1. Basic Information
Disease Overview
- Japanese Encephalitis (JE): Mosquito-borne flavivirus (Culex species vectors, amplified in pigs and wading birds), endemic across most of Asia and parts of the Western Pacific. Most infections are asymptomatic (<1% develop encephalitis), but among those with symptomatic encephalitis, case-fatality is 20–30%, and 30–50% of survivors have long-term neuropsychiatric sequelae. It is the leading vaccine-preventable cause of encephalitis in Asia.
Recommended Use
| Population | Recommendation |
|---|---|
| Travelers ≥1 month in endemic rural areas during transmission season | 2-dose primary series, days 0 and 28 (accelerated 1-week schedule available for adults 18–65) |
| Shorter-term travelers with high-risk activities | Outdoor/rural/agricultural exposure, or uncertain itinerary, may still warrant vaccination per individualized risk assessment |
| Booster | Single booster at ≥1 year if ongoing/future JE exposure risk continues |
| Age range (U.S. product) | Licensed for age ≥2 months |
Source: CDC Yellow Book; ACIP JE vaccine recommendations (2019 update).
Licensed Products
- IXIARO® (Valneva) — inactivated, Vero-cell-derived. Licensed in the U.S. since 2009 (adults) and 2013 (children ≥2 months). Replaced the older mouse-brain-derived JE-VAX, discontinued in the U.S. in 2011.
- SA14-14-2 (live-attenuated) — used in China, India, and other endemic-country national immunization programs (e.g., part of China's EPI schedule); not licensed in the U.S.
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.
Ixiaro Valneva Austria GmbH · Inactivated
Delivery
Route: Intramuscular (IM)
Form: Suspension for injection
Dose volume: 0.5 mL
Presentation: single-dose prefilled syringe
Encapsulation / delivery vehicle
None (no nanoparticle/VLP encapsulation system)
Antigens
| Antigen | Type | Amount / dose |
|---|---|---|
| Japanese encephalitis virus proteins, purified inactivated | Inactivated virus | ≈6 mcg |
Adjuvants
- Aluminum hydroxide — 250 mcg aluminum hydroxide
Preservatives
- None — No preservatives, stabilizers, or antibiotics added.
Excipients & residuals
| Ingredient | Category | Amount | Role |
|---|---|---|---|
| Phosphate-buffered saline | Buffer | vehicle | vehicle |
| Formaldehyde | Residual (inactivating agent) | ≤200 ppm residual | residual |
| Bovine serum albumin | Residual (manufacturing) | ≤100 ng/mL residual | residual |
| Host cell DNA | Residual (manufacturing) | ≤200 pg/mL residual | residual |
| Sodium metabisulphite | Residual (manufacturing) | ≤200 ppm residual | process residual |
| Protamine sulfate | Residual (manufacturing) | ≤1 mcg/mL residual | process residual |
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). |
| 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). |
| Neurologic events (encephalitis-like) | 0–42 days |
Unclassifiable
Evidence: Very Low |
Vaccine-strain encephalitis / encephalomyelitis (hypothetical · live_replication) Live viral vaccines can rarely cause CNS infection or demyelinating encephalomyelitis via direct viral invasion or post-infectious immune attack. 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.
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.
IXIARO's licensure was supported by immunogenicity (non-inferiority to the older JE-VAX) and safety trials in adults and children across the U.S., Europe, and endemic Asian countries.
| Metric | Data | Evidence Strength |
|---|---|---|
| Seroconversion after 2-dose primary series | >95% across adult and pediatric immunogenicity trials | Strong |
| Pediatric safety database | ~JE-endemic-country pediatric trials totaling several thousand children supported the 2013 pediatric licensure | Moderate |
| Direct clinical efficacy (disease endpoint) trial | Not conducted (immunogenicity-based licensure, standard for JE vaccines given low absolute incidence in any single trial population) | Limited |
Key Limitations
- Immunogenicity-based licensure: Like several travel vaccines, IXIARO's approval relies on antibody response as a correlate of protection rather than a direct disease-endpoint efficacy trial, since JE incidence in any feasible trial population/travel cohort is too low to power such a study.
