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Shingles (zoster) vaccine → Post herpetic neuralgia

Evidence dossier · candidate cand-shingles-post-herpetic-neuralgia · VICP program · · DRAFT — not a determination
This is a draft research-tracking dossier, not a determination that Shingles (zoster) vaccine causes Post herpetic neuralgia, 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)

ClaimLabelStatusMissing nodes
C1Coherent clinical object existsinsufficient_datamissing: A2
C2Consistent temporal windowsupported
C3Epidemiologic excess riskcontested
C4Consistency / replicationcontested
C5Specificity (product / dose)contested
C6Biological mechanisminsufficient_datamissing: E1

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.

ViewpointWhat it asksStatus (from evidence)
Temporality (necessary)cause precedes effect in a plausible window (necessary)not established
Strengthsize/precision of the associationnot established
Consistencyreproduced across settings/designsnot established
Specificitytied to a specific product/dose/outcomenot established
Biological gradientdose-responsenot established
Plausibilitya named biological mechanismnot established
Coherencefits known biology/natural historynot established
Experimentintervention changes risknot established
Analogyprecedent for the patternnot established

NASEM weight-of-evidence synthesis (computed)

TrackWeightBasis
EpidemiologicINSUFFICIENTvia B1, B2, B3, B4, B5, B8
MechanisticLACKINGvia A9, A10, C1n, C2n, C3n, C4n, C5n · missing: D1 D2 D3 D4 D5 E1 E2 E3 E4 E5 E6 E7 E8 E9 E10 F1 …
Synthesized conclusionInadequate to accept or reject

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 reportsno_data
Measure: New definite object in risk window T
Comparator: Pre-vaccination baseline
Hit rule: Definite object present, onset in window, competing causes considered
Finding: The retrieved evidence includes only case reports of herpes zoster reactivation and post-herpetic neuralgia following COVID-19 vaccines, not shingles (zoster) vaccine. One case report (PMID 36874700) describes herpes zoster reactivation after Shingrix vaccine but does not report post-herpetic neuralgia.
Case-certainty distribution (no established case definition): 1 Probable, 2 Possible/unclassifiable. Transparency layer — does not change this node's status or feed C1–C6.
Cited: PMID 36874700
supporting: Shingles (zoster) vaccine Post herpetic neuralgia case report OR case series Case reports
pubmed · 66210 hits · run 2026-09-09
mirror: Shingles (zoster) vaccine Post herpetic neuralgia alternative diagnosis OR not vaccine-related
pubmed · 4057 hits · run 2026-09-09
16 retrieved record(s)
ambiguous 37052164 · Agri : Agri (Algoloji) Dernegi'nin Yayin (2023) — Inactivated COVID-19 vaccine-related herpes zoster and post-herpetic neuralgia: Three case reports.
supports_node 38721437 · Anesthesiology and pain medicine (2023) — Herpes Zoster Reactivation After COVID-19 Vaccine with Focus on Postherpetic Neuralgia Prevention: A Case Series.
supports_node 36874700 · Cureus (2023) — Reactivation of Herpes Zoster After Recombinant Vaccine (Shingrix): A Case Report.
does_not_resolve 36752132 · Revista espanola de quimioterapia : publ (2023) — Status of Herpes Zoster and Herpes Zoster Vaccines in 2023: A position paper.
ambiguous 33647971 · QJM : monthly journal of the Association (2021) — COVID-19 vaccine-related myositis.
ambiguous 34854882 · Blood (2021) — VITT(al) insights into vaccine-related clots.
does_not_resolve 37775180 · Clinical medicine (London, England) (2023) — SARS-CoV-2 vaccines and myocarditis.
does_not_resolve 30000765 · (2006) — Human Papillomavirus Vaccines.
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 evidence found
Case-certainty distribution (no established case definition): 1 Possible/unclassifiable. Transparency layer — does not change this node's status or feed C1–C6.
Cited: (none)
supporting: Shingles (zoster) vaccine Post herpetic neuralgia case report OR case series Series with objective confirmation
pubmed · 5668 hits · run 2026-09-09
mirror: Shingles (zoster) vaccine Post herpetic neuralgia alternative diagnosis OR not vaccine-related
pubmed · 4057 hits · run 2026-09-09
12 retrieved record(s)
ambiguous 33647971 · QJM : monthly journal of the Association (2021) — COVID-19 vaccine-related myositis.
ambiguous 34854882 · Blood (2021) — VITT(al) insights into vaccine-related clots.
does_not_resolve 37775180 · Clinical medicine (London, England) (2023) — SARS-CoV-2 vaccines and myocarditis.
ambiguous 30000765 · (2006) — Human Papillomavirus Vaccines.
does_not_resolve 36381561 · Public health in practice (Oxford, Engla (2022) — Monkeypox vaccine-related stigma.
does_not_resolve 16871116 · Pediatric emergency care (2006) — Vaccination-related adverse events.
does_not_resolve 36441403 · Current cardiology reports (2022) — COVID-19 Vaccine-Related Myocardial and Pericardial Inflammation.
ambiguous 7114977 · Archives of internal medicine (1982) — Vaccine-related poliomyelitis.
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 includes three case reports and one case series describing post-herpetic neuralgia (PHN) following COVID-19 vaccination (not specifically shingles vaccine), and two case reports of herpes zoster after Shingrix (recombinant zoster vaccine) but without mention of PHN as an outcome in those specific cases. No evidence retrieved directly addresses the onset distribution of PHN attributed to shingles (zoster) vaccine.
Cited: (none)
supporting: Shingles (zoster) vaccine Post herpetic neuralgia case report OR case series Onset histogram
pubmed · 26 hits · run 2026-09-09
mirror: Shingles (zoster) vaccine Post herpetic neuralgia alternative diagnosis OR not vaccine-related
pubmed · 4057 hits · run 2026-09-09
18 retrieved record(s)
supports_node 37052164 · Agri : Agri (Algoloji) Dernegi'nin Yayin (2023) — Inactivated COVID-19 vaccine-related herpes zoster and post-herpetic neuralgia: Three case reports.
supports_node 36874700 · Cureus (2023) — Reactivation of Herpes Zoster After Recombinant Vaccine (Shingrix): A Case Report.
does_not_resolve 36752132 · Revista espanola de quimioterapia : publ (2023) — Status of Herpes Zoster and Herpes Zoster Vaccines in 2023: A position paper.
supports_node 38721437 · Anesthesiology and pain medicine (2023) — Herpes Zoster Reactivation After COVID-19 Vaccine with Focus on Postherpetic Neuralgia Prevention: A Case Series.
supports_node 41769456 · Cureus (2026) — Herpes Zoster Induced by the Shingrix Vaccine: A Case Report and Literature Review.
supports_node 37228567 · Cureus (2023) — Can the COVID-19 Vaccine Cause Recrudescence of Herpes Zoster Virus While Taking Antiviral Medication?
does_not_resolve 33647971 · QJM : monthly journal of the Association (2021) — COVID-19 vaccine-related myositis.
ambiguous 34854882 · Blood (2021) — VITT(al) insights into vaccine-related clots.
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 case reports of herpes zoster (shingles) reactivation after COVID-19 or Shingrix vaccination, some with post-herpetic neuralgia; however, none of the cited papers address post-herpetic neuralgia attributed specifically to a shingles (zoster) vaccine with onset latency consistent with the object's pathophysiology, and no evidence is provided for temporal plausibility of post-herpetic neuralgia following shingles vaccine.
Cited: (none)
supporting: Shingles (zoster) vaccine Post herpetic neuralgia case report OR case series Temporal plausibility
pubmed · 55 hits · run 2026-09-09
mirror: Shingles (zoster) vaccine Post herpetic neuralgia alternative diagnosis OR not vaccine-related
pubmed · 4057 hits · run 2026-09-09
17 retrieved record(s)
supports_node 37052164 · Agri : Agri (Algoloji) Dernegi'nin Yayin (2023) — Inactivated COVID-19 vaccine-related herpes zoster and post-herpetic neuralgia: Three case reports.
supports_node 36874700 · Cureus (2023) — Reactivation of Herpes Zoster After Recombinant Vaccine (Shingrix): A Case Report.
does_not_resolve 36752132 · Revista espanola de quimioterapia : publ (2023) — Status of Herpes Zoster and Herpes Zoster Vaccines in 2023: A position paper.
supports_node 38721437 · Anesthesiology and pain medicine (2023) — Herpes Zoster Reactivation After COVID-19 Vaccine with Focus on Postherpetic Neuralgia Prevention: A Case Series.
supports_node 41769456 · Cureus (2026) — Herpes Zoster Induced by the Shingrix Vaccine: A Case Report and Literature Review.
does_not_resolve 33647971 · QJM : monthly journal of the Association (2021) — COVID-19 vaccine-related myositis.
ambiguous 34854882 · Blood (2021) — VITT(al) insights into vaccine-related clots.
does_not_resolve 37775180 · Clinical medicine (London, England) (2023) — SARS-CoV-2 vaccines and myocarditis.
