Evidence state
For each outcome: the specific question, what controlled studies found, and how certain that evidence is on the GRADE scale (high, moderate, low, very low). Ratings are editorial judgments by the site applying GRADE to the studies in the table below — observational evidence starts at low and is rated up for large, consistent effects or a dose/age gradient, and down for inconsistency or imprecision (Methods). Where an effect is confined to a subgroup (for example young males), the question says so. "Not searched" means no controlled study has been compiled here yet; it is not a finding that the outcome is rare or caused by the vaccine.
| Outcome & question | Finding & certainty | Why this rating |
|---|---|---|
| Guillain-Barré syndrome Shingrix (RZV), adults 65+ | increased risk (about 3 extra cases per million doses) Low certainty | Start low; +1 RR 2.3–2.8 in two designs; −1 both from one Medicare data source. Studies: Goud 2021. See table |
| Anaphylaxis | Not searched | No controlled-study result is compiled for this outcome yet. |
| Myocarditis or pericarditis | Not searched | No controlled-study result is compiled for this outcome yet. |
| Febrile seizure | Not searched | No controlled-study result is compiled for this outcome yet. |
| Immune thrombocytopenia | Not searched | No controlled-study result is compiled for this outcome yet. |
1. Basic Information
Shingles (herpes zoster) is reactivation of varicella-zoster virus, typically causing painful dermatomal rash. Shingrix (GSK, recombinant adjuvanted, 2-dose series) replaced live Zostavax in U.S. recommendations. Distinct from the childhood varicella (chickenpox) vaccine.
| Product | Status (U.S.) | Schedule |
|---|---|---|
| Shingrix | Preferred; ages ≥50 and immunocompromised indications | 2 doses, 2–6 months apart |
| Zostavax (live) | Withdrawn from U.S. market (2020) | Historical single dose |
Licensed Shingles (Zoster) vaccine products
Each product has its own page with package-insert ingredients, side-effect data, lot lookup and comparisons with the other brands.
- Shingrix — GlaxoSmithKline Biologicalsrecombinant protein; intramuscular; adjuvant: AS01B
Ingredients (Package Insert)
Structured composition for 1 branded product covered on this page, taken from FDA-approved package inserts (DailyMed / manufacturer prescribing information). Lists are per product — formulations differ by manufacturer and presentation. Click an ingredient name to open its safety-context page when available.
Shingrix GlaxoSmithKline Biologicals · Recombinant protein
Delivery
Route: Intramuscular (IM)
Form: Lyophilized powder (reconstitute)
Dose volume: 0.5 mL
Presentation: antigen vial + AS01B adjuvant suspension vial
Encapsulation / delivery vehicle
Liposome — AS01B adjuvant is a liposomal formulation containing MPL and QS-21.
| Component | Role | Amount |
|---|---|---|
| DOPC (dioleoyl phosphatidylcholine) | liposomal phospholipid | label quantity |
| Cholesterol | cholesterol | label quantity |
Antigens
| Antigen | Type | Amount / dose |
|---|---|---|
| Recombinant varicella-zoster virus glycoprotein E (gE) System: CHO cells | Recombinant protein | 50 mcg |
Adjuvants
- AS01B — MPL 50 mcg + QS-21 50 mcg per dose
- MPL (3-O-desacyl-4'-monophosphoryl lipid A) — 50 mcg
- QS-21 (Quillaja saponaria Molina, fraction 21) — 50 mcg
Preservatives
- None — Single-dose presentation; label states no preservative.
Excipients & residuals
| Ingredient | Category | Amount | Role |
|---|---|---|---|
| Sucrose | Stabilizer | label quantity | stabilizer |
| Polysorbate 80 | Surfactant | label quantity | surfactant |
| Sodium dihydrogen phosphate dihydrate / dipotassium phosphate | Buffer | label quantity | buffer |
| Sodium chloride | Buffer | label quantity | tonicity |
Source: FDA package insert · Verified 2026-07-09
ⓘ How to read this section
Ingredient lists are sourced from official package inserts for the specific brands named above. Formulations can change between lots and over time — verify against the current label before any clinical decision. Presence of a substance does not by itself indicate harm; toxicology is dose-, route-, and context-dependent. Browse the full ingredient database: Vaccine Ingredients index.
