) matches the object's natural history
Finding: The retrieved evidence includes only case reports of herpes zoster after COVID-19 vaccines or after recombinant zoster vaccine (RZV), not after the Shingles (zoster) vaccine itself, and does not describe natural-history consistency (onset, peak, recovery) for herpes zoster attributed to Shingles vaccine.
Cited: (none)
supporting: Shingles (zoster) vaccine Herpes zoster case report OR case series Natural-history consistency pubmed · 386 hits · run 2026-09-09
mirror: Shingles (zoster) vaccine Herpes zoster alternative diagnosis OR not vaccine-related pubmed · 4069 hits · run 2026-09-09
18 retrieved record(s)
supports_node 36650730 · The American journal of case reports (2023) — Herpes Zoster Following COVID-19 Vaccine Booster.
supports_node 28944968 · Pediatric dermatology (2017) — Pediatric vaccine-strain herpes zoster: a case series.
ambiguous 34428545 · International journal of infectious dise (2021) — Herpes zoster after COVID vaccination.
does_not_resolve 34222134 · Clinical and experimental vaccine resear (2021) — A rare case of shingles after COVID-19 vaccine: is it a possible adverse effect?
ambiguous 25962929 · The Journal of pediatrics (2015) — Vaccine-Associated Herpes Zoster.
supports_node 39296531 · IDCases (2024) — Herpes zoster ophthalmicus following recombinant zoster vaccine: A case report and brief literature review.
does_not_resolve 33647971 · QJM : monthly journal of the Association (2021) — COVID-19 vaccine-related myositis.
Measure: Not attributable to a co-occurring condition Comparator: Co-occurring illness that could produce the object Hit rule: Object not better explained by a co-occurring condition (infection, etc.)
Finding: Case reports describe herpes zoster occurring after receipt of the recombinant zoster vaccine (Shingrix), suggesting a possible rare adverse event. No retrieved evidence directly addresses whether the occurrence is attributable to the vaccine after excluding co-occurring conditions.
supporting: Shingles (zoster) vaccine Herpes zoster case report OR case series No confounding object pubmed · 302 hits · run 2026-09-09
mirror: Shingles (zoster) vaccine Herpes zoster alternative diagnosis OR not vaccine-related pubmed · 4069 hits · run 2026-09-09
23 retrieved record(s)
supports_node 36650730 · The American journal of case reports (2023) — Herpes Zoster Following COVID-19 Vaccine Booster.
supports_node 28944968 · Pediatric dermatology (2017) — Pediatric vaccine-strain herpes zoster: a case series.
supports_node 34428545 · International journal of infectious dise (2021) — Herpes zoster after COVID vaccination.
ambiguous 34222134 · Clinical and experimental vaccine resear (2021) — A rare case of shingles after COVID-19 vaccine: is it a possible adverse effect?
ambiguous 25962929 · The Journal of pediatrics (2015) — Vaccine-Associated Herpes Zoster.
supports_node 39296531 · IDCases (2024) — Herpes zoster ophthalmicus following recombinant zoster vaccine: A case report and brief literature review.
ambiguous 34397201 · Journal of drugs in dermatology : JDD (2021) — Herpes Zoster Following COVID-19 Vaccination.
Measure: Object at the site the mechanism predicts Comparator: Predicted anatomic site from the mechanism Hit rule: Object localizes to the anatomic site the mechanism predicts
Finding: no evidence found
Cited: (none)
supporting: Shingles (zoster) vaccine Herpes zoster anatomic localization Predicted site of injury mechanism pubmed · 0 hits (0 hits — negative) · run 2026-09-09
mirror: Shingles (zoster) vaccine Herpes zoster Predicted site of injury not consistent with mechanism pubmed · 0 hits (0 hits — negative) · run 2026-09-09
D2 · Spared structuresno_data
Measure: Structures the mechanism should spare are spared Comparator: Structures predicted unaffected Hit rule: Structures predicted spared by the mechanism are indeed spared
mirror: Shingles (zoster) vaccine Herpes zoster Spared structures not consistent with mechanism pubmed · 0 hits (0 hits — negative) · run 2026-09-09
D3 · Local vs systemic distributionno_data
Measure: Distribution matches mechanism scope Comparator: Local (injection site) vs systemic expectation Hit rule: Observed distribution (local vs systemic) matches the mechanism's predicted scope
Finding: no evidence found
Cited: (none)
supporting: Shingles (zoster) vaccine Herpes zoster anatomic localization Local vs systemic distribution mechanism pubmed · 0 hits (0 hits — negative) · run 2026-09-09
mirror: Shingles (zoster) vaccine Herpes zoster Local vs systemic distribution not consistent with mechanism pubmed · 0 hits (0 hits — negative) · run 2026-09-09
D4 · Kinetics classno_data
Measure: Onset/offset kinetics match the mechanism Comparator: Expected kinetic class (acute vs chronic) Hit rule: Onset and offset kinetics are in the class the mechanism predicts
Finding: The abstract mentions pre-existing antibodies against herpes zoster virus (HZV) vaccine but does not provide any data on onset or offset kinetics of new herpes zoster attributed to the shingles vaccine.
mirror: Shingles (zoster) vaccine Herpes zoster Kinetics class not consistent with mechanism pubmed · 1 hits · run 2026-09-09
1 retrieved record(s)
refutes_node 42084498 · Human vaccines & immunotherapeutics (2026) — Effect of nipocalimab on IgG responses to vaccinations and viral infections in patients with IgG autoantibody-mediated diseases: Post hoc analyses of three rand
D5 · Platform-mechanism matchno_data
Measure: Mechanism is consistent with the platform Comparator: Mechanistic expectation for the platform Hit rule: The proposed mechanism is biologically consistent with the vaccine platform
mirror: Shingles (zoster) vaccine Herpes zoster Platform-mechanism match not consistent with mechanism pubmed · 0 hits (0 hits — negative) · run 2026-09-09
H3 · Targeted treatment reversesno_data
Measure: A targeted treatment reverses the object in patients Comparator: Treatment-naive / placebo Hit rule: A mechanism-directed treatment reverses the object (vs control treatment)
Finding: no evidence found
Cited: (none)
supporting: Shingles (zoster) vaccine Herpes zoster Targeted treatment reverses intervention OR treatment OR reversal pubmed · 15145596 hits · run 2026-09-09
mirror: Shingles (zoster) vaccine Herpes zoster Targeted treatment reverses no effect intervention pubmed · 1 hits · run 2026-09-09
1 retrieved record(s)
does_not_resolve 27348287 · Journal of managed care & specialty phar (2016) — Budget-Impact Analysis of Alternative Herpes Zoster Vaccine Strategies: A U.S. HMO Perspective.
I1 · No internal contradictionno_data
Measure: No node's finding contradicts another Comparator: Internal consistency across nodes Hit rule: No evaluated node directly contradicts another (coherence)
Finding: no evidence found
Cited: (none)
supporting: Shingles (zoster) vaccine Herpes zoster No internal contradiction coherence OR latency OR susceptibility pubmed · 870319 hits · run 2026-09-09
mirror: Shingles (zoster) vaccine Herpes zoster No internal contradiction inconsistent OR contradicts pubmed · 27616 hits · run 2026-09-09
1 retrieved record(s)
does_not_resolve 25187623 · Reproduction (Cambridge, England) (2014) — Epigenetics and life-long consequences of an adverse nutritional and diabetic intrauterine environment.
I2 · Analogy to a known objectno_data
Measure: Object analogous to a well-established analog Comparator: Established analog's profile Hit rule: The object's profile matches a well-established analog on key features
Finding: no evidence found
Cited: (none)
supporting: Shingles (zoster) vaccine Herpes zoster Analogy to a known object coherence OR latency OR susceptibility pubmed · 870319 hits · run 2026-09-09
mirror: Shingles (zoster) vaccine Herpes zoster Analogy to a known object inconsistent OR contradicts pubmed · 27616 hits · run 2026-09-09
1 retrieved record(s)
does_not_resolve 25187623 · Reproduction (Cambridge, England) (2014) — Epigenetics and life-long consequences of an adverse nutritional and diabetic intrauterine environment.
I5 · Latency coherenceno_data
Measure: Observed latency matches the mechanism's latency Comparator: Mechanism-predicted latency Hit rule: Observed onset latency is coherent with the mechanism's predicted latency
Finding: no evidence found
Cited: (none)
supporting: Shingles (zoster) vaccine Herpes zoster Latency coherence coherence OR latency OR susceptibility pubmed · 870319 hits · run 2026-09-09
mirror: Shingles (zoster) vaccine Herpes zoster Latency coherence inconsistent OR contradicts pubmed · 27617 hits · run 2026-09-09
Measure: Window/hit-rule pre-specified before data Comparator: Pre-specified vs post-hoc Hit rule: The risk window, object, and hit rule were pre-specified before data were seen
Finding: The retrieved evidence discusses the use of large language models and artificial intelligence to adjudicate immune-related adverse events and major adverse cardiovascular events, but does not address the pre-specification of risk windows or hit rules for a shingles vaccine causing herpes zoster.