- Long-term durability beyond the 1-year booster point is less well characterized than for some routine childhood vaccines, given the vaccine's relatively recent (2009) introduction.
3. Post-Licensure Safety Data
Post-Licensure Safety Monitoring
A CDC/FDA review of VAERS reports from IXIARO's first several years on the U.S. market (2013 review covering 2009–2012) did not identify an unusual or unexpected adverse event pattern compared to other inactivated travel vaccines.
| Metric | Finding |
|---|---|
| VAERS review (2009–2012 U.S. data) | No unusual safety signal identified; reports dominated by injection site and mild systemic reactions |
| Comparison to older JE-VAX | IXIARO has a substantially improved reactogenicity and allergy profile compared to the discontinued mouse-brain-derived JE-VAX, which had higher rates of delayed urticarial/allergic reactions |
⚠ Critical Caveat
VAERS data represent unverified reports temporally associated with vaccination and cannot establish causality or incidence rates on their own.
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)
1,168
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/tenderness: Common, ~30–60%. Self-limited. Strong
- Headache, myalgia, fatigue: ~20–30%. Self-limited. Strong
- Anaphylaxis: Rare, consistent with other inactivated injectable vaccines. Strong
▶ Moderate or Preliminary Evidence
- Delayed urticaria (older JE-VAX, historical): Documented with the discontinued mouse-brain-derived vaccine; not seen at meaningfully elevated rates with the current Vero-cell IXIARO product. Limited (legacy vaccine)
5. Disease Prevention Benefits
Program Impact (Endemic-Country Live-Vaccine Programs)
| Country/Program | Outcome |
|---|---|
| China (SA14-14-2, national EPI) | Routine childhood JE vaccination since the 1980s–2000s associated with major declines in reported pediatric JE incidence |
| India (endemic districts) | Campaign and routine SA14-14-2 vaccination in high-burden districts associated with sharp reductions in encephalitis hospitalizations attributable to JE |
| Traveler protection (IXIARO) | No large-scale traveler effectiveness studies exist due to the rarity of JE in short-term travelers, but seroprotection correlates strongly predict clinical protection based on decades of field experience with JE vaccines generally |
Source: WHO JE position paper (2015); national surveillance summaries (China CDC, India NVBDCP).
6. Evidence Summary
IXIARO provides strong, well-documented immunogenicity against a disease with high case-fatality and disability among the small fraction of infections that become symptomatic. Its safety profile is favorable and represents a substantial improvement over the discontinued mouse-brain-derived predecessor vaccine. The main evidence gap, shared by most travel vaccines, is the absence of a direct disease-endpoint efficacy trial.
| Domain | Evidence Grade | Key Finding |
|---|---|---|
| Immunogenicity | Strong | >95% seroconversion after 2-dose series |
| Reactogenicity | Strong | Mostly mild, self-limited local/systemic reactions |
| Direct efficacy (disease endpoint) | Limited | Licensure based on immunogenicity, not disease-endpoint RCT |
| Serious safety signal | No Association | No unusual pattern in post-licensure VAERS review |
7. International Surveillance & Global Data
Quick links to public pharmacovigilance databases and trial registries relevant to Japanese Encephalitis Vaccine. Reporting counts do not establish causality.
8. Curated Adverse Event Literature
Curated peer-reviewed literature linking specific adverse events to Japanese Encephalitis 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. Japanese encephalitis vaccines: WHO position paper. Wkly Epidemiol Rec. 2015;90(9):69–87.
- CDC. Japanese Encephalitis. CDC Yellow Book, Travelers’ Health. cdc.gov/yellowbook
- Hills SL, et al. Japanese Encephalitis Vaccine: Recommendations of ACIP. MMWR Recomm Rep. 2019;68(2):1–33.
- Schuller E, et al. Long-term immunogenicity of the new Vero cell-derived, inactivated Japanese encephalitis virus vaccine. Vaccine. 2008;26(37):4382–4386.