1. Basic Information
Disease Overview
- Rabies: Viral encephalitis transmitted through bites or scratches from infected mammals (dogs cause the large majority of the >59,000 estimated annual deaths worldwide, mostly in Asia and Africa; bats are the primary vector in the U.S.). Once clinical symptoms appear, rabies is nearly 100% fatal — it is one of the most lethal infectious diseases known, but is also nearly 100% preventable with timely prophylaxis.
Pre- and Post-Exposure Regimens
| Regimen | Who | Schedule |
|---|---|---|
| Pre-exposure prophylaxis (PrEP) | Travelers to high-risk areas, veterinarians, animal handlers, lab workers, spelunkers | 2-dose series (days 0, 7) per 2022 ACIP update, reduced from the older 3-dose series for most people; occupational-risk groups undergo periodic titer checks and booster as needed |
| Post-exposure prophylaxis (PEP), previously unvaccinated | Anyone with a bite/scratch/mucous-membrane exposure to a potentially rabid animal | 4-dose vaccine series (days 0, 3, 7, 14; 5th dose on day 28 if immunocompromised) plus rabies immune globulin (RIG) infiltrated at the wound site |
| PEP, previously vaccinated (PrEP or prior PEP) | Same as above, with documented prior vaccination | 2-dose booster series (days 0, 3); no RIG needed |
Source: CDC ACIP Rabies Recommendations (2022 update); WHO Rabies position paper (2018).
Licensed Products (U.S.)
- Imovax Rabies® (Sanofi) — human diploid cell vaccine (HDCV).
- RabAvert® (GSK) — purified chick embryo cell vaccine (PCECV).
- Rabies immune globulin (HyperRAB, Imogam Rabies-HT) — provides immediate passive antibody at the wound site while active immunity develops from the vaccine series.
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.
Imovax Rabies Sanofi Pasteur · Inactivated
Delivery
Route: Intramuscular (IM)
Form: Lyophilized powder (reconstitute)
Dose volume: 1 mL
Presentation: single-dose vial + diluent
Encapsulation / delivery vehicle
None (no nanoparticle/VLP encapsulation system)
Antigens
| Antigen | Type | Amount / dose |
|---|---|---|
| Rabies virus antigen (β-propiolactone inactivated) Strain: PM-1503-3M · System: MRC-5 human diploid cells | Inactivated virus | ≥2.5 IU |
Adjuvants
None listed on the package insert for this product (common for live attenuated and some inactivated whole-virus vaccines).
Preservatives
- None — Single-dose presentation; label states no preservative.
Excipients & residuals
| Ingredient | Category | Amount | Role |
|---|---|---|---|
| Human albumin | Stabilizer | <100 mg | stabilizer |
| Neomycin sulfate | Residual (antibiotic) | <150 mcg | residual |
| Phenol red indicator | Other | 20 mcg | indicator |
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 / hypersensitivity | 0–1 days |
Possible
Evidence: Moderate |
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. |
| 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). |
| Neurologic events (historical neural-tissue vaccines) | 0–42 days |
Unlikely
Evidence: 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. |
| 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). |
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.
2. Pre-Licensure Clinical Trial Data
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.
Because deliberately exposing trial participants to rabies would be unethical, efficacy cannot be studied via placebo-controlled challenge trials in humans. Evidence instead comes from immunogenicity trials, and from the extensive real-world record of PEP outcomes.
| Metric | Data | Evidence Strength |
|---|---|---|
| Seroconversion (adequate neutralizing antibody titer) | >95–99% after complete PrEP or PEP series in immunogenicity trials | Strong |
| 2-dose vs. 3-dose PrEP non-inferiority (2022 ACIP change) | Multiple immunogenicity studies supported the shift to a 2-dose primary PrEP series for most people | Strong |
| Direct PEP effectiveness | No RCTs (unethical); real-world record across millions of PEP courses shows treatment failures are exceedingly rare and almost always tied to delayed/incomplete PEP or omission of RIG | Strong |
Key Limitations
- No placebo-controlled human efficacy trial: Ethically impossible; effectiveness is inferred from immunogenicity and the real-world PEP failure-case literature.
- PEP failures, when they occur, are almost always attributable to protocol deviations (delayed treatment initiation, RIG omitted or not infiltrated at the wound, incomplete dose series) rather than vaccine failure per se.
3. Post-Licensure Safety Data
Post-Licensure Safety Monitoring
| Metric | Finding |
|---|---|
| Serum sickness-like reactions with booster doses | Reported in up to ~6% of people receiving multiple HDCV boosters, thought to be an immune-complex reaction to the human albumin stabilizer; more common with older vaccine lots and repeat boosting than with primary series |
| Historical GBS-like reactions with older nerve-tissue vaccines | Older Semple-type (nerve-tissue-derived) rabies vaccines, still used in some countries decades ago, carried a much higher neurologic complication rate; modern cell-culture vaccines (HDCV, PCECV) do not share this risk profile |
| VAERS review, modern cell-culture vaccines | Dominated by injection site and mild systemic reactions; no unusual serious safety signal identified |
⚠ Critical Caveat
Rabies is essentially always fatal once symptomatic, and PEP is highly time-sensitive. Any potential rabies exposure warrants urgent medical evaluation regardless of prior vaccination status — do not wait for confirmatory animal testing where risk is significant.