Cited: (none)
supporting: Shingles (zoster) vaccine Herpes zoster Pre-specification pre-specified OR adjudicated pubmed · 13561 hits · run 2026-09-09
mirror: Shingles (zoster) vaccine Herpes zoster Pre-specification post-hoc OR hypothesis-generating only pubmed · 1712 hits · run 2026-09-09
2 retrieved record(s)
does_not_resolve 39226489 · Journal of clinical oncology : official (2024) — Enhancing Precision in Detecting Severe Immune-Related Adverse Events: Comparative Analysis of Large Language Models and International Classification of Disease
does_not_resolve 41493293 · Journal of the American College of Cardi (2026) — Using Artificial Intelligence to Adjudicate Major Adverse Cardiovascular Events in Clinical Trials.
J2 · Contrary-evidence logno_data
Measure: Contrary evidence is logged, not omitted Comparator: Support-only dossier Hit rule: Contrary / null / refuting findings are logged and shown alongside support
Finding: The retrieved evidence discusses the use of large language models and ICD codes to detect immune-related adverse events from immune checkpoint inhibitors, and AI adjudication of major adverse cardiovascular events in clinical trials. Neither publication addresses Shingles (zoster) vaccine or herpes zoster as an adverse event following vaccination.
Cited: (none)
supporting: Shingles (zoster) vaccine Herpes zoster Contrary-evidence log pre-specified OR adjudicated pubmed · 13561 hits · run 2026-09-09
mirror: Shingles (zoster) vaccine Herpes zoster Contrary-evidence log post-hoc OR hypothesis-generating only pubmed · 1712 hits · run 2026-09-09
2 retrieved record(s)
does_not_resolve 39226489 · Journal of clinical oncology : official (2024) — Enhancing Precision in Detecting Severe Immune-Related Adverse Events: Comparative Analysis of Large Language Models and International Classification of Disease
does_not_resolve 41493293 · Journal of the American College of Cardi (2026) — Using Artificial Intelligence to Adjudicate Major Adverse Cardiovascular Events in Clinical Trials.
J3 · No temporality-only claimno_data
Measure: Claim not based on temporality alone Comparator: Sequence-only evidence Hit rule: The claim is not supported by temporal sequence alone (independent evidence exists)
Finding: no evidence found
Cited: (none)
supporting: Shingles (zoster) vaccine Herpes zoster No temporality-only claim pre-specified OR adjudicated pubmed · 13561 hits · run 2026-09-09
mirror: Shingles (zoster) vaccine Herpes zoster No temporality-only claim post-hoc OR hypothesis-generating only pubmed · 1713 hits · run 2026-09-09
2 retrieved record(s)
does_not_resolve 39226489 · Journal of clinical oncology : official (2024) — Enhancing Precision in Detecting Severe Immune-Related Adverse Events: Comparative Analysis of Large Language Models and International Classification of Disease
does_not_resolve 41493293 · Journal of the American College of Cardi (2026) — Using Artificial Intelligence to Adjudicate Major Adverse Cardiovascular Events in Clinical Trials.
J4 · Passive-surveillance roleno_data
Measure: Passive-surveillance findings bounded correctly Comparator: Active-surveillance confirmation Hit rule: Passive-surveillance signals are framed as hypothesis-generating, not confirmatory
Finding: no evidence found
Cited: (none)
supporting: Shingles (zoster) vaccine Herpes zoster Passive-surveillance role pre-specified OR adjudicated pubmed · 13561 hits · run 2026-09-09
mirror: Shingles (zoster) vaccine Herpes zoster Passive-surveillance role post-hoc OR hypothesis-generating only pubmed · 1712 hits · run 2026-09-09
1 retrieved record(s)
does_not_resolve 39226489 · Journal of clinical oncology : official (2024) — Enhancing Precision in Detecting Severe Immune-Related Adverse Events: Comparative Analysis of Large Language Models and International Classification of Disease
J5 · Dose mappingno_data
Measure: Dose/lot exposure mapped to the object Comparator: Unmapped exposure Hit rule: Dose / lot exposure is mapped to the object where the mechanism predicts it
Finding: The retrieved evidence discusses using large language models to identify immune-related adverse events from immune checkpoint inhibitor therapy and adjudicating major adverse cardiovascular events in clinical trials; neither article addresses dose/lot exposure mapping for shingles vaccine and herpes zoster.
Cited: (none)
supporting: Shingles (zoster) vaccine Herpes zoster Dose mapping pre-specified OR adjudicated pubmed · 13561 hits · run 2026-09-09
mirror: Shingles (zoster) vaccine Herpes zoster Dose mapping post-hoc OR hypothesis-generating only pubmed · 1712 hits · run 2026-09-09
2 retrieved record(s)
does_not_resolve 39226489 · Journal of clinical oncology : official (2024) — Enhancing Precision in Detecting Severe Immune-Related Adverse Events: Comparative Analysis of Large Language Models and International Classification of Disease
does_not_resolve 41493293 · Journal of the American College of Cardi (2026) — Using Artificial Intelligence to Adjudicate Major Adverse Cardiovascular Events in Clinical Trials.
Epidemiologic chassis 13/13 evaluated
B1 · Excess vs baselinesupports
Measure: RR/IRR vs unexposed or prior window Comparator: Unvaccinated person-time or pre-vaccination window Hit rule: RR/IRR > 1 with CI excluding 1 after pre-specified confounders
Finding: PMID 40924159 reports a transient increased risk of shingles (Herpes zoster) shortly after Shingrix vaccination using self-controlled case series analysis, with a 21-day risk window and RR/IRR > 1 with CI excluding 1, though the exact effect size is not given in the abstract.
supporting: Shingles (zoster) vaccine Herpes zoster Excess vs baseline incidence risk cohort OR self-controlled case series pubmed · 948 hits · run 2026-09-09
mirror: Shingles (zoster) vaccine Herpes zoster no association OR null OR no increased risk Excess vs baseline pubmed · 89551 hits · run 2026-09-09
16 retrieved record(s)
does_not_resolve 34937500 · Expert review of vaccines (2022) — Self-controlled case series design in vaccine safety: a systematic review.
does_not_resolve 35489031 · Journal of clinical psychopharmacology (2022) — Prescription Stimulants and the Risk of Psychosis: A Systematic Review of Observational Studies.
does_not_resolve 30851046 · Biostatistics (Oxford, England) (2020) — ConvSCCS: convolutional self-controlled case series model for lagged adverse event detection.
does_not_resolve 40664645 · Nature communications (2025) — Evaluating the safety of XBB.1.5-containing COVID-19 mRNA vaccines using a self-controlled case series study.
does_not_resolve 35215786 · Viruses (2022) — Herpes zoster: A Review of Clinical Manifestations and Management.
does_not_resolve 39053634 · Nature medicine (2024) — The recombinant shingles vaccine is associated with lower risk of dementia.
does_not_resolve 38687552 · Brain and behavior (2024) — Herpes zoster vaccination and the risk of dementia: A systematic review and meta-analysis.
B2 · SCCSsupports
Measure: Self-controlled case series risk ratio Comparator: Individuals' own risk intervals (no-event) Hit rule: SCCS risk ratio > 1 in the post-vaccination window, CI excluding 1
Finding: One self-controlled case series study (PMID 40924159) reported a transient increased risk of shingles in the 21 days post-Shingrix vaccination, with a risk ratio > 1 and a 95% CI excluding 1, meeting the hit rule for node B2.
supporting: Shingles (zoster) vaccine Herpes zoster SCCS incidence risk cohort OR self-controlled case series pubmed · 948 hits · run 2026-09-09
mirror: Shingles (zoster) vaccine Herpes zoster no association OR null OR no increased risk SCCS pubmed · 89657 hits · run 2026-09-09
16 retrieved record(s)
does_not_resolve 34937500 · Expert review of vaccines (2022) — Self-controlled case series design in vaccine safety: a systematic review.
does_not_resolve 35489031 · Journal of clinical psychopharmacology (2022) — Prescription Stimulants and the Risk of Psychosis: A Systematic Review of Observational Studies.
does_not_resolve 30851046 · Biostatistics (Oxford, England) (2020) — ConvSCCS: convolutional self-controlled case series model for lagged adverse event detection.
does_not_resolve 40664645 · Nature communications (2025) — Evaluating the safety of XBB.1.5-containing COVID-19 mRNA vaccines using a self-controlled case series study.
ambiguous 35215786 · Viruses (2022) — Herpes zoster: A Review of Clinical Manifestations and Management.
does_not_resolve 39053634 · Nature medicine (2024) — The recombinant shingles vaccine is associated with lower risk of dementia.
does_not_resolve 38687552 · Brain and behavior (2024) — Herpes zoster vaccination and the risk of dementia: A systematic review and meta-analysis.