Causality assessment & potential mechanisms
Conditions below combine WHO-style causality levels with potential biological mechanisms from the site mechanism catalog (ae_mechanisms_catalog.json). HRSA VICP table listing (where shown) indicates a compensable temporal association under U.S. program rules — not automatic proof of causation for every case. Mechanisms are hypothesis-level pathways with graded evidence.
| Condition | Time window | Causality | Potential mechanism(s) |
|---|---|---|---|
| Anaphylaxis | 0–1 days |
Very likely / Probable
Evidence: High |
IgE-mediated hypersensitivity (anaphylaxis) (primary · hypersensitivity) Pre-existing or newly formed IgE against vaccine antigens or excipients (e.g., gelatin, egg proteins, PEG, polysorbate) triggers mast-cell and basophil degranulation with systemic mediator release. |
| Intense local/systemic reactogenicity | 0–3 days |
Very likely / Probable
Evidence: High |
Adjuvant-driven local and systemic reactogenicity (primary · innate_inflammation) Aluminum or other adjuvants (e.g., AS01B) amplify innate immune signaling, producing injection-site inflammation and transient systemic symptoms (fever, myalgia, fatigue). |
| SIRVA | 0–2 days |
Very likely / Probable
Evidence: High |
SIRVA — incorrect injection into shoulder structures (primary · procedural) Needle placement into the subdeltoid/subacromial bursa or joint rather than deltoid muscle causes prolonged local inflammation and restricted range of motion (procedural, not antigen-specific). |
| Guillain-Barré Syndrome | 0–42 days |
Unclassifiable
Evidence: Very Low |
Molecular mimicry → Guillain-Barré syndrome (hypothetical · molecular_mimicry) Vaccine- or infection-triggered immune responses cross-react with peripheral-nerve gangliosides or myelin components, producing demyelinating or axonal polyneuropathy. Temporal association — mechanism unknown (alternative · unknown) Reports show temporal clustering after vaccination but a specific pathogenic pathway is not established; alternative (coincidental) explanations remain plausible. |
Framework: WHO causality + HRSA VICP (where applicable) + AE mechanism catalog.
Last updated: 2026-07-18.
Schema: schemas/vaccine_injury_table.schema.json
· Mechanisms: schemas/ae_mechanism.schema.json.
Not medical or legal advice.
Rank-aggregated VAERS signal detection (rankv)
The table below lists vaccine–event pairs that were detected as disproportionality signals by all four base methods used in rankv (GPS, PRR, ROR, BCPNN) on multi-decade VAERS data, then ordered by rank aggregation (Borda average rank; related to the Spearman/GA top-list approach in the rankv paper).
| Agg. rank | VAERS product | Preferred term (event) | N | Method ranks (GPS / PRR / ROR / BCPNN) |
|---|---|---|---|---|
| 101 | ZOSTER LIVE (ZOSTAVAX) |
Post herpetic neuralgia
clinical-coded PT
|
139 | GPS rank 279 (EBGM=6.04); PRR rank 60 (PRR=100.1631); ROR rank 60 (ROR=100.324); BCPNN rank 52 (IC_LB=4.2626) |
| 139 | ZOSTER LIVE (ZOSTAVAX) |
Herpes zoster
clinical-coded PT
|
3994 | GPS rank 243 (EBGM=5.88); PRR rank 133 (PRR=26.1159); ROR rank 132 (ROR=27.3422); BCPNN rank 71 (IC_LB=3.9432) |
| 247 | ZOSTER (SHINGRIX) |
Incomplete course of vaccination
clinical-coded PT
|
112 | GPS rank 288 (EBGM=6.05); PRR rank 199 (PRR=17.7653); ROR rank 201 (ROR=17.7821); BCPNN rank 209 (IC_LB=3.0726) |
Showing up to 15 pairs for this page (clinical-coded terms listed first).