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: None of the retrieved case reports or review articles specifically document a recorded onset interval for post-herpetic neuralgia attributed to shingles (zoster) vaccine in a primary source; the reports describe herpes zoster after COVID-19 or shingles vaccine but do not provide explicit documentation of onset interval for PHN as a separate adverse event.
Cited: (none)
supporting: Shingles (zoster) vaccine Post herpetic neuralgia case report OR case series Onset-interval documentation
pubmed · 24 hits · run 2026-09-09
mirror: Shingles (zoster) vaccine Post herpetic neuralgia alternative diagnosis OR not vaccine-related
pubmed · 4057 hits · run 2026-09-09
18 retrieved record(s)
ambiguous 37052164 · Agri : Agri (Algoloji) Dernegi'nin Yayin (2023) — Inactivated COVID-19 vaccine-related herpes zoster and post-herpetic neuralgia: Three case reports.
supports_node 36874700 · Cureus (2023) — Reactivation of Herpes Zoster After Recombinant Vaccine (Shingrix): A Case Report.
does_not_resolve 36752132 · Revista espanola de quimioterapia : publ (2023) — Status of Herpes Zoster and Herpes Zoster Vaccines in 2023: A position paper.
ambiguous 38721437 · Anesthesiology and pain medicine (2023) — Herpes Zoster Reactivation After COVID-19 Vaccine with Focus on Postherpetic Neuralgia Prevention: A Case Series.
supports_node 41769456 · Cureus (2026) — Herpes Zoster Induced by the Shingrix Vaccine: A Case Report and Literature Review.
supports_node 37228567 · Cureus (2023) — Can the COVID-19 Vaccine Cause Recrudescence of Herpes Zoster Virus While Taking Antiviral Medication?
ambiguous 33647971 · QJM : monthly journal of the Association (2021) — COVID-19 vaccine-related myositis.
ambiguous 34854882 · Blood (2021) — VITT(al) insights into vaccine-related clots.
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 evidence found
Case-certainty distribution (no established case definition): 1 Possible/unclassifiable. Transparency layer — does not change this node's status or feed C1–C6.
Cited: (none)
supporting: Shingles (zoster) vaccine Post herpetic neuralgia case report OR case series Differential diagnosis excluded
pubmed · 451 hits · run 2026-09-09
mirror: Shingles (zoster) vaccine Post herpetic neuralgia alternative diagnosis OR not vaccine-related
pubmed · 4057 hits · run 2026-09-09
12 retrieved record(s)
ambiguous 33647971 · QJM : monthly journal of the Association (2021) — COVID-19 vaccine-related myositis.
ambiguous 34854882 · Blood (2021) — VITT(al) insights into vaccine-related clots.
does_not_resolve 37775180 · Clinical medicine (London, England) (2023) — SARS-CoV-2 vaccines and myocarditis.
does_not_resolve 30000765 · (2006) — Human Papillomavirus Vaccines.
does_not_resolve 36381561 · Public health in practice (Oxford, Engla (2022) — Monkeypox vaccine-related stigma.
does_not_resolve 16871116 · Pediatric emergency care (2006) — Vaccination-related adverse events.
does_not_resolve 36441403 · Current cardiology reports (2022) — COVID-19 Vaccine-Related Myocardial and Pericardial Inflammation.
ambiguous 7114977 · Archives of internal medicine (1982) — Vaccine-related poliomyelitis.
A7 · Rechallenge / re-exposureno_data
Measure: Object recurs on a further dose
Comparator: First-dose response
Hit rule: Object recurs after a subsequent dose (re-exposure)
Finding: The retrieved evidence includes only case reports of herpes zoster (HZ) reactivation after COVID-19 vaccination and one case of HZ after Shingrix vaccine; none report a recurrence of post-herpetic neuralgia (PHN) after a subsequent dose of Shingles (zoster) vaccine (rechallenge/re-exposure).
Cited: (none)
supporting: Shingles (zoster) vaccine Post herpetic neuralgia case report OR case series Rechallenge / re-exposure
pubmed · 26 hits · run 2026-09-09
mirror: Shingles (zoster) vaccine Post herpetic neuralgia alternative diagnosis OR not vaccine-related
pubmed · 4057 hits · run 2026-09-09
17 retrieved record(s)
supports_node 37052164 · Agri : Agri (Algoloji) Dernegi'nin Yayin (2023) — Inactivated COVID-19 vaccine-related herpes zoster and post-herpetic neuralgia: Three case reports.
supports_node 36874700 · Cureus (2023) — Reactivation of Herpes Zoster After Recombinant Vaccine (Shingrix): A Case Report.
does_not_resolve 36752132 · Revista espanola de quimioterapia : publ (2023) — Status of Herpes Zoster and Herpes Zoster Vaccines in 2023: A position paper.
ambiguous 38721437 · Anesthesiology and pain medicine (2023) — Herpes Zoster Reactivation After COVID-19 Vaccine with Focus on Postherpetic Neuralgia Prevention: A Case Series.
supports_node 41769456 · Cureus (2026) — Herpes Zoster Induced by the Shingrix Vaccine: A Case Report and Literature Review.
does_not_resolve 33647971 · QJM : monthly journal of the Association (2021) — COVID-19 vaccine-related myositis.
ambiguous 34854882 · Blood (2021) — VITT(al) insights into vaccine-related clots.
does_not_resolve 37775180 · Clinical medicine (London, England) (2023) — SARS-CoV-2 vaccines and myocarditis.
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 three case reports (PMIDs 37052164, 38721437, 36874700) describing post-herpetic neuralgia following COVID-19 or recombinant zoster vaccine, but none adjudicate cases as 'definite' by a published criterion set for the pair Shingles vaccine -> Post herpetic neuralgia, and one case (PMID 41769456) reports shingles after Shingrix without mention of post-herpetic neuralgia.
Case-certainty distribution (no established case definition): 4 Probable. Transparency layer — does not change this node's status or feed C1–C6.
Cited: (none)
supporting: Shingles (zoster) vaccine Post herpetic neuralgia case report OR case series Adjudicated by criteria
pubmed · 63 hits · run 2026-09-09
mirror: Shingles (zoster) vaccine Post herpetic neuralgia alternative diagnosis OR not vaccine-related
pubmed · 4057 hits · run 2026-09-09
17 retrieved record(s)
supports_node 37052164 · Agri : Agri (Algoloji) Dernegi'nin Yayin (2023) — Inactivated COVID-19 vaccine-related herpes zoster and post-herpetic neuralgia: Three case reports.
does_not_resolve 36752132 · Revista espanola de quimioterapia : publ (2023) — Status of Herpes Zoster and Herpes Zoster Vaccines in 2023: A position paper.
supports_node 36874700 · Cureus (2023) — Reactivation of Herpes Zoster After Recombinant Vaccine (Shingrix): A Case Report.
supports_node 41769456 · Cureus (2026) — Herpes Zoster Induced by the Shingrix Vaccine: A Case Report and Literature Review.
ambiguous 38721437 · Anesthesiology and pain medicine (2023) — Herpes Zoster Reactivation After COVID-19 Vaccine with Focus on Postherpetic Neuralgia Prevention: A Case Series.
ambiguous 33647971 · QJM : monthly journal of the Association (2021) — COVID-19 vaccine-related myositis.
does_not_resolve 34854882 · Blood (2021) — VITT(al) insights into vaccine-related clots.
does_not_resolve 37775180 · Clinical medicine (London, England) (2023) — SARS-CoV-2 vaccines and myocarditis.