B3 · Cohort / risk-intervalsupports
Measure: Incidence rate ratio in defined window Comparator: Pre-specified risk vs comparison interval Hit rule: IRR > 1 in the pre-specified window, CI excluding 1, stratified by age/sex
Finding: PMID 40924159 reports a transient increased risk of shingles (Herpes zoster) in the 21-day risk window following Shingrix vaccination using self-controlled case series analysis, with IRR > 1 and confidence intervals excluding 1, stratified by age.
supporting: Shingles (zoster) vaccine Herpes zoster Cohort / risk-interval incidence risk cohort OR self-controlled case series pubmed · 950 hits · run 2026-09-09
mirror: Shingles (zoster) vaccine Herpes zoster no association OR null OR no increased risk Cohort / risk-interval pubmed · 89158 hits · run 2026-09-09
15 retrieved record(s)
does_not_resolve 34937500 · Expert review of vaccines (2022) — Self-controlled case series design in vaccine safety: a systematic review.
does_not_resolve 35489031 · Journal of clinical psychopharmacology (2022) — Prescription Stimulants and the Risk of Psychosis: A Systematic Review of Observational Studies.
does_not_resolve 30851046 · Biostatistics (Oxford, England) (2020) — ConvSCCS: convolutional self-controlled case series model for lagged adverse event detection.
does_not_resolve 40664645 · Nature communications (2025) — Evaluating the safety of XBB.1.5-containing COVID-19 mRNA vaccines using a self-controlled case series study.
does_not_resolve 35215786 · Viruses (2022) — Herpes zoster: A Review of Clinical Manifestations and Management.
does_not_resolve 39053634 · Nature medicine (2024) — The recombinant shingles vaccine is associated with lower risk of dementia.
does_not_resolve 38687552 · Brain and behavior (2024) — Herpes zoster vaccination and the risk of dementia: A systematic review and meta-analysis.
B4 · Meta-analysis / poolingno_data
Measure: Pooled effect across studies Comparator: Pooled estimate with heterogeneity Hit rule: Pooled estimate > 1 (or < 1) with quantified heterogeneity (I2)
Finding: The retrieved evidence includes a systematic review and meta-analysis [PMID 39585863 2024] that pooled efficacy data for recombinant zoster vaccine in immunocompromised populations, but no pooled estimate with quantified heterogeneity (I²) for the pair 'Shingles (zoster) vaccine -> Herpes zoster' was identified. Other retrieved studies either examine dementia risk (not herpes zoster outcomes after vaccination) or focus on diabetes as a risk factor for herpes zoster, not vaccine-related adverse events.
Cited: (none)
supporting: Shingles (zoster) vaccine Herpes zoster Meta-analysis / pooling incidence risk cohort OR self-controlled case series pubmed · 955 hits · run 2026-09-09
mirror: Shingles (zoster) vaccine Herpes zoster no association OR null OR no increased risk Meta-analysis / pooling pubmed · 112995 hits · run 2026-09-09
15 retrieved record(s)
does_not_resolve 38687552 · Brain and behavior (2024) — Herpes zoster vaccination and the risk of dementia: A systematic review and meta-analysis.
does_not_resolve 34536279 · The Journal of clinical endocrinology an (2022) — Association Between Diabetes Mellitus and the Risk of Herpes Zoster: A Systematic Review and Meta-analysis.
does_not_resolve 36098300 · The lancet. Healthy longevity (2022) — Post-licensure zoster vaccine effectiveness against herpes zoster and postherpetic neuralgia in older adults: a systematic review and meta-analysis.
does_not_resolve 40551502 · Journal of Alzheimer's disease : JAD (2025) — The association between herpes zoster vaccination and the decreased risk of dementia: A systematic review and meta-analysis of cohort studies.
does_not_resolve 34937500 · Expert review of vaccines (2022) — Self-controlled case series design in vaccine safety: a systematic review.
does_not_resolve 35215786 · Viruses (2022) — Herpes zoster: A Review of Clinical Manifestations and Management.
does_not_resolve 42296498 · Annals of internal medicine (2026) — Dementia Risk After Recombinant Herpes Zoster Vaccination in Older Adults With a Recent Skilled-Nursing Facility Stay : A Target Trial Emulation.
B5 · Negative-control outcomesrefutes
Measure: No excess for outcomes the vaccine should not cause Comparator: Negative-control outcomes (unaffected by mechanism) Hit rule: Null for negative-control outcomes while target outcome is positive (specificity)
Finding: The retrieved evidence includes a self-controlled case series analysis [PMID 40924159] reporting a transient increased risk of shingles (Herpes zoster) shortly after Shingrix vaccination, indicating a positive association rather than a null finding for this negative-control outcome.
supporting: Shingles (zoster) vaccine Herpes zoster Negative-control outcomes incidence risk cohort OR self-controlled case series pubmed · 949 hits · run 2026-09-09
mirror: Shingles (zoster) vaccine Herpes zoster no association OR null OR no increased risk Negative-control outcomes pubmed · 89362 hits · run 2026-09-09
16 retrieved record(s)
does_not_resolve 34937500 · Expert review of vaccines (2022) — Self-controlled case series design in vaccine safety: a systematic review.
does_not_resolve 35489031 · Journal of clinical psychopharmacology (2022) — Prescription Stimulants and the Risk of Psychosis: A Systematic Review of Observational Studies.
does_not_resolve 30851046 · Biostatistics (Oxford, England) (2020) — ConvSCCS: convolutional self-controlled case series model for lagged adverse event detection.
does_not_resolve 40664645 · Nature communications (2025) — Evaluating the safety of XBB.1.5-containing COVID-19 mRNA vaccines using a self-controlled case series study.
ambiguous 35215786 · Viruses (2022) — Herpes zoster: A Review of Clinical Manifestations and Management.
does_not_resolve 39053634 · Nature medicine (2024) — The recombinant shingles vaccine is associated with lower risk of dementia.
does_not_resolve 38687552 · Brain and behavior (2024) — Herpes zoster vaccination and the risk of dementia: A systematic review and meta-analysis.
B6 · Other-antigen comparisonno_data
Measure: Risk vs a different-antigen comparator Comparator: Comparator product with a different antigen Hit rule: Risk specific to the target antigen, not shared with the comparator antigen
Finding: No evidence was retrieved that directly addresses the risk of new Herpes zoster attributed to Shingles vaccine using a different-antigen comparator (Node B6). The retrieved evidence includes studies on self-controlled case series methodology and on herpes zoster risk after Shingrix vaccination, but none compare the target antigen against a different-antigen comparator.
Cited: (none)
supporting: Shingles (zoster) vaccine Herpes zoster Other-antigen comparison incidence risk cohort OR self-controlled case series pubmed · 948 hits · run 2026-09-09
mirror: Shingles (zoster) vaccine Herpes zoster no association OR null OR no increased risk Other-antigen comparison pubmed · 89124 hits · run 2026-09-09
15 retrieved record(s)
does_not_resolve 34937500 · Expert review of vaccines (2022) — Self-controlled case series design in vaccine safety: a systematic review.
does_not_resolve 30851046 · Biostatistics (Oxford, England) (2020) — ConvSCCS: convolutional self-controlled case series model for lagged adverse event detection.
does_not_resolve 40664645 · Nature communications (2025) — Evaluating the safety of XBB.1.5-containing COVID-19 mRNA vaccines using a self-controlled case series study.
does_not_resolve 35215786 · Viruses (2022) — Herpes zoster: A Review of Clinical Manifestations and Management.
does_not_resolve 42296498 · Annals of internal medicine (2026) — Dementia Risk After Recombinant Herpes Zoster Vaccination in Older Adults With a Recent Skilled-Nursing Facility Stay : A Target Trial Emulation.
does_not_resolve 39053634 · Nature medicine (2024) — The recombinant shingles vaccine is associated with lower risk of dementia.
does_not_resolve 38687552 · Brain and behavior (2024) — Herpes zoster vaccination and the risk of dementia: A systematic review and meta-analysis.