Full processed tables: rankv_signals.json.
- Methods combined: BCPNN (IC), GPS/EBGM, PRR, ROR — then rank aggregation.
- Data: ~30 years of public VAERS (rankv processed tables).
- Origin: precisionFDA “Gaining New Insights by Detecting Adverse Event Anomalies” challenge solution.
- Caveat: Disproportionality signals are statistical associations in spontaneous reports. They do not establish causality, incidence, or product defect. Many top pairs reflect administration/product-use coding rather than clinical injury.
Source: nanx.me/rankv · Code: github.com/nanxstats/rankv (MIT) · Built: 2026-07-30.
2. Pre-Licensure Clinical Trial Data (Shingrix)
Licensure trial design (ICAN / OpenVAERS)
This vaccine is not listed in ICAN’s childhood-schedule No Placebo Table (which covers CDC routine pediatric injectable products). Pre-licensure trial comparators for travel, adult, or specialty vaccines should be taken from FDA review documents and product labels in the sections below.
Source: OpenVAERS — No Placebo Table · ICAN original PDF · Attribution: Informed Consent Action Network (ICAN) via OpenVAERS · Last fetched: 2026-07-16. For many trials listing '6 months' safety review, ICAN notes review was typically ~30 days post-injection with a phone call at 6 months.
Pivotal trials ZOE-50 (≥50 years) and ZOE-70 (≥70 years) demonstrated high efficacy against shingles and post-herpetic neuralgia vs. placebo.
| Endpoint | ZOE-50 (~15,400 per arm) | ZOE-70 |
|---|---|---|
| Shingles incidence reduction | ~97% (overall; sustained in follow-up) | ~90% in ≥70 |
| Post-herpetic neuralgia | ~89% reduction vs. placebo | Significant reduction vs. placebo |
Most common solicited reactions (pooled trials)
| Reaction | Dose 1 (approx.) | Dose 2 (approx.) |
|---|---|---|
| Injection-site pain | ~78% | ~72% |
| Myalgia | ~45% | ~38% |
| Fatigue | ~45% | ~38% |
| Headache | ~38% | ~32% |
| Shivering / fever | ~15–27% | Lower than dose 1 |
Source: Shingrix prescribing information (FDA); ZOE trial publications. Grade 3 systemic symptoms were uncommon (<3%).
3. Post-Licensure Safety Data
Shingrix has one of the highest VAERS report volumes among non-COVID adult vaccines — consistent with intense reactogenicity in trials and broad age ≥50 rollout. What databases report below is not the same as trial reactogenicity rates.
Passive Surveillance: AE Type Breakdown (Multi-System)
Side-by-side view of U.S. VAERS, Health Canada Canada Vigilance, Japan JADER (PMDA), EU EudraVigilance, and live-scraped international systems via SurVigilance (VigiAccess, Lareb, DAEN, DMA, Medsafe). SurVigilance panels show MedDRA PT mention totals (not individual-case counts). Category assignment uses keyword matching — approximate, not official SOC coding. VAERS files on this site are built from the public VAERS download. FAERS figures use the public quarterly FAERS files. Counts are mentions or reports, not incidence.
VAERS (United States)
No VAERS category summary is mapped for this vaccine page.
Canada Vigilance (Canada)
No matching vaccine reports in the current Canada Vigilance extract.
JADER (PMDA, Japan)
No matching vaccine reports in the current JADER public extract.
EudraVigilance (EU)
No matching vaccine cases in the current EudraVigilance DAP export.
SurVigilance: VigiAccess · Lareb · DAEN · DMA · Medsafe
VigiAccess (WHO)
This system’s totals are not in this panel. Published counts, when this site has them, are in the surveillance section.
Lareb (Netherlands)
This system’s totals are not in this panel. Published counts, when this site has them, are in the surveillance section.
DAEN (Australia)
This system’s totals are not in this panel. Published counts, when this site has them, are in the surveillance section.