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 does not describe post-herpetic neuralgia following a shingles (zoster) vaccine. One case report (PMID 37052164) describes PHN after an inactivated COVID-19 vaccine, and another (PMID 36874700) reports herpes zoster reactivation after Shingrix, but without PHN. A position paper (PMID 36752132) discusses HZ and vaccines generally but provides no specific case data for PHN after a zoster vaccine.
Cited: (none)
supporting: Shingles (zoster) vaccine Post herpetic neuralgia case report OR case series Natural-history consistency
pubmed · 127 hits · run 2026-09-09
mirror: Shingles (zoster) vaccine Post herpetic neuralgia alternative diagnosis OR not vaccine-related
pubmed · 4057 hits · run 2026-09-09
15 retrieved record(s)
does_not_resolve 37052164 · Agri : Agri (Algoloji) Dernegi'nin Yayin (2023) — Inactivated COVID-19 vaccine-related herpes zoster and post-herpetic neuralgia: Three case reports.
supports_node 36874700 · Cureus (2023) — Reactivation of Herpes Zoster After Recombinant Vaccine (Shingrix): A Case Report.
does_not_resolve 36752132 · Revista espanola de quimioterapia : publ (2023) — Status of Herpes Zoster and Herpes Zoster Vaccines in 2023: A position paper.
does_not_resolve 33647971 · QJM : monthly journal of the Association (2021) — COVID-19 vaccine-related myositis.
ambiguous 34854882 · Blood (2021) — VITT(al) insights into vaccine-related clots.
does_not_resolve 37775180 · Clinical medicine (London, England) (2023) — SARS-CoV-2 vaccines and myocarditis.
ambiguous 30000765 · (2006) — Human Papillomavirus Vaccines.
ambiguous 36381561 · Public health in practice (Oxford, Engla (2022) — Monkeypox vaccine-related stigma.
A10 · No confounding objectno_data
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: The retrieved evidence contains only case reports of herpes zoster reactivation after COVID-19 vaccine or Shingrix vaccine, with one case describing post-herpetic neuralgia after COVID-19 vaccine; no evidence specifically links Shingles (zoster) vaccine to new post-herpetic neuralgia attributable to the vaccine after excluding co-occurring conditions.
Cited: (none)
supporting: Shingles (zoster) vaccine Post herpetic neuralgia case report OR case series No confounding object
pubmed · 43 hits · run 2026-09-09
mirror: Shingles (zoster) vaccine Post herpetic neuralgia alternative diagnosis OR not vaccine-related
pubmed · 4057 hits · run 2026-09-09
17 retrieved record(s)
supports_node 37052164 · Agri : Agri (Algoloji) Dernegi'nin Yayin (2023) — Inactivated COVID-19 vaccine-related herpes zoster and post-herpetic neuralgia: Three case reports.
supports_node 36874700 · Cureus (2023) — Reactivation of Herpes Zoster After Recombinant Vaccine (Shingrix): A Case Report.
does_not_resolve 36752132 · Revista espanola de quimioterapia : publ (2023) — Status of Herpes Zoster and Herpes Zoster Vaccines in 2023: A position paper.
ambiguous 38721437 · Anesthesiology and pain medicine (2023) — Herpes Zoster Reactivation After COVID-19 Vaccine with Focus on Postherpetic Neuralgia Prevention: A Case Series.
supports_node 41769456 · Cureus (2026) — Herpes Zoster Induced by the Shingrix Vaccine: A Case Report and Literature Review.
does_not_resolve 33647971 · QJM : monthly journal of the Association (2021) — COVID-19 vaccine-related myositis.
ambiguous 34854882 · Blood (2021) — VITT(al) insights into vaccine-related clots.
does_not_resolve 37775180 · Clinical medicine (London, England) (2023) — SARS-CoV-2 vaccines and myocarditis.
D1 · Predicted site of injuryno_data
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 Post herpetic neuralgia anatomic localization Predicted site of injury mechanism
pubmed · 0 hits (0 hits — negative) · run 2026-09-09
mirror: Shingles (zoster) vaccine Post herpetic neuralgia 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
Finding: no evidence found
Cited: (none)
supporting: Shingles (zoster) vaccine Post herpetic neuralgia anatomic localization Spared structures mechanism
pubmed · 0 hits (0 hits — negative) · run 2026-09-09
mirror: Shingles (zoster) vaccine Post herpetic neuralgia 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 Post herpetic neuralgia anatomic localization Local vs systemic distribution mechanism
pubmed · 0 hits (0 hits — negative) · run 2026-09-09
mirror: Shingles (zoster) vaccine Post herpetic neuralgia 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: no evidence found
Cited: (none)
supporting: Shingles (zoster) vaccine Post herpetic neuralgia anatomic localization Kinetics class mechanism
pubmed · 0 hits (0 hits — negative) · run 2026-09-09
mirror: Shingles (zoster) vaccine Post herpetic neuralgia Kinetics class not consistent with mechanism
pubmed · 0 hits (0 hits — negative) · run 2026-09-09
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
Finding: no evidence found
Cited: (none)
supporting: Shingles (zoster) vaccine Post herpetic neuralgia anatomic localization Platform-mechanism match mechanism
pubmed · 0 hits (0 hits — negative) · run 2026-09-09
mirror: Shingles (zoster) vaccine Post herpetic neuralgia 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 Post herpetic neuralgia Targeted treatment reverses intervention OR treatment OR reversal
pubmed · 15145596 hits · run 2026-09-09
mirror: Shingles (zoster) vaccine Post herpetic neuralgia Targeted treatment reverses no effect intervention
pubmed · 1 hits · run 2026-09-09
1 retrieved record(s)
ambiguous 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 Post herpetic neuralgia No internal contradiction coherence OR latency OR susceptibility
pubmed · 870319 hits · run 2026-09-09
mirror: Shingles (zoster) vaccine Post herpetic neuralgia No internal contradiction inconsistent OR contradicts
pubmed · 27616 hits · run 2026-09-09
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 Post herpetic neuralgia Analogy to a known object coherence OR latency OR susceptibility
pubmed · 870319 hits · run 2026-09-09
mirror: Shingles (zoster) vaccine Post herpetic neuralgia 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 Post herpetic neuralgia Latency coherence coherence OR latency OR susceptibility
pubmed · 870319 hits · run 2026-09-09
mirror: Shingles (zoster) vaccine Post herpetic neuralgia Latency coherence inconsistent OR contradicts
pubmed · 27617 hits · run 2026-09-09
J1 · Pre-specificationno_data
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 to detect immune-related adverse events from immune checkpoint inhibitors and AI-based adjudication of major adverse cardiovascular events in clinical trials; neither study addresses post herpetic neuralgia following shingles vaccine.
Cited: (none)
supporting: Shingles (zoster) vaccine Post herpetic neuralgia Pre-specification pre-specified OR adjudicated
pubmed · 13561 hits · run 2026-09-09
mirror: Shingles (zoster) vaccine Post herpetic neuralgia 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: No evidence found.
Cited: (none)
supporting: Shingles (zoster) vaccine Post herpetic neuralgia Contrary-evidence log pre-specified OR adjudicated
pubmed · 13561 hits · run 2026-09-09
mirror: Shingles (zoster) vaccine Post herpetic neuralgia 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: The retrieved evidence discusses the use of large language models and artificial intelligence to identify immune-related adverse events and adjudicate major adverse cardiovascular events, respectively, and does not address any temporal or causal relationship between Shingles (zoster) vaccine and Post herpetic neuralgia.
Cited: (none)
supporting: Shingles (zoster) vaccine Post herpetic neuralgia No temporality-only claim pre-specified OR adjudicated
pubmed · 13561 hits · run 2026-09-09
mirror: Shingles (zoster) vaccine Post herpetic neuralgia No temporality-only claim 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.
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 Post herpetic neuralgia Passive-surveillance role pre-specified OR adjudicated
pubmed · 13561 hits · run 2026-09-09
mirror: Shingles (zoster) vaccine Post herpetic neuralgia Passive-surveillance role 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.
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: No evidence found that maps dose or lot exposure to post herpetic neuralgia cases attributed to shingles vaccine; the retrieved study addresses immune-related adverse events from immune checkpoint inhibitors, not shingles vaccine or post herpetic neuralgia.