B7 · Absolute risksupports
Measure: Per-100k risk in window Comparator: Absolute incidence per 100k Hit rule: Absolute risk reported and stable across the window (not an artifact of rarity)
Finding: PMID 40924159 provides evidence from a self-controlled case series analysis showing a transient increased risk of herpes zoster within 21 days post-Shingrix vaccination; absolute risk per 100,000 in the window is not reported, though the study design and risk window support the candidate definition of new herpes zoster attributed to the vaccine within a specified risk window.
supporting: Shingles (zoster) vaccine Herpes zoster Absolute risk incidence risk cohort OR self-controlled case series pubmed · 951 hits · run 2026-09-09
mirror: Shingles (zoster) vaccine Herpes zoster no association OR null OR no increased risk Absolute risk pubmed · 112408 hits · run 2026-09-09
16 retrieved record(s)
does_not_resolve 37574727 · Journal of Alzheimer's disease : JAD (2023) — The Impact of Routine Vaccinations on Alzheimer's Disease Risk in Persons 65 Years and Older: A Claims-Based Cohort Study using Propensity Score Matching.
does_not_resolve 34937500 · Expert review of vaccines (2022) — Self-controlled case series design in vaccine safety: a systematic review.
does_not_resolve 35489031 · Journal of clinical psychopharmacology (2022) — Prescription Stimulants and the Risk of Psychosis: A Systematic Review of Observational Studies.
ambiguous 30851046 · Biostatistics (Oxford, England) (2020) — ConvSCCS: convolutional self-controlled case series model for lagged adverse event detection.
ambiguous 35215786 · Viruses (2022) — Herpes zoster: A Review of Clinical Manifestations and Management.
does_not_resolve 42296498 · Annals of internal medicine (2026) — Dementia Risk After Recombinant Herpes Zoster Vaccination in Older Adults With a Recent Skilled-Nursing Facility Stay : A Target Trial Emulation.
does_not_resolve 39053634 · Nature medicine (2024) — The recombinant shingles vaccine is associated with lower risk of dementia.
B8 · Platform splitsupports
Measure: Risk by vaccine platform / product Comparator: Platform (mRNA vs viral vector, etc.) Hit rule: Risk attributable to a specific platform, not to 'a vaccine' generally
Finding: PMID 40924159 reports a transient increased risk of shingles (Herpes zoster) within 21 days post-RZV (Shingrix) vaccination in a self-controlled case series analysis, providing evidence for a platform-specific risk (recombinant vaccine).
supporting: Shingles (zoster) vaccine Herpes zoster Platform split incidence risk cohort OR self-controlled case series pubmed · 948 hits · run 2026-09-09
mirror: Shingles (zoster) vaccine Herpes zoster no association OR null OR no increased risk Platform split pubmed · 89189 hits · run 2026-09-09
16 retrieved record(s)
does_not_resolve 34937500 · Expert review of vaccines (2022) — Self-controlled case series design in vaccine safety: a systematic review.
does_not_resolve 35489031 · Journal of clinical psychopharmacology (2022) — Prescription Stimulants and the Risk of Psychosis: A Systematic Review of Observational Studies.
does_not_resolve 30851046 · Biostatistics (Oxford, England) (2020) — ConvSCCS: convolutional self-controlled case series model for lagged adverse event detection.
does_not_resolve 40664645 · Nature communications (2025) — Evaluating the safety of XBB.1.5-containing COVID-19 mRNA vaccines using a self-controlled case series study.
does_not_resolve 35215786 · Viruses (2022) — Herpes zoster: A Review of Clinical Manifestations and Management.
does_not_resolve 42296498 · Annals of internal medicine (2026) — Dementia Risk After Recombinant Herpes Zoster Vaccination in Older Adults With a Recent Skilled-Nursing Facility Stay : A Target Trial Emulation.
does_not_resolve 39053634 · Nature medicine (2024) — The recombinant shingles vaccine is associated with lower risk of dementia.
B9 · Host-structure stratificationsupports
Measure: Risk by age / sex / host structure Comparator: Unstratified estimate Hit rule: Risk concentrated in a defined host subgroup (e.g. young males), stable across sources
Finding: PMID 40924159 directly reports an increased risk of shingles (herpes zoster) immediately following Shingrix vaccination in adults ≥65 years, with risk stratified by age (<65 and ≥65) and stable across two independent datasets, supporting risk concentration in older adults as a defined host subgroup.
supporting: Shingles (zoster) vaccine Herpes zoster Host-structure stratification incidence risk cohort OR self-controlled case series pubmed · 948 hits · run 2026-09-09
mirror: Shingles (zoster) vaccine Herpes zoster no association OR null OR no increased risk Host-structure stratification pubmed · 89122 hits · run 2026-09-09
16 retrieved record(s)
does_not_resolve 34937500 · Expert review of vaccines (2022) — Self-controlled case series design in vaccine safety: a systematic review.
does_not_resolve 35489031 · Journal of clinical psychopharmacology (2022) — Prescription Stimulants and the Risk of Psychosis: A Systematic Review of Observational Studies.
does_not_resolve 30851046 · Biostatistics (Oxford, England) (2020) — ConvSCCS: convolutional self-controlled case series model for lagged adverse event detection.
refutes_node 40664645 · Nature communications (2025) — Evaluating the safety of XBB.1.5-containing COVID-19 mRNA vaccines using a self-controlled case series study.
does_not_resolve 35215786 · Viruses (2022) — Herpes zoster: A Review of Clinical Manifestations and Management.
does_not_resolve 39053634 · Nature medicine (2024) — The recombinant shingles vaccine is associated with lower risk of dementia.
does_not_resolve 38687552 · Brain and behavior (2024) — Herpes zoster vaccination and the risk of dementia: A systematic review and meta-analysis.
B10 · Formulation / component changesupports
Measure: Risk tracks a formulation change Comparator: Pre- vs post-change formulation Hit rule: Risk change tracks a documented formulation / component change over time
Finding: PMID 40924159 (2025) directly addresses the node by documenting a transient increased risk of shingles (Herpes zoster) following recombinant shingles vaccine (RZV; Shingrix) administration in Australia, using a self-controlled case series design and a 21-day post-vaccination risk window. This evidence supports that risk tracks a formulation change (live zoster vaccine to recombinant RZV), as the observed risk increase is temporally associated with introduction of the new recombinant vaccine formulation.
supporting: Shingles (zoster) vaccine Herpes zoster Formulation / component change incidence risk cohort OR self-controlled case series pubmed · 948 hits · run 2026-09-09
mirror: Shingles (zoster) vaccine Herpes zoster no association OR null OR no increased risk Formulation / component change pubmed · 89284 hits · run 2026-09-09
15 retrieved record(s)
does_not_resolve 34937500 · Expert review of vaccines (2022) — Self-controlled case series design in vaccine safety: a systematic review.
does_not_resolve 30851046 · Biostatistics (Oxford, England) (2020) — ConvSCCS: convolutional self-controlled case series model for lagged adverse event detection.
does_not_resolve 40664645 · Nature communications (2025) — Evaluating the safety of XBB.1.5-containing COVID-19 mRNA vaccines using a self-controlled case series study.
ambiguous 35215786 · Viruses (2022) — Herpes zoster: A Review of Clinical Manifestations and Management.
does_not_resolve 39053634 · Nature medicine (2024) — The recombinant shingles vaccine is associated with lower risk of dementia.
does_not_resolve 38687552 · Brain and behavior (2024) — Herpes zoster vaccination and the risk of dementia: A systematic review and meta-analysis.
does_not_resolve 23863052 · The New England journal of medicine (2013) — Clinical practice: Herpes zoster.
H2 · Formulation natural experimentno_data
Measure: Risk shifts with a formulation change in the field Comparator: Pre- vs post-change formulation Hit rule: Observed risk tracks a real-world formulation change (natural experiment)
Finding: no evidence found
Cited: (none)
supporting: Shingles (zoster) vaccine Herpes zoster Formulation natural experiment intervention OR treatment OR reversal pubmed · 15145596 hits · run 2026-09-09
Measure: Risk signal appears/disappears across a pause or policy change Comparator: Pre- vs post-pause period Hit rule: The signal appears or disappears coherently with a rollout / pause (H4)
Finding: no evidence found
Cited: (none)
supporting: Shingles (zoster) vaccine Herpes zoster Policy / pause signal intervention OR treatment OR reversal pubmed · 15145596 hits · run 2026-09-09
mirror: Shingles (zoster) vaccine Herpes zoster Policy / pause signal no effect intervention pubmed · 0 hits (0 hits — negative) · run 2026-09-09
I3 · Infection coherenceno_data
Measure: Pattern is coherent with or distinct from infection Comparator: Infection-matched comparison Hit rule: The post-vaccine pattern is coherent with (or clearly distinct from) the infection pattern
Finding: The retrieved evidence includes a review (PMID 37573820) that discusses vaccine efficacy and safety but does not address whether the post-vaccine pattern of herpes zoster is coherent with or distinct from natural infection patterns. PMID 32491711 provides no abstract and no relevant content.
Cited: (none)
supporting: Shingles (zoster) vaccine Herpes zoster Infection coherence coherence OR latency OR susceptibility pubmed · 870323 hits · run 2026-09-09
mirror: Shingles (zoster) vaccine Herpes zoster Infection coherence inconsistent OR contradicts pubmed · 27617 hits · run 2026-09-09
does_not_resolve 37573820 · Atencion primaria (2023) — [Vaccination against the herpes zoster virus].
Mediator & biological gradient 24/24 evaluated
C1n · Dose strength gradientno_data
Measure: Risk vs dose strength (dose size) Comparator: Lower dose strength Hit rule: Monotonic dose-response in dose strength (larger dose -> higher risk)
Finding: No retrieved evidence addresses a monotonic dose-response in dose strength (dose size) for the Shingles (zoster) vaccine and risk of Herpes zoster. The retrieved studies focus on vaccine effectiveness, dementia risk, safety, and other outcomes, not on a dose-strength gradient.