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 ZIP CAPTCHA downloads use this site’s vaers_pipeline.py; FAERS is bulk quarterly ZIP via SurVigilance (not product search).
VAERS (United States)
Canada Vigilance (Canada)
JADER (PMDA, Japan)
EudraVigilance (EU)
5,183
individual cases · adrreports.eu DAP export (up to 28/06/2026)
Reaction SOC breakdown not included in this workbook export.
SurVigilance: VigiAccess · Lareb · DAEN · DMA · Medsafe
VigiAccess (WHO)
Lareb (Netherlands)
DAEN (Australia)
No DAEN (Australia) data yet — run python scrape_survigilance_one.py daen <vaccine-id> or python survigilance_pipeline.py --system daen (SurVigilance + direct scrapers: GitHub).
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)
4. Documented Adverse Events — Evidence of Association
Rank-aggregated VAERS signal detection (rankv)
No pairs mapping to this product family appear in the rank-aggregated common-signal set from rankv (intersection of GPS, PRR, ROR, and BCPNN signals). That does not mean absence of all VAERS reports — only that no pair met the four-method consensus filter in the published pipeline.
- 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.
▶ Strong Evidence of Causal Association
- Injection site pain, redness, swelling: Common, ~30–74% depending on vaccine/regimen. Self-limited. Strong
- Headache, dizziness, myalgia, nausea: ~5–40%. Self-limited. Strong
- Serum sickness-like reaction (booster doses): Up to ~6% with repeat HDCV boosting; immune-complex mediated, self-limited but can be uncomfortable (urticaria, arthralgia, fever, 2–21 days after boost). Strong
- Anaphylaxis: Rare, consistent with other injectable cell-culture vaccines. Strong
▶ Published Evidence Does Not Support a Causal Association
- Guillain-Barré syndrome, modern cell-culture vaccines: The elevated GBS-like signal was specific to older nerve-tissue-derived (Semple-type) vaccines; no consistent signal has been found with HDCV/PCECV. No Association (modern vaccines)
5. Disease Prevention Benefits
Effectiveness in Practice
| Metric | Data |
|---|---|
| PEP effectiveness when protocol followed correctly and promptly | Essentially 100%; documented human rabies deaths after correctly and promptly administered PEP (vaccine + RIG) are exceedingly rare case reports |
| Global mortality burden | ~59,000 deaths/year worldwide (WHO estimate), >95% in Asia and Africa, overwhelmingly linked to dog bites in areas with limited PEP access |
| U.S. burden | Typically 1–3 human deaths/year, almost always from unrecognized bat exposure without PEP; PEP is administered to tens of thousands of people annually in the U.S. as a precaution |
Source: WHO Rabies Fact Sheet; CDC Rabies Surveillance Summaries.
6. Evidence Summary
Modern cell-culture rabies vaccines, combined with rabies immune globulin for unvaccinated exposures, are considered essentially 100% effective at preventing a disease that is otherwise almost universally fatal once symptomatic. The main real-world "failures" reflect delayed or incomplete treatment rather than vaccine performance. Adverse events are generally mild, with serum sickness-like reactions to repeat boosters being the most distinctive, well-characterized reaction pattern.
| Domain | Evidence Grade | Key Finding |
|---|---|---|
| PEP effectiveness (protocol followed) | Strong | Essentially 100% when given promptly and completely |
| PrEP immunogenicity | Strong | >95–99% seroconversion |
| Serum sickness-like reactions (repeat boosters) | Strong | Up to ~6% with repeat HDCV boosting |
| GBS (modern vaccines) | No Association | Signal specific to older nerve-tissue vaccines, not HDCV/PCECV |
7. International Surveillance & Global Data
Quick links to public pharmacovigilance databases and trial registries relevant to Rabies Vaccine. Reporting counts do not establish causality.
8. Curated Adverse Event Literature
Curated peer-reviewed literature linking specific adverse events to Rabies Vaccine. Each entry is a case report, case series, or related safety publication identified via PubMed. Expand Search PubMed for additional literature below to run custom queries.
9. Key References
- WHO. Rabies vaccines: WHO position paper. Wkly Epidemiol Rec. 2018;93(16):201–219.
- CDC. Use of a Modified Preexposure Prophylaxis Vaccination Schedule for Rabies. MMWR. 2022;71(18):619–627.
- CDC. Rabies. CDC Yellow Book, Travelers’ Health. cdc.gov/yellowbook
- Manning SE, et al. Human Rabies Prevention — ACIP Recommendations. MMWR Recomm Rep. 2008;57(RR-3):1–28.
- WHO. Rabies Fact Sheet. who.int