Cited: (none)
supporting: Shingles (zoster) vaccine Post herpetic neuralgia Dose mapping pre-specified OR adjudicated
pubmed · 13561 hits · run 2026-09-09
mirror: Shingles (zoster) vaccine Post herpetic neuralgia Dose mapping 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

Epidemiologic chassis 13/13 evaluated

B1 · Excess vs baselineno_data
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: The retrieved evidence includes one SCCS study (PMID 40924159) that found a transient increased risk of shingles post-Shingrix vaccination, but no retrieved study directly addresses excess risk of postherpetic neuralgia following shingles (zoster) vaccination specifically.
Cited: (none)
supporting: Shingles (zoster) vaccine Post herpetic neuralgia Excess vs baseline incidence risk cohort OR self-controlled case series
pubmed · 948 hits · run 2026-09-09
mirror: Shingles (zoster) vaccine Post herpetic neuralgia no association OR null OR no increased risk Excess vs baseline
pubmed · 88702 hits · run 2026-09-09
14 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.
ambiguous 40924159 · Clinical infectious diseases : an offici (2025) — Transient Increased Risk of Shingles Post-Shingrix Vaccination: Self-Controlled Case-Series Analysis.
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 27626517 · The New England journal of medicine (2016) — Efficacy of the Herpes Zoster Subunit Vaccine in Adults 70 Years of Age or Older.
does_not_resolve 38543886 · Vaccines (2024) — Herpes Zoster and Cardiovascular Disease: Exploring Associations and Preventive Measures through Vaccination.
does_not_resolve 31677266 · Clinical infectious diseases : an offici (2020) — Herpes Zoster Risk in Immunocompromised Adults in the United States: A Systematic Review.
B2 · SCCSno_data
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 SCCS analysis found a transient increased risk of shingles (herpes zoster) shortly after Shingrix vaccination, but the retrieved abstract does not report a risk ratio for postherpetic neuralgia following shingles vaccine; no SCCS study in the retrieved evidence directly addresses the pair of shingles vaccine causing postherpetic neuralgia.
Cited: PMID 40924159
supporting: Shingles (zoster) vaccine Post herpetic neuralgia SCCS incidence risk cohort OR self-controlled case series
pubmed · 948 hits · run 2026-09-09
mirror: Shingles (zoster) vaccine Post herpetic neuralgia no association OR null OR no increased risk SCCS
pubmed · 88812 hits · run 2026-09-09
13 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.
refutes_node 40924159 · Clinical infectious diseases : an offici (2025) — Transient Increased Risk of Shingles Post-Shingrix Vaccination: Self-Controlled Case-Series Analysis.
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 27626517 · The New England journal of medicine (2016) — Efficacy of the Herpes Zoster Subunit Vaccine in Adults 70 Years of Age or Older.
does_not_resolve 38543886 · Vaccines (2024) — Herpes Zoster and Cardiovascular Disease: Exploring Associations and Preventive Measures through Vaccination.
does_not_resolve 31677266 · Clinical infectious diseases : an offici (2020) — Herpes Zoster Risk in Immunocompromised Adults in the United States: A Systematic Review.
B3 · Cohort / risk-intervalno_data
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 (not postherpetic neuralgia) immediately post-Shingrix vaccination using an SCCS design, but no retrieved study directly addresses whether shingles vaccination increases the incidence of postherpetic neuralgia (PHN) with an age/sex-stratified IRR >1 and CI excluding 1 in a pre-specified risk window.
Cited: (none)
supporting: Shingles (zoster) vaccine Post herpetic neuralgia Cohort / risk-interval incidence risk cohort OR self-controlled case series
pubmed · 948 hits · run 2026-09-09
mirror: Shingles (zoster) vaccine Post herpetic neuralgia no association OR null OR no increased risk Cohort / risk-interval
pubmed · 88311 hits · run 2026-09-09
13 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.
supports_node 40924159 · Clinical infectious diseases : an offici (2025) — Transient Increased Risk of Shingles Post-Shingrix Vaccination: Self-Controlled Case-Series Analysis.
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 27626517 · The New England journal of medicine (2016) — Efficacy of the Herpes Zoster Subunit Vaccine in Adults 70 Years of Age or Older.
does_not_resolve 38543886 · Vaccines (2024) — Herpes Zoster and Cardiovascular Disease: Exploring Associations and Preventive Measures through Vaccination.
does_not_resolve 31677266 · Clinical infectious diseases : an offici (2020) — Herpes Zoster Risk in Immunocompromised Adults in the United States: A Systematic Review.
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: A systematic review and meta-analysis evaluated the effectiveness of herpes zoster vaccines against postherpetic neuralgia but did not report a pooled estimate >1 with quantified heterogeneity for the vaccine causing postherpetic neuralgia; instead, it assessed vaccine effectiveness in preventing the outcome.
Cited: PMID 36098300
supporting: Shingles (zoster) vaccine Post herpetic neuralgia Meta-analysis / pooling incidence risk cohort OR self-controlled case series
pubmed · 949 hits · run 2026-09-09
mirror: Shingles (zoster) vaccine Post herpetic neuralgia no association OR null OR no increased risk Meta-analysis / pooling
pubmed · 112159 hits · run 2026-09-09
13 retrieved record(s)
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 34937500 · Expert review of vaccines (2022) — Self-controlled case series design in vaccine safety: a systematic review.
refutes_node 40924159 · Clinical infectious diseases : an offici (2025) — Transient Increased Risk of Shingles Post-Shingrix Vaccination: Self-Controlled Case-Series Analysis.
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 27626517 · The New England journal of medicine (2016) — Efficacy of the Herpes Zoster Subunit Vaccine in Adults 70 Years of Age or Older.
does_not_resolve 38543886 · Vaccines (2024) — Herpes Zoster and Cardiovascular Disease: Exploring Associations and Preventive Measures through Vaccination.
does_not_resolve 31677266 · Clinical infectious diseases : an offici (2020) — Herpes Zoster Risk in Immunocompromised Adults in the United States: A Systematic Review.
B5 · Negative-control outcomesno_data
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 does not provide any data on post herpetic neuralgia as a negative-control outcome following shingles vaccination. The only study on shingles vaccination and subsequent outcomes (PMID 40924159) examines increased shingles risk post-RZV vaccination, not post herpetic neuralgia, and no study evaluates the specificity null hypothesis for this negative-control outcome.
Cited: (none)
supporting: Shingles (zoster) vaccine Post herpetic neuralgia Negative-control outcomes incidence risk cohort OR self-controlled case series
pubmed · 948 hits · run 2026-09-09
mirror: Shingles (zoster) vaccine Post herpetic neuralgia no association OR null OR no increased risk Negative-control outcomes
pubmed · 88513 hits · run 2026-09-09
10 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.
refutes_node 40924159 · Clinical infectious diseases : an offici (2025) — Transient Increased Risk of Shingles Post-Shingrix Vaccination: Self-Controlled Case-Series Analysis.
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.
refutes_node 27626517 · The New England journal of medicine (2016) — Efficacy of the Herpes Zoster Subunit Vaccine in Adults 70 Years of Age or Older.
does_not_resolve 38543886 · Vaccines (2024) — Herpes Zoster and Cardiovascular Disease: Exploring Associations and Preventive Measures through Vaccination.
does_not_resolve 31677266 · Clinical infectious diseases : an offici (2020) — Herpes Zoster Risk in Immunocompromised Adults in the United States: A Systematic Review.
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: The retrieved evidence includes a self-controlled case series analysis (PMID 40924159) that investigated transient increased risk of shingles (herpes zoster) post-Shingrix vaccination, but it does not address the node-specific question of Post herpetic neuralgia risk attributable to the shingles vaccine compared with a different-antigen comparator (node B6). Other retrieved studies focus on vaccine efficacy, safety in immunocompromised populations, or general methodology, with none providing a direct comparison of post-herpetic neuralgia risk between shingles vaccine and a different-antigen vaccine.
Cited: (none)
supporting: Shingles (zoster) vaccine Post herpetic neuralgia Other-antigen comparison incidence risk cohort OR self-controlled case series
pubmed · 948 hits · run 2026-09-09
mirror: Shingles (zoster) vaccine Post herpetic neuralgia no association OR null OR no increased risk Other-antigen comparison
pubmed · 88275 hits · run 2026-09-09
13 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.
ambiguous 40924159 · Clinical infectious diseases : an offici (2025) — Transient Increased Risk of Shingles Post-Shingrix Vaccination: Self-Controlled Case-Series Analysis.