Cited: (none)
supporting: Shingles (zoster) vaccine Herpes zoster Dose strength gradient dose-response OR dose effect pubmed · 1299405 hits · run 2026-09-09
mirror: Shingles (zoster) vaccine Herpes zoster no dose effect OR no dose-response Dose strength gradient pubmed · 512 hits · run 2026-09-09
12 retrieved record(s)
does_not_resolve 39082700 · The Journal of infectious diseases (2025) — Effectiveness of MenB-4C Vaccine Against Gonorrhea: A Systematic Review and Meta-analysis.
does_not_resolve 42296498 · Annals of internal medicine (2026) — Dementia Risk After Recombinant Herpes Zoster Vaccination in Older Adults With a Recent Skilled-Nursing Facility Stay : A Target Trial Emulation.
does_not_resolve 39733478 · Vaccine (2025) — Recombinant zoster vaccine and the risk of dementia.
refutes_node 38190712 · Annals of internal medicine (2024) — Effectiveness of Recombinant Zoster Vaccine Against Herpes Zoster in a Real-World Setting.
supports_node 38358762 · JAMA ophthalmology (2024) — Risk of Herpes Zoster Ophthalmicus Recurrence After Recombinant Zoster Vaccination.
does_not_resolve 37967254 · Human vaccines & immunotherapeutics (2023) — Effectiveness and safety of recombinant zoster vaccine: A review of real-world evidence.
refutes_node 39585863 · PloS one (2024) — Systematic review and meta-analysis of recombinant herpes zoster vaccine in immunocompromised populations.
does_not_resolve 33580242 · Clinical infectious diseases : an offici (2021) — Recombinant Zoster Vaccine (Shingrix): Real-World Effectiveness in the First 2 Years Post-Licensure.
C2n · Dose number gradientno_data
Measure: Risk vs dose number (1st vs 2nd vs 3rd) Comparator: First dose Hit rule: Risk increases (or shows a defined pattern) with dose number
Finding: no evidence found
Cited: (none)
supporting: Shingles (zoster) vaccine Herpes zoster Dose number gradient dose-response OR dose effect pubmed · 1299405 hits · run 2026-09-09
mirror: Shingles (zoster) vaccine Herpes zoster no dose effect OR no dose-response Dose number gradient pubmed · 956 hits · run 2026-09-09
13 retrieved record(s)
does_not_resolve 39082700 · The Journal of infectious diseases (2025) — Effectiveness of MenB-4C Vaccine Against Gonorrhea: A Systematic Review and Meta-analysis.
does_not_resolve 39733478 · Vaccine (2025) — Recombinant zoster vaccine and the risk of dementia.
does_not_resolve 38190712 · Annals of internal medicine (2024) — Effectiveness of Recombinant Zoster Vaccine Against Herpes Zoster in a Real-World Setting.
supports_node 38358762 · JAMA ophthalmology (2024) — Risk of Herpes Zoster Ophthalmicus Recurrence After Recombinant Zoster Vaccination.
does_not_resolve 37967254 · Human vaccines & immunotherapeutics (2023) — Effectiveness and safety of recombinant zoster vaccine: A review of real-world evidence.
does_not_resolve 39585863 · PloS one (2024) — Systematic review and meta-analysis of recombinant herpes zoster vaccine in immunocompromised populations.
ambiguous 35696161 · JAMA internal medicine (2022) — Comparative Safety of BNT162b2 and mRNA-1273 Vaccines in a Nationwide Cohort of US Veterans.
refutes_node 38682607 · Journal of medical virology (2024) — A systematic review and meta-analysis of herpes zoster occurrence/recurrence after COVID-19 infection and vaccination.
C3n · Measured-exposure tertilesno_data
Measure: Risk vs measured exposure tertile Comparator: Lowest-exposure tertile Hit rule: Risk ordered by measured-exposure tertile (high > mid > low)
Finding: no evidence found
Cited: (none)
supporting: Shingles (zoster) vaccine Herpes zoster Measured-exposure tertiles dose-response OR dose effect pubmed · 1299405 hits · run 2026-09-09
mirror: Shingles (zoster) vaccine Herpes zoster no dose effect OR no dose-response Measured-exposure tertiles pubmed · 401 hits · run 2026-09-09
13 retrieved record(s)
does_not_resolve 39082700 · The Journal of infectious diseases (2025) — Effectiveness of MenB-4C Vaccine Against Gonorrhea: A Systematic Review and Meta-analysis.
does_not_resolve 39733478 · Vaccine (2025) — Recombinant zoster vaccine and the risk of dementia.
refutes_node 38190712 · Annals of internal medicine (2024) — Effectiveness of Recombinant Zoster Vaccine Against Herpes Zoster in a Real-World Setting.
supports_node 38358762 · JAMA ophthalmology (2024) — Risk of Herpes Zoster Ophthalmicus Recurrence After Recombinant Zoster Vaccination.
does_not_resolve 37967254 · Human vaccines & immunotherapeutics (2023) — Effectiveness and safety of recombinant zoster vaccine: A review of real-world evidence.
does_not_resolve 39585863 · PloS one (2024) — Systematic review and meta-analysis of recombinant herpes zoster vaccine in immunocompromised populations.
ambiguous 35696161 · JAMA internal medicine (2022) — Comparative Safety of BNT162b2 and mRNA-1273 Vaccines in a Nationwide Cohort of US Veterans.
refutes_node 38682607 · Journal of medical virology (2024) — A systematic review and meta-analysis of herpes zoster occurrence/recurrence after COVID-19 infection and vaccination.
C4n · Organoid concentration curveno_data
Measure: Effect vs antigen concentration in organoid Comparator: Vehicle / zero antigen Hit rule: Dose-dependent effect across a graded concentration curve
Finding: no evidence found
Cited: (none)
supporting: Shingles (zoster) vaccine Herpes zoster Organoid concentration curve dose-response OR dose effect pubmed · 1299405 hits · run 2026-09-09
mirror: Shingles (zoster) vaccine Herpes zoster no dose effect OR no dose-response Organoid concentration curve pubmed · 412 hits · run 2026-09-09
13 retrieved record(s)
does_not_resolve 39082700 · The Journal of infectious diseases (2025) — Effectiveness of MenB-4C Vaccine Against Gonorrhea: A Systematic Review and Meta-analysis.
does_not_resolve 39733478 · Vaccine (2025) — Recombinant zoster vaccine and the risk of dementia.
does_not_resolve 38190712 · Annals of internal medicine (2024) — Effectiveness of Recombinant Zoster Vaccine Against Herpes Zoster in a Real-World Setting.
supports_node 38358762 · JAMA ophthalmology (2024) — Risk of Herpes Zoster Ophthalmicus Recurrence After Recombinant Zoster Vaccination.
does_not_resolve 37967254 · Human vaccines & immunotherapeutics (2023) — Effectiveness and safety of recombinant zoster vaccine: A review of real-world evidence.
refutes_node 39585863 · PloS one (2024) — Systematic review and meta-analysis of recombinant herpes zoster vaccine in immunocompromised populations.
ambiguous 35696161 · JAMA internal medicine (2022) — Comparative Safety of BNT162b2 and mRNA-1273 Vaccines in a Nationwide Cohort of US Veterans.
refutes_node 38682607 · Journal of medical virology (2024) — A systematic review and meta-analysis of herpes zoster occurrence/recurrence after COVID-19 infection and vaccination.
C5n · EC50 vs Cmax coherenceno_data
Measure: Measured exposure reaches effect threshold Comparator: Pharmacokinetic Cmax vs EC50 Hit rule: Achieved exposure (Cmax/tissue) plausibly reaches the in-vitro EC50
Finding: no evidence found
Cited: (none)
supporting: Shingles (zoster) vaccine Herpes zoster EC50 vs Cmax coherence dose-response OR dose effect pubmed · 1299405 hits · run 2026-09-09
mirror: Shingles (zoster) vaccine Herpes zoster no dose effect OR no dose-response EC50 vs Cmax coherence pubmed · 401 hits · run 2026-09-09
13 retrieved record(s)
does_not_resolve 39082700 · The Journal of infectious diseases (2025) — Effectiveness of MenB-4C Vaccine Against Gonorrhea: A Systematic Review and Meta-analysis.
does_not_resolve 42296498 · Annals of internal medicine (2026) — Dementia Risk After Recombinant Herpes Zoster Vaccination in Older Adults With a Recent Skilled-Nursing Facility Stay : A Target Trial Emulation.
does_not_resolve 39733478 · Vaccine (2025) — Recombinant zoster vaccine and the risk of dementia.
does_not_resolve 38190712 · Annals of internal medicine (2024) — Effectiveness of Recombinant Zoster Vaccine Against Herpes Zoster in a Real-World Setting.
supports_node 38358762 · JAMA ophthalmology (2024) — Risk of Herpes Zoster Ophthalmicus Recurrence After Recombinant Zoster Vaccination.
does_not_resolve 37967254 · Human vaccines & immunotherapeutics (2023) — Effectiveness and safety of recombinant zoster vaccine: A review of real-world evidence.
does_not_resolve 39585863 · PloS one (2024) — Systematic review and meta-analysis of recombinant herpes zoster vaccine in immunocompromised populations.
refutes_node 38682607 · Journal of medical virology (2024) — A systematic review and meta-analysis of herpes zoster occurrence/recurrence after COVID-19 infection and vaccination.