DMA (Denmark)
Denmark DMA interactive ADR search is currently offline (Danish Medicines Agency IT transition; public overviews frozen at 12 Mar 2024). Live product PT tables cannot be retrieved until DKMA restores the search. See DKMA notice. Denmark continues to report into EU EudraVigilance (panel above).
Medsafe (New Zealand)
Compare AE patterns across all vaccines →
VAERS Lot-Level Reports
42,821 VAERS reports with usable lot data (U.S.). Signal flags are hypothesis-generating only — not proof of an unsafe lot. Full dashboard →
What controlled safety studies found
Unlike VAERS counts, these studies compare vaccinated people with a control group or control time window, so they can estimate whether a risk is raised and by how much. 4 results for shingles vaccines: 2 found an increased risk of a specific outcome, 1 found no increased risk.
| Outcome | Design & population | Estimate (95% CI) | Excess per million doses | Finding | Source |
|---|---|---|---|---|---|
Guillain-Barre syndrome Shingrix (RZV) | SCCS, claims-based (FDA/CMS Medicare) Medicare beneficiaries >=65 y, US 2017-2020 | IRR 2.84 (1.53–5.27) | 3 | increased risk | Goud R et al., 2021, JAMA Intern Med doi:10.1001/jamainternmed.2021.6227; PMID 34724025 |
Guillain-Barre syndrome Shingrix (RZV) vs Zostavax (ZVL) | cohort (Medicare) Medicare beneficiaries >=65 y, US (849,397 RZV; 1,817,099 ZVL) | RR 2.34 (1.01–5.41) | — | increased risk | Goud R et al., 2021, JAMA Intern Med doi:10.1001/jamainternmed.2021.6227; PMID 34724025 |
10 prespecified outcomes incl. stroke, anaphylaxis, GBS Shingrix (RZV) | sequential surveillance vs historical Zostavax and concurrent comparators (VSD) Adults >=50 y, US 2018-2019 (647,833 doses) | — | — | inconclusive | Nelson JC et al., 2023, Am J Epidemiol doi:10.1093/aje/kwac170; PMID 36193854 |
Any diagnosis (tree-temporal data mining) Shingrix (RZV) | self-controlled tree-temporal scan (MarketScan) Commercially insured adults >=50 y, US (1,014,329 doses) | — | — | no increased risk detected | Yih WK et al., 2022, Am J Epidemiol doi:10.1093/aje/kwac030; PMID 35152283 |
Benefit and risk on the same scale (per million)
Bars are drawn to scale within each comparison. Disease risks are per case of the disease; vaccine risks are the excess above background per dose, from controlled studies. How likely someone is to catch the disease, without vaccination, decides how these weigh up for an individual.
No single study measured both risks in the same population for this vaccine, so no side-by-side ratio is shown; the two lists below come from different studies, eras and populations.
Serious outcomes of the disease (per million cases)
| Herpes zoster: Postherpetic neuralgia | 330,000 | Adults aged >=79 years with HZ, Olmsted County · https://doi.org/10.4065/82.11.1341 |
| Herpes zoster: Postherpetic neuralgia | 180,000 | Adults >=22 years with HZ, Olmsted County MN, 1996-2001 (before zoster vaccine) · https://doi.org/10.4065/82.11.1341 |
| Herpes zoster: Guillain-Barre syndrome within 2 months of HZ | 247 | 315,595 HZ patients, Taiwan national registry, 2003-2005 · https://doi.org/10.1086/655136 |
Excess risk after vaccination (per million doses)
| Guillain-Barre syndrome Shingrix (RZV) | 3 | Medicare beneficiaries >=65 y, US 2017-2020 · doi:10.1001/jamainternmed.2021.6227; PMID 34724025 |
Compiled from study abstracts and FDA/CDC pages, verified 2026-10-09; full table with every source on vaccine safety studies. Data: active_surveillance_results.json, disease_risks.json.