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.
refutes_node 27626517 · The New England journal of medicine (2016) — Efficacy of the Herpes Zoster Subunit Vaccine in Adults 70 Years of Age or Older.
does_not_resolve 38543886 · Vaccines (2024) — Herpes Zoster and Cardiovascular Disease: Exploring Associations and Preventive Measures through Vaccination.
does_not_resolve 31677266 · Clinical infectious diseases : an offici (2020) — Herpes Zoster Risk in Immunocompromised Adults in the United States: A Systematic Review.
B7 · Absolute riskno_data
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: No retrieved evidence provides a per-100k absolute risk estimate for new Post herpetic neuralgia attributed to Shingles vaccine within a pre-specified risk window after competing causes are assessed.
Cited: (none)
supporting: Shingles (zoster) vaccine Post herpetic neuralgia Absolute risk incidence risk cohort OR self-controlled case series
pubmed · 949 hits · run 2026-09-09
mirror: Shingles (zoster) vaccine Post herpetic neuralgia no association OR null OR no increased risk Absolute risk
pubmed · 111563 hits · run 2026-09-09
14 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.
supports_node 40924159 · Clinical infectious diseases : an offici (2025) — Transient Increased Risk of Shingles Post-Shingrix Vaccination: Self-Controlled Case-Series Analysis.
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 29211679 · The New England journal of medicine (2017) — Contemporary Hormonal Contraception and the Risk of Breast Cancer.
refutes_node 27626517 · The New England journal of medicine (2016) — Efficacy of the Herpes Zoster Subunit Vaccine in Adults 70 Years of Age or Older.
does_not_resolve 38543886 · Vaccines (2024) — Herpes Zoster and Cardiovascular Disease: Exploring Associations and Preventive Measures through Vaccination.
B8 · Platform splitno_data
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) post-Shingrix (RZV) using SCCS, but does not report postherpetic neuralgia risk. No retrieved study isolates postherpetic neuralgia risk attributable to a specific vaccine platform versus 'a vaccine' generally.
Cited: PMID 40924159
supporting: Shingles (zoster) vaccine Post herpetic neuralgia Platform split incidence risk cohort OR self-controlled case series
pubmed · 948 hits · run 2026-09-09
mirror: Shingles (zoster) vaccine Post herpetic neuralgia no association OR null OR no increased risk Platform split
pubmed · 88340 hits · run 2026-09-09
13 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.
refutes_node 40924159 · Clinical infectious diseases : an offici (2025) — Transient Increased Risk of Shingles Post-Shingrix Vaccination: Self-Controlled Case-Series Analysis.
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.
refutes_node 27626517 · The New England journal of medicine (2016) — Efficacy of the Herpes Zoster Subunit Vaccine in Adults 70 Years of Age or Older.
does_not_resolve 38543886 · Vaccines (2024) — Herpes Zoster and Cardiovascular Disease: Exploring Associations and Preventive Measures through Vaccination.
does_not_resolve 31677266 · Clinical infectious diseases : an offici (2020) — Herpes Zoster Risk in Immunocompromised Adults in the United States: A Systematic Review.
B9 · Host-structure stratificationno_data
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: The retrieved evidence includes no studies that report Post herpetic neuralgia risk by age, sex, or host structure specifically after Shingles (zoster) vaccination; available studies focus on zoster vaccine efficacy, herpes zoster risk in immunocompromised hosts, or methodologic design reviews without providing stratified risk data for this vaccine-outcome pair.
Cited: (none)
supporting: Shingles (zoster) vaccine Post herpetic neuralgia Host-structure stratification incidence risk cohort OR self-controlled case series
pubmed · 948 hits · run 2026-09-09
mirror: Shingles (zoster) vaccine Post herpetic neuralgia no association OR null OR no increased risk Host-structure stratification
pubmed · 88273 hits · run 2026-09-09
12 retrieved record(s)
does_not_resolve 34937500 · Expert review of vaccines (2022) — Self-controlled case series design in vaccine safety: a systematic review.
ambiguous 40924159 · Clinical infectious diseases : an offici (2025) — Transient Increased Risk of Shingles Post-Shingrix Vaccination: Self-Controlled Case-Series Analysis.
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 27626517 · The New England journal of medicine (2016) — Efficacy of the Herpes Zoster Subunit Vaccine in Adults 70 Years of Age or Older.
does_not_resolve 38543886 · Vaccines (2024) — Herpes Zoster and Cardiovascular Disease: Exploring Associations and Preventive Measures through Vaccination.
does_not_resolve 31677266 · Clinical infectious diseases : an offici (2020) — Herpes Zoster Risk in Immunocompromised Adults in the United States: A Systematic Review.
does_not_resolve 15930418 · The New England journal of medicine (2005) — A vaccine to prevent herpes zoster and postherpetic neuralgia in older adults.
B10 · Formulation / component changeno_data
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: No retrieved evidence directly examines a change in postherpetic neuralgia risk that tracks a documented formulation or component change of the shingles vaccine over time.
Cited: (none)
supporting: Shingles (zoster) vaccine Post herpetic neuralgia Formulation / component change incidence risk cohort OR self-controlled case series
pubmed · 948 hits · run 2026-09-09
mirror: Shingles (zoster) vaccine Post herpetic neuralgia no association OR null OR no increased risk Formulation / component change
pubmed · 88435 hits · run 2026-09-09
9 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 40924159 · Clinical infectious diseases : an offici (2025) — Transient Increased Risk of Shingles Post-Shingrix Vaccination: Self-Controlled Case-Series Analysis.
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.
refutes_node 27626517 · The New England journal of medicine (2016) — Efficacy of the Herpes Zoster Subunit Vaccine in Adults 70 Years of Age or Older.
does_not_resolve 38543886 · Vaccines (2024) — Herpes Zoster and Cardiovascular Disease: Exploring Associations and Preventive Measures through Vaccination.
does_not_resolve 31677266 · Clinical infectious diseases : an offici (2020) — Herpes Zoster Risk in Immunocompromised Adults in the United States: A Systematic Review.
supports_node 15930418 · The New England journal of medicine (2005) — A vaccine to prevent herpes zoster and postherpetic neuralgia in older adults.
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 Post herpetic neuralgia Formulation natural experiment intervention OR treatment OR reversal
pubmed · 15145596 hits · run 2026-09-09
mirror: Shingles (zoster) vaccine Post herpetic neuralgia Formulation natural experiment no effect intervention
pubmed · 0 hits (0 hits — negative) · run 2026-09-09
1 retrieved record(s)
does_not_resolve 38189107 · Expert review of vaccines (2024) — Neoadjuvant personalized cancer vaccines: the final frontier?
H4 · Policy / pause signalno_data
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 Post herpetic neuralgia Policy / pause signal intervention OR treatment OR reversal
pubmed · 15145596 hits · run 2026-09-09
mirror: Shingles (zoster) vaccine Post herpetic neuralgia Policy / pause signal no effect intervention
pubmed · 0 hits (0 hits — negative) · run 2026-09-09
1 retrieved record(s)
does_not_resolve 38189107 · Expert review of vaccines (2024) — Neoadjuvant personalized cancer vaccines: the final frontier?
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: no evidence found
Cited: (none)
supporting: Shingles (zoster) vaccine Post herpetic neuralgia Infection coherence coherence OR latency OR susceptibility
pubmed · 870319 hits · run 2026-09-09
mirror: Shingles (zoster) vaccine Post herpetic neuralgia Infection coherence inconsistent OR contradicts
pubmed · 27617 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.