E1 · Mediator identified in casesno_data
Measure: Mediator present in affected tissue/cells Comparator: Unaffected tissue / control Hit rule: The hypothesized mediator is detected in the affected compartment and not (or less) in control
Finding: No retrieved evidence directly addresses detection of a hypothesized mediator (e.g., VZV or vaccine-related antigen) in affected tissue or cells of herpes zoster cases attributed to the shingles vaccine; the studies focus on vaccine efficacy, safety, or epidemiology of herpes zoster without testing a mediator in affected compartments.
Cited: (none)
supporting: Shingles (zoster) vaccine Herpes zoster mechanism Mediator identified in cases in vitro OR patient-derived pubmed · 29262 hits · run 2026-09-09
mirror: Shingles (zoster) vaccine Herpes zoster Mediator identified in cases not associated mechanism pubmed · 11 hits · run 2026-09-09
9 retrieved record(s)
refutes_node 31287523 · JAMA (2019) — Effect of Recombinant Zoster Vaccine on Incidence of Herpes Zoster After Autologous Stem Cell Transplantation: A Randomized Clinical Trial.
refutes_node 40780591 · The Journal of infection (2025) — Herpes zoster recurrence, and safety and immunogenicity of the recombinant zoster vaccine in adults aged ≥50 years with a history of herpes zoster: A phase 3, r
refutes_node 41081504 · Journal of medical virology (2025) — Epidemiology and Clinical Profile of Herpes Zoster in the Varicella Vaccine Era: A Case Series Study.
does_not_resolve 31897892 · Digestive diseases and sciences (2020) — Safety of Recombinant Zoster Vaccine in Patients with Inflammatory Bowel Disease.
does_not_resolve 28162821 · Vaccine (2017) — Safety of live vaccinations on immunosuppressive therapy in patients with immune-mediated inflammatory diseases, solid organ transplantation or after bone-marro
does_not_resolve 25419615 · JAMA neurology (2015) — Varicella-zoster virus infections in patients treated with fingolimod: risk assessment and consensus recommendations for management.
does_not_resolve 42194695 · Journal of clinical medicine (2026) — Herpes Zoster in Patients Treated with JAK Inhibitors for Immune-Mediated Inflammatory Diseases: Incidence, Associated Factors and Vaccination Uptake in a Real-
supports_node 37148041 · Neurology India (2023) — Spectrum of Serious Neurological and Psychiatric Adverse Events in Indian COVID-19 Vaccine Recipients: A Systematic Review of Case Reports and Case Series.
E2 · Mediator in healthy vaccineesno_data
Measure: Mediator detectable after vaccination Comparator: Pre-vaccination baseline Hit rule: Mediator appears after vaccination and tracks the exposure window
Finding: The retrieved study assessed a live attenuated varicella vaccine (not the shingles vaccine) in HIV-infected adults, not healthy vaccinees, and did not report new Herpes zoster cases attributed to vaccination; no evidence directly addresses a mediator for the E2 node in healthy vaccinees.
Cited: (none)
supporting: Shingles (zoster) vaccine Herpes zoster mechanism Mediator in healthy vaccinees in vitro OR patient-derived pubmed · 29262 hits · run 2026-09-09
mirror: Shingles (zoster) vaccine Herpes zoster Mediator in healthy vaccinees not associated mechanism pubmed · 2 hits · run 2026-09-09
1 retrieved record(s)
does_not_resolve 20372089 · Human vaccines (2010) — Safety and immunogenicity of a live attenuated varicella vaccine in VZV-seropositive HIV-infected adults.
E3 · Infection contrastno_data
Measure: Mediator absent/low after natural infection Comparator: Recovered natural infection Hit rule: Mediator signal is specific to vaccination vs a comparable natural-infection control
Finding: No retrieved evidence directly addresses whether a mediator signal specific to vaccination vs a comparable natural-infection control is absent or low after natural infection for Herpes zoster attributed to Shingles vaccine.
Cited: (none)
supporting: Shingles (zoster) vaccine Herpes zoster mechanism Infection contrast in vitro OR patient-derived pubmed · 29264 hits · run 2026-09-09
mirror: Shingles (zoster) vaccine Herpes zoster Infection contrast not associated mechanism pubmed · 56 hits · run 2026-09-09
9 retrieved record(s)
does_not_resolve 32963118 · Current issues in molecular biology (2021) — Alphaherpesvirus Vaccines.
does_not_resolve 20550454 · Clinical infectious diseases : an offici (2010) — Zoster vaccine: current status and future prospects.
does_not_resolve 41100077 · Rheumatology (Oxford, England) (2026) — Differences in immunogenicity to zoster recombinant vaccine in IMID patients undergoing treatment with non-selective or selective JAK-i.
does_not_resolve 19553630 · The Journal of the American Osteopathic (2009) — Herpes zoster pathogenesis and cell-mediated immunity and immunosenescence.
does_not_resolve 42228420 · JCI insight (2026) — Age-related differences in immune responses to inactivated influenza and adjuvanted recombinant herpes zoster vaccines.
does_not_resolve 40331755 · Human vaccines & immunotherapeutics (2025) — Varicella zoster virus mRNA vaccine candidate induced superior cellular immunity and comparable humoral and Fc-mediated immunity compared to the licensed subuni
does_not_resolve 31369608 · PloS one (2019) — Determinants of shingles vaccine acceptance in the United Kingdom.
does_not_resolve 31543415 · Vaccine (2019) — VZV-specific cell-mediated immunity, but not humoral immunity, correlates inversely with the incidence of herpes zoster and the severity of skin symptoms and zo
E4 · Transfer to recipientno_data
Measure: Phenotype/mediator transferred to a recipient system Comparator: Control transfer Hit rule: The effect / mediator transfers to a naive recipient system
Finding: no evidence found
Cited: (none)
supporting: Shingles (zoster) vaccine Herpes zoster mechanism Transfer to recipient in vitro OR patient-derived pubmed · 29262 hits · run 2026-09-09
mirror: Shingles (zoster) vaccine Herpes zoster Transfer to recipient not associated mechanism pubmed · 1 hits · run 2026-09-09
E5 · Transfer specificityno_data
Measure: Transfer requires the specific mediator Comparator: Transfer with mediator present Hit rule: Transfer effect is lost when the specific mediator is removed
Finding: The retrieved evidence describes attempts to produce herpes zoster lesions in animals by injecting vesicle material from human cases, but it does not address transfer specificity for Shingles (zoster) vaccine causing herpes zoster, nor does it involve removal of a specific mediator.
supporting: Shingles (zoster) vaccine Herpes zoster mechanism Transfer specificity in vitro OR patient-derived pubmed · 29262 hits · run 2026-09-09
mirror: Shingles (zoster) vaccine Herpes zoster Transfer specificity not associated mechanism pubmed · 5 hits · run 2026-09-09
1 retrieved record(s)
does_not_resolve 19869091 · The Journal of experimental medicine (1925) — THE PROBLEM OF THE ETIOLOGY OF HERPES ZOSTER.
E6 · Depletion / knockdownno_data
Measure: Removing the mediator reduces the effect Comparator: Non-targeted knockdown Hit rule: Knockdown / depletion of the mediator reduces the phenotype
Finding: no evidence found
Cited: (none)
supporting: Shingles (zoster) vaccine Herpes zoster mechanism Depletion / knockdown in vitro OR patient-derived pubmed · 29262 hits · run 2026-09-09
Measure: Adding the mediator restores the effect Comparator: Add-back of a control protein Hit rule: Adding back the mediator (not a control) restores the phenotype
Finding: no evidence found
Cited: (none)
supporting: Shingles (zoster) vaccine Herpes zoster mechanism Add-back rescue in vitro OR patient-derived pubmed · 29262 hits · run 2026-09-09
Measure: Neutralizing the mediator blocks the effect Comparator: Isotype control Hit rule: Neutralization of the mediator (not an isotype control) blocks the phenotype
Finding: No retrieved evidence directly addresses whether neutralization of a specific mediator blocks the phenotype of new herpes zoster attributed to shingles vaccine. Several studies measure neutralizing antibody responses to varicella-zoster virus after vaccination, but none test blocking the clinical phenotype via neutralization of a mediator.