Trials, timing and other data sources
Randomized placebo-controlled trials: serious adverse events
Trials on ClinicalTrials.gov with posted results and a placebo, saline or no-vaccine control arm (14,344 vaccinated vs 14,346 controls), pooled with a random-effects model:
- Any serious adverse event: RR 1.01 (95% CI 0.83–1.25), 3 trials, I² 26% — no significant difference
- Death (any cause, including from the disease itself): RR 0.95 (95% CI 0.80–1.14), 2 trials, I² 5% — no significant difference
Trials included
| Trial | Title | Vaccine: SAE/n | Control: SAE/n |
|---|---|---|---|
| NCT03563183 | A Study to Assess Frailty of Subjects During ZOSTER-006 and ZOSTER-022 | 1,734/13,487 | 1,817/13,489 |
| NCT04091451 | Safety and Immunogenicity Study of GlaxoSmithKline's Herpes Zoster Subunit Vaccine (HZ/su) | 56/714 | 43/712 |
| NCT05219253 | A Study on the Immune Response and Safety of a Vaccine Against Herpes Zoster in Adults Age | 1/143 | 2/145 |
Only blinded, placebo-controlled periods are used (open-label, crossover, booster and extension periods excluded) and vaccine and placebo arms are matched within the same trial part. Risk ratios use participant counts, not person-time: where placebo recipients crossed over to vaccine, the placebo arm is followed for less time, which pushes count-based ratios up. Serious adverse events are sponsor-coded and include events unrelated to vaccination; trials were powered for efficacy, not rare harms; most childhood-vaccine trials use active comparators and therefore do not appear here. Code: analysis/vaccine_trial_meta.py; data: vaccine_trial_meta.json.
When do reported events start? (time to onset)
Days from vaccination to onset in U.S. VAERS reports (0–180 days). A causal reaction usually starts inside a characteristic window; but people also report what happens soon after a shot, so each event is compared with all other reports for this vaccine. The Weibull shape measures bunching (below 1 = most onsets early).
| Event | Reports | Median days | In risk window | Shape (95% CI) vs others | Reading |
|---|---|---|---|---|---|
| Herpes zoster | 4,848 | 4 | 73% (others 52%) | 0.62 (0.61–0.63) vs 0.70 | clusters earlier than other reports |
| Syncope | 686 | 0 | 92% (others 78%) | 0.83 (0.74–1.04) vs 0.70 | spread later than other reports |
| Bell's palsy / facial paralysis | 281 | 5 | 74% (others 52%) | 0.67 (0.62–0.73) vs 0.70 | same timing as other reports |
| Guillain-Barré syndrome | 204 | 9 | 76% (others 52%) | 0.76 (0.69–0.85) vs 0.70 | same timing as other reports |
| Seizure (any) | 194 | 1 | 94% (others 97%) | 0.63 (0.58–0.78) vs 0.70 | same timing as other reports |
| Stroke | 101 | 4 | 63% (others 51%) | 0.59 (0.54–0.70) vs 0.70 | same timing as other reports |
| Anaphylaxis | 96 | 0 | 81% (others 78%) | 0.63 (0.55–1.10) vs 0.70 | same timing as other reports |
| Myocardial infarction | 42 | 1 | 55% (others 51%) | 0.49 (0.43–0.60) vs 0.70 | clusters earlier than other reports |
| Transverse myelitis | 39 | 7 | 67% (others 52%) | 0.57 (0.48–0.74) vs 0.70 | same timing as other reports |
| Venous thromboembolism | 39 | 3 | 92% (others 52%) | 0.93 (0.78–1.21) vs 0.70 | spread later than other reports |
| ADEM / encephalitis | 32 | 7.5 | 72% (others 52%) | 0.69 (0.55–1.06) vs 0.70 | same timing as other reports |
| Myocarditis / pericarditis | 28 | 3 | 79% (others 95%) | 0.69 (0.60–1.07) vs 0.70 | same timing as other reports |
Timing alone cannot establish causation; it can make it more or less plausible. *Fitted on a random sample of 5,000 of these reports. Data: vaers_onset.json.
4. Disease Prevention Context
Lifetime shingles risk is ~30%; incidence rises sharply after 50. Shingrix substantially reduces shingles and PHN in trial and observational data. VAERS counts do not measure vaccine effectiveness.
Zoster-related case literature · Varicella / VZV family page