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 evidence found
Cited: (none)
supporting: Shingles (zoster) vaccine Post herpetic neuralgia Dose strength gradient dose-response OR dose effect
pubmed · 1299405 hits · run 2026-09-09
mirror: Shingles (zoster) vaccine Post herpetic neuralgia no dose effect OR no dose-response Dose strength gradient
pubmed · 181 hits · run 2026-09-09
9 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 37967254 · Human vaccines & immunotherapeutics (2023) — Effectiveness and safety of recombinant zoster vaccine: A review of real-world evidence.
does_not_resolve 33580242 · Clinical infectious diseases : an offici (2021) — Recombinant Zoster Vaccine (Shingrix): Real-World Effectiveness in the First 2 Years Post-Licensure.
supports_node 31287523 · JAMA (2019) — Effect of Recombinant Zoster Vaccine on Incidence of Herpes Zoster After Autologous Stem Cell Transplantation: A Randomized Clinical Trial.
does_not_resolve 40581370 · Clinical infectious diseases : an offici (2026) — Effectiveness of the Adjuvanted Recombinant Zoster Vaccine in Adults ≥50 Years in the United States.
does_not_resolve 30028651 · Expert review of vaccines (2018) — Development of adjuvanted recombinant zoster vaccine and its implications for shingles prevention.
does_not_resolve 38504173 · BMC infectious diseases (2024) — Immune response to the recombinant herpes zoster vaccine in people living with HIV over 50 years of age compared to non-HIV age-/gender-matched controls (SHINGR
does_not_resolve 19335725 · Dermatologic therapy (2009) — Varicella zoster vaccines.
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 retrieved evidence addresses a dose-number gradient (1st vs 2nd vs 3rd) for the risk of postherpetic neuralgia attributed to shingles vaccine. Available studies compare one versus two doses of RZV for effectiveness against herpes zoster, but do not define a pattern of increasing risk with dose number, nor do they report postherpetic neuralgia as an adverse event following vaccination.
Cited: (none)
supporting: Shingles (zoster) vaccine Post herpetic neuralgia Dose number gradient dose-response OR dose effect
pubmed · 1299405 hits · run 2026-09-09
mirror: Shingles (zoster) vaccine Post herpetic neuralgia no dose effect OR no dose-response Dose number gradient
pubmed · 625 hits · run 2026-09-09
10 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 37967254 · Human vaccines & immunotherapeutics (2023) — Effectiveness and safety of recombinant zoster vaccine: A review of real-world evidence.
does_not_resolve 33580242 · Clinical infectious diseases : an offici (2021) — Recombinant Zoster Vaccine (Shingrix): Real-World Effectiveness in the First 2 Years Post-Licensure.
does_not_resolve 31287523 · JAMA (2019) — Effect of Recombinant Zoster Vaccine on Incidence of Herpes Zoster After Autologous Stem Cell Transplantation: A Randomized Clinical Trial.
does_not_resolve 40581370 · Clinical infectious diseases : an offici (2026) — Effectiveness of the Adjuvanted Recombinant Zoster Vaccine in Adults ≥50 Years in the United States.
does_not_resolve 30028651 · Expert review of vaccines (2018) — Development of adjuvanted recombinant zoster vaccine and its implications for shingles prevention.
ambiguous 38504173 · BMC infectious diseases (2024) — Immune response to the recombinant herpes zoster vaccine in people living with HIV over 50 years of age compared to non-HIV age-/gender-matched controls (SHINGR
does_not_resolve 19335725 · Dermatologic therapy (2009) — Varicella zoster vaccines.
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: The retrieved evidence does not provide data on risk of postherpetic neuralgia ordered by measured-exposure tertiles of shingles vaccine. No study among the retrieved PMIDs reports vaccine exposure stratified into tertiles or examines a dose-response relationship across tertiles for postherpetic neuralgia.
Cited: (none)
supporting: Shingles (zoster) vaccine Post herpetic neuralgia Measured-exposure tertiles dose-response OR dose effect
pubmed · 1299405 hits · run 2026-09-09
mirror: Shingles (zoster) vaccine Post herpetic neuralgia no dose effect OR no dose-response Measured-exposure tertiles
pubmed · 70 hits · run 2026-09-09
11 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 37967254 · Human vaccines & immunotherapeutics (2023) — Effectiveness and safety of recombinant zoster vaccine: A review of real-world evidence.
does_not_resolve 33580242 · Clinical infectious diseases : an offici (2021) — Recombinant Zoster Vaccine (Shingrix): Real-World Effectiveness in the First 2 Years Post-Licensure.
does_not_resolve 31287523 · JAMA (2019) — Effect of Recombinant Zoster Vaccine on Incidence of Herpes Zoster After Autologous Stem Cell Transplantation: A Randomized Clinical Trial.
refutes_node 40581370 · Clinical infectious diseases : an offici (2026) — Effectiveness of the Adjuvanted Recombinant Zoster Vaccine in Adults ≥50 Years in the United States.
does_not_resolve 30028651 · Expert review of vaccines (2018) — Development of adjuvanted recombinant zoster vaccine and its implications for shingles prevention.
does_not_resolve 38504173 · BMC infectious diseases (2024) — Immune response to the recombinant herpes zoster vaccine in people living with HIV over 50 years of age compared to non-HIV age-/gender-matched controls (SHINGR
does_not_resolve 19335725 · Dermatologic therapy (2009) — Varicella zoster vaccines.
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 retrieved evidence addresses a dose-dependent effect of shingles vaccine across a graded concentration curve in organoids, or provides any data on antigen concentration versus effect in an organoid model for postherpetic neuralgia.
Cited: (none)
supporting: Shingles (zoster) vaccine Post herpetic neuralgia Organoid concentration curve dose-response OR dose effect
pubmed · 1299405 hits · run 2026-09-09
mirror: Shingles (zoster) vaccine Post herpetic neuralgia no dose effect OR no dose-response Organoid concentration curve
pubmed · 81 hits · run 2026-09-09
10 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 37967254 · Human vaccines & immunotherapeutics (2023) — Effectiveness and safety of recombinant zoster vaccine: A review of real-world evidence.
does_not_resolve 33580242 · Clinical infectious diseases : an offici (2021) — Recombinant Zoster Vaccine (Shingrix): Real-World Effectiveness in the First 2 Years Post-Licensure.
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 40581370 · Clinical infectious diseases : an offici (2026) — Effectiveness of the Adjuvanted Recombinant Zoster Vaccine in Adults ≥50 Years in the United States.
does_not_resolve 30028651 · Expert review of vaccines (2018) — Development of adjuvanted recombinant zoster vaccine and its implications for shingles prevention.
does_not_resolve 38504173 · BMC infectious diseases (2024) — Immune response to the recombinant herpes zoster vaccine in people living with HIV over 50 years of age compared to non-HIV age-/gender-matched controls (SHINGR
does_not_resolve 19335725 · Dermatologic therapy (2009) — Varicella zoster vaccines.
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: The retrieved evidence includes real-world studies on recombinant zoster vaccine (RZV) effectiveness and safety, and a self-controlled case series analysis suggesting a transient increased risk of shingles shortly after RZV vaccination, but no retrieved study provides pharmacokinetic data (e.g., Cmax/tissue levels) or in-vitro EC50 values for RZV or any shingles vaccine that would allow assessment of whether achieved exposure plausibly reaches an in-vitro EC50 threshold. No evidence linking exposure measures to in-vitro effect thresholds for postherpetic neuralgia was found.
Cited: (none)
supporting: Shingles (zoster) vaccine Post herpetic neuralgia EC50 vs Cmax coherence dose-response OR dose effect
pubmed · 1299405 hits · run 2026-09-09
mirror: Shingles (zoster) vaccine Post herpetic neuralgia no dose effect OR no dose-response EC50 vs Cmax coherence
pubmed · 70 hits · run 2026-09-09
10 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 37967254 · Human vaccines & immunotherapeutics (2023) — Effectiveness and safety of recombinant zoster vaccine: A review of real-world evidence.
does_not_resolve 33580242 · Clinical infectious diseases : an offici (2021) — Recombinant Zoster Vaccine (Shingrix): Real-World Effectiveness in the First 2 Years Post-Licensure.
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 40581370 · Clinical infectious diseases : an offici (2026) — Effectiveness of the Adjuvanted Recombinant Zoster Vaccine in Adults ≥50 Years in the United States.
does_not_resolve 30028651 · Expert review of vaccines (2018) — Development of adjuvanted recombinant zoster vaccine and its implications for shingles prevention.
does_not_resolve 38504173 · BMC infectious diseases (2024) — Immune response to the recombinant herpes zoster vaccine in people living with HIV over 50 years of age compared to non-HIV age-/gender-matched controls (SHINGR
does_not_resolve 19335725 · Dermatologic therapy (2009) — Varicella zoster vaccines.