Cited: (none)
supporting: Shingles (zoster) vaccine Herpes zoster mechanism Neutralization in vitro OR patient-derived pubmed · 29262 hits · run 2026-09-09
mirror: Shingles (zoster) vaccine Herpes zoster Neutralization not associated mechanism pubmed · 59 hits · run 2026-09-09
8 retrieved record(s)
does_not_resolve 40813770 · NPJ vaccines (2025) — A self-amplifying mRNA vaccine expressing PRV gD induces robust immunity against virulent mutants.
does_not_resolve 41418604 · Vaccine (2026) — Herpes zoster mRNA vaccine elicits superior immune responses over licensed vaccines with a favorable safety profile in animal models.
does_not_resolve 38006010 · Vaccines (2023) — Pre-Clinical Development of an Adenovirus Vector Based RSV and Shingles Vaccine Candidate.
does_not_resolve 42079457 · Clinical kidney journal (2026) — Vaccine efficacy in CKD patients not on dialysis: a systematic review and meta-analysis.
does_not_resolve 38423817 · Vaccine (2024) — Effect of high dose vitamin D supplementation on subsequent immune responses to administration of the live herpes zoster vaccine to long-term care residents.
does_not_resolve 41575203 · Human vaccines & immunotherapeutics (2026) — BC02-adjuvanted varicella-zoster virus glycoprotein E subunit vaccine overcomes immunosenescence to induce robust neutralizing antibodies and multifunctional T-
does_not_resolve 33762414 · Journal of virology (2021) — Comparative Antibody Responses to the Live-Attenuated and Recombinant Herpes Zoster Vaccines.
does_not_resolve 35746685 · Viruses (2022) — Immunogenicity of Varicella Zoster Virus DNA Vaccines Encoding Glycoprotein E and Immediate Early Protein 63 in Mice.
E9 · Isotype controlno_data
Measure: Isotype control does not reproduce the effect Comparator: Active antibody Hit rule: An isotype control fails to reproduce the block/activation
Finding: No retrieved evidence describes the use of an isotype control in the context of the Shingles vaccine and herpes zoster, nor whether an isotype control fails to reproduce a block or activation related to that outcome.
Cited: (none)
supporting: Shingles (zoster) vaccine Herpes zoster mechanism Isotype control in vitro OR patient-derived pubmed · 29262 hits · run 2026-09-09
mirror: Shingles (zoster) vaccine Herpes zoster Isotype control not associated mechanism pubmed · 48 hits · run 2026-09-09
9 retrieved record(s)
does_not_resolve 34570596 · Annals of internal medicine (2021) — The Safety and Immunologic Effectiveness of the Live Varicella-Zoster Vaccine in Patients Receiving Tumor Necrosis Factor Inhibitor Therapy : A Randomized Contr
does_not_resolve 40916263 · Vaccine (2025) — Safety, immunogenicity and efficacy of the Shingrix vaccine in immunocompromised varicella zoster virus naïve pediatric patients.
does_not_resolve 41529719 · Human vaccines & immunotherapeutics (2026) — TLR9 and STING agonists adjuvanted varicella-zoster virus glycoprotein E induced a potent and durable nasal vaccine response.
does_not_resolve 40479925 · Vaccine (2025) — Long-term immunogenicity of a live attenuated herpes zoster vaccine in patients with systemic lupus erythematosus.
refutes_node 27057679 · Inflammatory bowel diseases (2016) — Herpes Zoster Vaccine Response in Inflammatory Bowel Disease Patients on Low-dose Immunosuppression.
does_not_resolve 41635931 · Expert review of vaccines (2026) — Fc-mediated immune effector functions elicited by recombinant and live-attenuated herpes zoster vaccines.
does_not_resolve 42084498 · Human vaccines & immunotherapeutics (2026) — Effect of nipocalimab on IgG responses to vaccinations and viral infections in patients with IgG autoantibody-mediated diseases: Post hoc analyses of three rand
does_not_resolve 41124868 · Biomedicine & pharmacotherapy = Biomedec (2025) — Sex and age-related differences in humoral and cellular responses to the recombinant zoster vaccine in people living with HIV.
F1 · Full product reproducesno_data
Measure: Full vaccine product reproduces the effect Comparator: No-product control Hit rule: The full product (not a subcomponent) reproduces the effect
Finding: No retrieved evidence addresses Shingles (zoster) vaccine causing new Herpes zoster; all retrieved abstracts discuss unrelated vaccine vectors (measles, Newcastle disease, malaria, rabies, avian paramyxoviruses, DNA, bacterial, capripoxviruses) or platform technologies, with no mention of zoster vaccine or herpes zoster.
Cited: (none)
supporting: Shingles (zoster) vaccine Herpes zoster Full product reproduces component OR antigen OR vector pubmed · 2045628 hits · run 2026-09-09
mirror: Shingles (zoster) vaccine Herpes zoster Full product reproduces no effect component isolation pubmed · 0 hits (0 hits — negative) · run 2026-09-09
does_not_resolve 15174971 · Expert opinion on biological therapy (2004) — Particle-mediated DNA vaccine delivery to the skin.
does_not_resolve 29550258 · Immunology letters (2018) — Live bacterial vaccine vector and delivery strategies of heterologous antigen: A review.
F2 · Empty vector / particleno_data
Measure: Vector/particle without antigen reproduces (or not) Comparator: Full product Hit rule: Effect attributed to (or excluded from) the vector/particle backbone alone
Finding: Retrieved evidence includes general discussions of viral vector vaccine platforms (e.g., lentiviral, NDV, capripoxvirus, APMV) but no mention of Shingles (zoster) vaccine or its vector/particle backbone. No evidence links an empty vector/particle to reproduction of Herpes zoster or to vaccine-attributed adverse events.
Cited: (none)
supporting: Shingles (zoster) vaccine Herpes zoster Empty vector / particle component OR antigen OR vector pubmed · 2045628 hits · run 2026-09-09
does_not_resolve 25142448 · Current gene therapy (2014) — Improving DNA vaccine performance through vector design.
does_not_resolve 29550258 · Immunology letters (2018) — Live bacterial vaccine vector and delivery strategies of heterologous antigen: A review.
does_not_resolve 31300111 · Comparative immunology, microbiology and (2019) — Construction of recombinant capripoxviruses as vaccine vectors for delivering foreign antigens: Methodology and application.
F4 · Irrelevant cargono_data
Measure: Irrelevant cargo does not reproduce the effect Comparator: Vector with the target antigen Hit rule: Irrelevant cargo fails to reproduce the effect (specificity)
Finding: The retrieved evidence does not address the specific node of whether an irrelevant cargo (e.g., a non-zoster vaccine component) fails to reproduce herpes zoster after shingles vaccination. The papers discuss vaccine vector technologies for other pathogens (measles, rabies, malaria, etc.), not the specificity of adverse events for the shingles vaccine.
Cited: (none)
supporting: Shingles (zoster) vaccine Herpes zoster Irrelevant cargo component OR antigen OR vector pubmed · 2045628 hits · run 2026-09-09
does_not_resolve 25142448 · Current gene therapy (2014) — Improving DNA vaccine performance through vector design.
does_not_resolve 29550258 · Immunology letters (2018) — Live bacterial vaccine vector and delivery strategies of heterologous antigen: A review.
does_not_resolve 31300111 · Comparative immunology, microbiology and (2019) — Construction of recombinant capripoxviruses as vaccine vectors for delivering foreign antigens: Methodology and application.
F5 · Infection preparationno_data
Measure: Infection preparation vs product comparison Comparator: Product-derived preparation Hit rule: Effect compares correctly between infection and product preparations
Finding: no evidence found
Cited: (none)
supporting: Shingles (zoster) vaccine Herpes zoster Infection preparation component OR antigen OR vector pubmed · 2045630 hits · run 2026-09-09
does_not_resolve 25142448 · Current gene therapy (2014) — Improving DNA vaccine performance through vector design.
does_not_resolve 29550258 · Immunology letters (2018) — Live bacterial vaccine vector and delivery strategies of heterologous antigen: A review.
does_not_resolve 31300111 · Comparative immunology, microbiology and (2019) — Construction of recombinant capripoxviruses as vaccine vectors for delivering foreign antigens: Methodology and application.
F6 · Cytokine / adjuvant mixno_data
Measure: Cytokine/adjuvant mix alone reproduces (or not) Comparator: Individual components Hit rule: The effect is (or is not) reproducible by the cytokine/adjuvant mix alone
Finding: no evidence found
Cited: (none)
supporting: Shingles (zoster) vaccine Herpes zoster Cytokine / adjuvant mix component OR antigen OR vector pubmed · 2045628 hits · run 2026-09-09
does_not_resolve 15174971 · Expert opinion on biological therapy (2004) — Particle-mediated DNA vaccine delivery to the skin.
does_not_resolve 29550258 · Immunology letters (2018) — Live bacterial vaccine vector and delivery strategies of heterologous antigen: A review.
F7 · Component combinationno_data
Measure: Defined component combination reproduces the effect Comparator: Single components Hit rule: A defined combination reproduces the effect that single components do not
Finding: No retrieved evidence describes a defined component combination of the shingles (zoster) vaccine that reproduces herpes zoster when single components do not.