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 evidence found
Cited: (none)
supporting: Shingles (zoster) vaccine Post herpetic neuralgia mechanism Mediator identified in cases in vitro OR patient-derived
pubmed · 29262 hits · run 2026-09-09
mirror: Shingles (zoster) vaccine Post herpetic neuralgia Mediator identified in cases not associated mechanism
pubmed · 2 hits · run 2026-09-09
2 retrieved record(s)
does_not_resolve 31287523 · JAMA (2019) — Effect of Recombinant Zoster Vaccine on Incidence of Herpes Zoster After Autologous Stem Cell Transplantation: A Randomized Clinical Trial.
does_not_resolve 41081504 · Journal of medical virology (2025) — Epidemiology and Clinical Profile of Herpes Zoster in the Varicella Vaccine Era: A Case Series Study.
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: no evidence found
Cited: (none)
supporting: Shingles (zoster) vaccine Post herpetic neuralgia mechanism Mediator in healthy vaccinees in vitro OR patient-derived
pubmed · 29262 hits · run 2026-09-09
mirror: Shingles (zoster) vaccine Post herpetic neuralgia Mediator in healthy vaccinees not associated mechanism
pubmed · 0 hits (0 hits — negative) · run 2026-09-09
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: The retrieved evidence shows that VZV-specific cell-mediated immunity correlates inversely with herpes zoster incidence and severity, but does not compare vaccination to natural infection regarding postherpetic neuralgia. A second study indicates that wild-type VZV, but not the vaccine strain, induces sensitivity to adrenergic stimulation in sensory neurons, which is relevant to postherpetic neuralgia mechanisms, yet no direct comparison of mediator presence or absence after natural infection versus vaccination is provided.
Cited: PMID 31543415 PMID 12627494
supporting: Shingles (zoster) vaccine Post herpetic neuralgia mechanism Infection contrast in vitro OR patient-derived
pubmed · 29262 hits · run 2026-09-09
mirror: Shingles (zoster) vaccine Post herpetic neuralgia Infection contrast not associated mechanism
pubmed · 6 hits · run 2026-09-09
2 retrieved record(s)
ambiguous 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
ambiguous 12627494 · Journal of medical virology (2003) — Varicella-zoster virus isolates, but not the vaccine strain OKA, induce sensitivity to alpha-1 and beta-1 adrenergic stimulation of sensory neurones in culture.
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 Post herpetic neuralgia mechanism Transfer to recipient in vitro OR patient-derived
pubmed · 29262 hits · run 2026-09-09
mirror: Shingles (zoster) vaccine Post herpetic neuralgia Transfer to recipient not associated mechanism
pubmed · 0 hits (0 hits — negative) · 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: no evidence found
Cited: (none)
supporting: Shingles (zoster) vaccine Post herpetic neuralgia mechanism Transfer specificity in vitro OR patient-derived
pubmed · 29262 hits · run 2026-09-09
mirror: Shingles (zoster) vaccine Post herpetic neuralgia Transfer specificity not associated mechanism
pubmed · 0 hits (0 hits — negative) · run 2026-09-09
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 Post herpetic neuralgia mechanism Depletion / knockdown in vitro OR patient-derived
pubmed · 29262 hits · run 2026-09-09
mirror: Shingles (zoster) vaccine Post herpetic neuralgia Depletion / knockdown not associated mechanism
pubmed · 0 hits (0 hits — negative) · run 2026-09-09
E7 · Add-back rescueno_data
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 Post herpetic neuralgia mechanism Add-back rescue in vitro OR patient-derived
pubmed · 29262 hits · run 2026-09-09
mirror: Shingles (zoster) vaccine Post herpetic neuralgia Add-back rescue not associated mechanism
pubmed · 0 hits (0 hits — negative) · run 2026-09-09
E8 · Neutralizationno_data
Measure: Neutralizing the mediator blocks the effect
Comparator: Isotype control
Hit rule: Neutralization of the mediator (not an isotype control) blocks the phenotype
Finding: The retrieved evidence describes preclinical studies of shingles vaccine formulations and their immune responses in mice, but does not investigate neutralization of a mediator that blocks postherpetic neuralgia.
Cited: (none)
supporting: Shingles (zoster) vaccine Post herpetic neuralgia mechanism Neutralization in vitro OR patient-derived
pubmed · 29262 hits · run 2026-09-09
mirror: Shingles (zoster) vaccine Post herpetic neuralgia Neutralization not associated mechanism
pubmed · 5 hits · run 2026-09-09
2 retrieved record(s)
does_not_resolve 32167678 · Immunity, inflammation and disease (2020) — Evaluation of glycoprotein E subunit and live attenuated varicella-zoster virus vaccines formulated with a single-strand RNA-based adjuvant.
does_not_resolve 35455278 · Vaccines (2022) — Enhanced Potency and Persistence of Immunity to Varicella-Zoster Virus Glycoprotein E in Mice by Addition of a Novel BC02 Compound Adjuvant.
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 evidence found
Cited: (none)
supporting: Shingles (zoster) vaccine Post herpetic neuralgia mechanism Isotype control in vitro OR patient-derived
pubmed · 29262 hits · run 2026-09-09
mirror: Shingles (zoster) vaccine Post herpetic neuralgia Isotype control not associated mechanism
pubmed · 1 hits · run 2026-09-09
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 evidence found
Cited: (none)
supporting: Shingles (zoster) vaccine Post herpetic neuralgia Full product reproduces component OR antigen OR vector
pubmed · 2045628 hits · run 2026-09-09
mirror: Shingles (zoster) vaccine Post herpetic neuralgia Full product reproduces no effect component isolation
pubmed · 0 hits (0 hits — negative) · run 2026-09-09
9 retrieved record(s)
does_not_resolve 20218334 · Uirusu (2009) — [Measles vaccine].
does_not_resolve 30917500 · Viruses (2019) — Innovation in Newcastle Disease Virus Vectored Avian Influenza Vaccines.
does_not_resolve 16914237 · Vaccine (2007) — Viral vectors for malaria vaccine development.
does_not_resolve 40857335 · PLoS neglected tropical diseases (2025) — Novel rabies vaccine candidates development based on pseudotyped lentiviral vectors with rabies virus glycoprotein.
does_not_resolve 34816398 · Methods in molecular biology (Clifton, N (2022) — Avian Paramyxoviruses as Vectors for Vaccine Development.
does_not_resolve 33640142 · Vaccine (2022) — Biosecurity risks associated with vaccine platform technologies.
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: no evidence found
Cited: (none)
supporting: Shingles (zoster) vaccine Post herpetic neuralgia Empty vector / particle component OR antigen OR vector
pubmed · 2045628 hits · run 2026-09-09
mirror: Shingles (zoster) vaccine Post herpetic neuralgia Empty vector / particle no effect component isolation
pubmed · 0 hits (0 hits — negative) · run 2026-09-09
9 retrieved record(s)
does_not_resolve 20218334 · Uirusu (2009) — [Measles vaccine].
does_not_resolve 30917500 · Viruses (2019) — Innovation in Newcastle Disease Virus Vectored Avian Influenza Vaccines.
does_not_resolve 16914237 · Vaccine (2007) — Viral vectors for malaria vaccine development.
does_not_resolve 40857335 · PLoS neglected tropical diseases (2025) — Novel rabies vaccine candidates development based on pseudotyped lentiviral vectors with rabies virus glycoprotein.
does_not_resolve 34816398 · Methods in molecular biology (Clifton, N (2022) — Avian Paramyxoviruses as Vectors for Vaccine Development.
does_not_resolve 33640142 · Vaccine (2022) — Biosecurity risks associated with vaccine platform technologies.
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.
F3 · Antigen alone reproducesno_data
Measure: Isolated antigen reproduces the effect
Comparator: Vehicle
Hit rule: The isolated antigen (not the full product) reproduces the effect
Finding: no evidence found
Cited: (none)
supporting: Shingles (zoster) vaccine Post herpetic neuralgia Antigen alone reproduces component OR antigen OR vector
pubmed · 2045628 hits · run 2026-09-09
mirror: Shingles (zoster) vaccine Post herpetic neuralgia Antigen alone reproduces no effect component isolation
pubmed · 0 hits (0 hits — negative) · run 2026-09-09
9 retrieved record(s)
does_not_resolve 20218334 · Uirusu (2009) — [Measles vaccine].
does_not_resolve 16914237 · Vaccine (2007) — Viral vectors for malaria vaccine development.
does_not_resolve 40857335 · PLoS neglected tropical diseases (2025) — Novel rabies vaccine candidates development based on pseudotyped lentiviral vectors with rabies virus glycoprotein.
does_not_resolve 34816398 · Methods in molecular biology (Clifton, N (2022) — Avian Paramyxoviruses as Vectors for Vaccine Development.
does_not_resolve 33640142 · Vaccine (2022) — Biosecurity risks associated with vaccine platform technologies.
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 includes no studies or reports linking shingles (zoster) vaccine to post-herpetic neuralgia; all retrieved PMIDs address unrelated vaccine development topics (measles, malaria, rabies, avian paramyxoviruses, DNA vaccines, bacterial vectors, capripoxviruses, enterovirus D68).
Cited: (none)
supporting: Shingles (zoster) vaccine Post herpetic neuralgia Irrelevant cargo component OR antigen OR vector
pubmed · 2045628 hits · run 2026-09-09
mirror: Shingles (zoster) vaccine Post herpetic neuralgia Irrelevant cargo no effect component isolation
pubmed · 0 hits (0 hits — negative) · run 2026-09-09
9 retrieved record(s)
does_not_resolve 20218334 · Uirusu (2009) — [Measles vaccine].
does_not_resolve 16914237 · Vaccine (2007) — Viral vectors for malaria vaccine development.
does_not_resolve 40857335 · PLoS neglected tropical diseases (2025) — Novel rabies vaccine candidates development based on pseudotyped lentiviral vectors with rabies virus glycoprotein.
does_not_resolve 34816398 · Methods in molecular biology (Clifton, N (2022) — Avian Paramyxoviruses as Vectors for Vaccine Development.
does_not_resolve 33640142 · Vaccine (2022) — Biosecurity risks associated with vaccine platform technologies.
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 Post herpetic neuralgia Infection preparation component OR antigen OR vector
pubmed · 2045629 hits · run 2026-09-09
mirror: Shingles (zoster) vaccine Post herpetic neuralgia Infection preparation no effect component isolation
pubmed · 0 hits (0 hits — negative) · run 2026-09-09
9 retrieved record(s)
does_not_resolve 20218334 · Uirusu (2009) — [Measles vaccine].
does_not_resolve 30917500 · Viruses (2019) — Innovation in Newcastle Disease Virus Vectored Avian Influenza Vaccines.
does_not_resolve 16914237 · Vaccine (2007) — Viral vectors for malaria vaccine development.
does_not_resolve 40857335 · PLoS neglected tropical diseases (2025) — Novel rabies vaccine candidates development based on pseudotyped lentiviral vectors with rabies virus glycoprotein.
does_not_resolve 34816398 · Methods in molecular biology (Clifton, N (2022) — Avian Paramyxoviruses as Vectors for Vaccine Development.
does_not_resolve 33640142 · Vaccine (2022) — Biosecurity risks associated with vaccine platform technologies.
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.
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 Post herpetic neuralgia Cytokine / adjuvant mix component OR antigen OR vector
pubmed · 2045628 hits · run 2026-09-09
mirror: Shingles (zoster) vaccine Post herpetic neuralgia Cytokine / adjuvant mix no effect component isolation
pubmed · 0 hits (0 hits — negative) · run 2026-09-09
9 retrieved record(s)
does_not_resolve 20218334 · Uirusu (2009) — [Measles vaccine].
does_not_resolve 16914237 · Vaccine (2007) — Viral vectors for malaria vaccine development.
does_not_resolve 40857335 · PLoS neglected tropical diseases (2025) — Novel rabies vaccine candidates development based on pseudotyped lentiviral vectors with rabies virus glycoprotein.
does_not_resolve 34816398 · Methods in molecular biology (Clifton, N (2022) — Avian Paramyxoviruses as Vectors for Vaccine Development.
does_not_resolve 33640142 · Vaccine (2022) — Biosecurity risks associated with vaccine platform technologies.
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.
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 evidence found
Cited: (none)
supporting: Shingles (zoster) vaccine Post herpetic neuralgia Component combination component OR antigen OR vector
pubmed · 2045628 hits · run 2026-09-09
mirror: Shingles (zoster) vaccine Post herpetic neuralgia Component combination no effect component isolation
pubmed · 0 hits (0 hits — negative) · run 2026-09-09
9 retrieved record(s)
does_not_resolve 20218334 · Uirusu (2009) — [Measles vaccine].
does_not_resolve 16914237 · Vaccine (2007) — Viral vectors for malaria vaccine development.
does_not_resolve 40857335 · PLoS neglected tropical diseases (2025) — Novel rabies vaccine candidates development based on pseudotyped lentiviral vectors with rabies virus glycoprotein.
does_not_resolve 34816398 · Methods in molecular biology (Clifton, N (2022) — Avian Paramyxoviruses as Vectors for Vaccine Development.
does_not_resolve 33640142 · Vaccine (2022) — Biosecurity risks associated with vaccine platform technologies.
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.
G1 · 2D human cellsno_data
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 Post herpetic neuralgia 2D human cells animal OR organoid OR cell model
pubmed · 1819226 hits · run 2026-09-09
mirror: Shingles (zoster) vaccine Post herpetic neuralgia 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 Post herpetic neuralgia Organoid / chip animal OR organoid OR cell model
pubmed · 1819226 hits · run 2026-09-09
mirror: Shingles (zoster) vaccine Post herpetic neuralgia 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 Post herpetic neuralgia Block in vitro / in vivo intervention OR treatment OR reversal
pubmed · 15145596 hits · run 2026-09-09
mirror: Shingles (zoster) vaccine Post herpetic neuralgia 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 Post herpetic neuralgia mechanism Host-line dependence in vitro OR patient-derived
pubmed · 29262 hits · run 2026-09-09
mirror: Shingles (zoster) vaccine Post herpetic neuralgia Host-line dependence not associated mechanism
pubmed · 0 hits (0 hits — negative) · run 2026-09-09
G3 · Animal, clinical routeno_data
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: no evidence found
Cited: (none)
supporting: Shingles (zoster) vaccine Post herpetic neuralgia Animal, clinical route animal OR organoid OR cell model
pubmed · 1819226 hits · run 2026-09-09
mirror: Shingles (zoster) vaccine Post herpetic neuralgia Animal, clinical route not reproduced model
pubmed · 0 hits (0 hits — negative) · run 2026-09-09
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
Cited: (none)
supporting: Shingles (zoster) vaccine Post herpetic neuralgia Susceptible animal animal OR organoid OR cell model
pubmed · 1819228 hits · run 2026-09-09
mirror: Shingles (zoster) vaccine Post herpetic neuralgia Susceptible animal not reproduced model
pubmed · 2 hits · run 2026-09-09
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 Post herpetic neuralgia Replication across labs animal OR organoid OR cell model
pubmed · 1819226 hits · run 2026-09-09
mirror: Shingles (zoster) vaccine Post herpetic neuralgia 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: no evidence found
Cited: (none)
supporting: Shingles (zoster) vaccine Post herpetic neuralgia Blinded scoring animal OR organoid OR cell model
pubmed · 1819226 hits · run 2026-09-09
mirror: Shingles (zoster) vaccine Post herpetic neuralgia Blinded scoring not reproduced model
pubmed · 0 hits (0 hits — negative) · run 2026-09-09
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 Post herpetic neuralgia Experimental time course animal OR organoid OR cell model
pubmed · 1819226 hits · run 2026-09-09
mirror: Shingles (zoster) vaccine Post herpetic neuralgia Experimental time course not reproduced model
pubmed · 0 hits (0 hits — negative) · 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: The retrieved evidence discusses epigenetic programming in the context of adverse nutritional and diabetic intrauterine environments and later metabolic disease susceptibility, but does not address host traits or markers that enrich for susceptibility to post herpetic neuralgia following shingles vaccine.
Cited: (none)
supporting: Shingles (zoster) vaccine Post herpetic neuralgia Susceptibility trait coherence OR latency OR susceptibility
pubmed · 870319 hits · run 2026-09-09
mirror: Shingles (zoster) vaccine Post herpetic neuralgia 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.