Cited: (none)
supporting: Shingles (zoster) vaccine Herpes zoster Component combination component OR antigen OR vector pubmed · 2045633 hits · run 2026-09-09
Measure: Effect reproduced in 2D human cell culture Comparator: Untreated / control cells Hit rule: Effect reproduced in 2D primary human cells
Finding: no evidence found
Cited: (none)
supporting: Shingles (zoster) vaccine Herpes zoster 2D human cells animal OR organoid OR cell model pubmed · 1819226 hits · run 2026-09-09
mirror: Shingles (zoster) vaccine Herpes zoster 2D human cells not reproduced model pubmed · 0 hits (0 hits — negative) · run 2026-09-09
G2 · Organoid / chipno_data
Measure: Effect reproduced in organoid / organ-on-chip Comparator: Unexposed organoid Hit rule: Effect reproduced in a 3D organoid / organ-on-chip system
Finding: no evidence found
Cited: (none)
supporting: Shingles (zoster) vaccine Herpes zoster Organoid / chip animal OR organoid OR cell model pubmed · 1819226 hits · run 2026-09-09
mirror: Shingles (zoster) vaccine Herpes zoster Organoid / chip not reproduced model pubmed · 0 hits (0 hits — negative) · run 2026-09-09
H1 · Block in vitro / in vivono_data
Measure: Blocking the mediator/mechanism prevents the effect Comparator: Control intervention Hit rule: Blocking the mechanism prevents or reverses the effect (not with a control intervention)
Finding: no evidence found
Cited: (none)
supporting: Shingles (zoster) vaccine Herpes zoster Block in vitro / in vivo intervention OR treatment OR reversal pubmed · 15145596 hits · run 2026-09-09
mirror: Shingles (zoster) vaccine Herpes zoster Block in vitro / in vivo no effect intervention pubmed · 0 hits (0 hits — negative) · run 2026-09-09
Clinical / animal / host 7/7 evaluated
E10 · Host-line dependenceno_data
Measure: Effect depends on host line/cell type Comparator: Susceptible host line Hit rule: Effect is restricted to a defined host line / genotype, not universal
Finding: no evidence found
Cited: (none)
supporting: Shingles (zoster) vaccine Herpes zoster mechanism Host-line dependence in vitro OR patient-derived pubmed · 29262 hits · run 2026-09-09
Measure: Effect in animal via the clinical route of administration Comparator: Vehicle, same route Hit rule: Effect reproduced in an animal using the clinical route of administration
Finding: The retrieved evidence describes non-clinical safety assessment of the gE/AS01 zoster vaccine in rabbits, focusing on local inflammatory reactions after single intramuscular or subcutaneous administration; it does not report reproduction of Herpes zoster (shingles) in animals via the clinical route of administration.
supporting: Shingles (zoster) vaccine Herpes zoster Animal, clinical route animal OR organoid OR cell model pubmed · 1819228 hits · run 2026-09-09
mirror: Shingles (zoster) vaccine Herpes zoster Animal, clinical route not reproduced model pubmed · 2 hits · run 2026-09-09
1 retrieved record(s)
does_not_resolve 27172098 · Journal of applied toxicology : JAT (2017) — Non-clinical safety assessment of single and repeated administration of gE/AS01 zoster vaccine in rabbits.
G4 · Susceptible animalno_data
Measure: Effect in a susceptible animal model Comparator: Non-susceptible model Hit rule: Effect in a defined susceptible animal model
Finding: No evidence found that addresses an effect of the Shingles (zoster) vaccine in a defined susceptible animal model; PMID 39280450 discusses human vaccine utilization, PMID 19869091 describes historical animal injection with herpes zoster material (not vaccine), and PMID 15661165 evaluates varicella vaccine strains in a mouse model but not the Shingles vaccine.
Cited: (none)
supporting: Shingles (zoster) vaccine Herpes zoster Susceptible animal animal OR organoid OR cell model pubmed · 1819233 hits · run 2026-09-09
mirror: Shingles (zoster) vaccine Herpes zoster Susceptible animal not reproduced model pubmed · 9 hits · run 2026-09-09
3 retrieved record(s)
does_not_resolve 39280450 · Cureus (2024) — Factors Influencing Herpes Zoster Vaccine Utilization Among Adults Aged 50 and Above Attending Primary Healthcare Center in Saudi Arabia: A Cross-Sectional Stud
does_not_resolve 19869091 · The Journal of experimental medicine (1925) — THE PROBLEM OF THE ETIOLOGY OF HERPES ZOSTER.
does_not_resolve 15661165 · Virology (2005) — Analysis of varicella zoster virus attenuation by evaluation of chimeric parent Oka/vaccine Oka recombinant viruses in skin xenografts in the SCIDhu mouse model
G5 · Replication across labsno_data
Measure: Effect replicated in an independent lab Comparator: Original result Hit rule: The key effect is replicated in an independent laboratory
Finding: no evidence found
Cited: (none)
supporting: Shingles (zoster) vaccine Herpes zoster Replication across labs animal OR organoid OR cell model pubmed · 1819226 hits · run 2026-09-09
mirror: Shingles (zoster) vaccine Herpes zoster Replication across labs not reproduced model pubmed · 0 hits (0 hits — negative) · run 2026-09-09
G6 · Blinded scoringno_data
Measure: Outcomes scored blinded Comparator: Unblinded reference Hit rule: Primary outcomes scored by a blinded assessor
Finding: The retrieved evidence describes randomized, double-blind, placebo-controlled trials for the shingles vaccine (RZV or live attenuated), but none report a primary outcome of new Herpes zoster cases scored by a blinded assessor. The trials focus on immunogenicity, safety, or quality-of-life measures, not on blinded adjudication of incident Herpes zoster as a primary endpoint.
Cited: (none)
supporting: Shingles (zoster) vaccine Herpes zoster Blinded scoring animal OR organoid OR cell model pubmed · 1819226 hits · run 2026-09-09
mirror: Shingles (zoster) vaccine Herpes zoster Blinded scoring not reproduced model pubmed · 5 hits · run 2026-09-09
5 retrieved record(s)
ambiguous 40036115 · Journal of clinical rheumatology : pract (2025) — Disease Safety, Immunogenicity, and Efficacy of Recombinant Herpes Zoster Vaccine (RZV or Shingrix) in Autoimmune Rheumatic Diseases: Launching a Randomized Pha
does_not_resolve 41672807 · Annals of the rheumatic diseases (2026) — Safety and immunogenicity of the recombinant zoster vaccine in patients with rheumatoid arthritis using abatacept: a pilot multicentre, double-blind, randomised
refutes_node 26605507 · Diabetic medicine : a journal of the Bri (2016) — Efficacy and safety of live varicella zoster vaccine in diabetes: a randomized, double-blind, placebo-controlled trial.
supports_node 20863322 · Journal of the American Geriatrics Socie (2010) — Effect of a zoster vaccine on herpes zoster-related interference with functional status and health-related quality-of-life measures in older adults.
does_not_resolve 42294825 · Arthritis care & research (2026) — Immunogenicity, Safety, and Determinants of Recombinant Zoster Vaccine Response in Idiopathic Inflammatory Myopathies: A Phase 4 Randomized Trial.
G7 · Experimental time courseno_data
Measure: Effect follows a defined experimental time course Comparator: No-exposure time course Hit rule: The effect's onset/offset follows a defined experimental time course
Finding: no evidence found
Cited: (none)
supporting: Shingles (zoster) vaccine Herpes zoster Experimental time course animal OR organoid OR cell model pubmed · 1819226 hits · run 2026-09-09
mirror: Shingles (zoster) vaccine Herpes zoster Experimental time course not reproduced model pubmed · 2 hits · run 2026-09-09
I4 · Susceptibility traitno_data
Measure: A host trait / marker defines susceptibility Comparator: Trait-negative hosts Hit rule: A defined host trait / marker enriches for susceptibility
Finding: no evidence found
Cited: (none)
supporting: Shingles (zoster) vaccine Herpes zoster Susceptibility trait coherence OR latency OR susceptibility pubmed · 870319 hits · run 2026-09-09
mirror: Shingles (zoster) vaccine Herpes zoster Susceptibility trait inconsistent OR contradicts pubmed · 27616 hits · run 2026-09-09
1 retrieved record(s)
does_not_resolve 25187623 · Reproduction (Cambridge, England) (2014) — Epigenetics and life-long consequences of an adverse nutritional and diabetic intrauterine environment.
How this was built
Per node: a supporting and a mirror PubMed query built from the node's measure / population / comparator / hit_rule; top hits fetched (title + abstract); each record classified (supports / refutes / ambiguous) by xAI with a heuristic fallback; a per-node synthesis is generated strictly from the retrieved PMIDs; the node status is then rolled up to C1–C6. Full query provenance is shown per node above. Reproduce the build: python -m evidence_run. Data: data/evidence_run/state.json.