Name: Influenza Vaccine
Brand: Fluzone
SKU: influenza

1. Basic Information

Disease Protected Against

Seasonal influenza is a respiratory viral infection causing annual epidemics. Disease burden varies substantially by season, circulating strains, and population immunity. In the U.S., influenza causes an estimated 9–41 million illnesses, 140,000–710,000 hospitalizations, and 12,000–52,000 deaths annually (2010–2023 average). Children <5 years (especially <2) and children with underlying medical conditions are at highest risk for severe complications. The 2009 H1N1 pandemic was a reminder of pandemic influenza risk, though seasonal and pandemic vaccines are distinct products.

CDC Schedule (U.S., 2025)

Population	Recommendation
All persons ≥6 months without contraindication	Annual influenza vaccination (universal recommendation since 2010)
Children 6 months–8 years (first-time vaccination)	2 doses, ≥4 weeks apart (priming series)
Children 6 months–8 years (previously vaccinated)	1 dose annually
Pregnant women	IIV recommended in any trimester; LAIV contraindicated

Source: CDC ACIP. Multiple products available: egg-based IIV, cell-culture-based IIV (Flucelvax), recombinant HA vaccine (Flublok), and LAIV (FluMist, intranasal). For the 2024–25 season and beyond, all U.S. influenza vaccines are trivalent (H1N1, H3N2, and one B lineage, following the global disappearance of the Yamagata B lineage).

Notable Historical Safety Events

1976 Swine flu vaccine and GBS: The 1976 H1N1 swine flu vaccine was associated with an estimated ~1 excess case of Guillain-Barré Syndrome per 100,000 doses. This vaccine was withdrawn. The 1976 GBS association is the most significant safety event in influenza vaccine history and is the reference point against which all subsequent influenza vaccine GBS surveillance is compared.
2009 H1N1 pandemic vaccines (monovalent): Some European countries identified a small increased risk of narcolepsy following Pandemrix (AS03-adjuvanted H1N1 vaccine used in Europe; not used in the U.S.), estimated at ~3–7 excess cases per 100,000 vaccinated children. The mechanism is thought to involve molecular mimicry between the H1N1 nucleoprotein and the hypocretin receptor in genetically susceptible individuals (HLA-DQB1*0602). This adjuvant and formulation were not used in U.S. seasonal vaccines.
2014–2015 LAIV reduced effectiveness: LAIV (FluMist) showed low effectiveness against H1N1pdm09 during the 2013–14 and 2015–16 seasons. ACIP recommended against LAIV use in 2016–17 and 2017–18; LAIV was reformulated and re-recommended starting 2018–19.

Documented Adverse Events (HRSA VICP)

The following adverse events are documented by the HRSA Vaccine Injury Compensation Program (VICP) as having a temporal relationship to this vaccine. These are not necessarily confirmed causal relationships, but rather conditions for which claims have been compensated or are presumed caused by the vaccine.

WHO Causality Assessment Methodology

The World Health Organization's Global Advisory Committee on Vaccine Safety (GACVS) uses a 4-level causality classification:

Consistent: Epidemiological studies demonstrate a statistically significant association with temporal specificity and biological plausibility. Replicated across independent populations and study designs.
Indeterminate: Evidence exists but is insufficient to confirm or rule out causality. May be limited by sample size, confounding, or inconsistency across studies.
Inconsistent: Studies have not demonstrated a consistent or convincing association. Evidence against causality outweighs evidence for it.
Unclassifiable: Insufficient data to reach any conclusion. Requires further evidence.

Source: WHO Global Advisory Committee on Vaccine Safety (GACVS), 2021–2025 causality review cycles. See also Institute of Medicine (IOM) Adverse Effects of Vaccines: Evidence and Causality (2012) for pre-COVID vaccine assessments.

Condition	Time Window	Causality Level	HRSA Description
Anaphylaxis	0-1 days	Consistent WHO Determination (2021, 2023): Consistent for all COVID-19 vaccines. Rate: ~2–5 per million doses. Temporal specificity (onset within minutes, consistent with IgE-mediated). Plausible biological mechanism: immediate hypersensitivity to vaccine excipients (PEG for mRNA, polysorbate for adenoviral). Verified via passive surveillance convergence across multiple national systems (VAERS, EudraVigilance, MHRA Yellow Card, TGA DAEN). Biological Mechanism: Not thought to be spike protein mediated; likely polyethylene glycol (PEG) in mRNA vaccines triggers IgE-mediated mast cell degranulation Clinical Evidence: (Kuder et al., 2021); Mechanism: (Risma et al., 2021) Spike Protein Evidence: Not tested	Anaphylaxis occurring within 4 hours following vaccination
Guillain-Barré Syndrome (GBS)	0-42 days	Consistent WHO Determination (2021, 2023, 2024): Consistent for adenovirus-vectored, indeterminate for mRNA. Self-controlled risk-interval designs show 2–4 × baseline within 42 days. Molecular mimicry between vaccine-induced antibodies and peripheral nerve gangliosides proposed. For mRNA: Conflicting evidence, potential small signal requires further study. Biological Mechanism: Molecular mimicry between spike protein and peripheral nerve antigens Clinical Evidence: (Abara et al., 2023; Hanson et al., 2022; Yu et al., 2023) Spike Protein Evidence: Possible negative results: mice stimulated with SARS-CoV-2 spike protein did not develop autoimmunity (Scherlinger et al., 2023)	GBS occurring within 3-42 days following vaccination (primarily 1976 swine flu vaccine; modern vaccines signal uncertain)
Syncope (Fainting)	0-1 days	Indeterminate WHO / IOM Causality Assessment: Evidence reviewed; causal association cannot be confirmed or excluded at current evidence level. Requires further epidemiological and mechanistic investigation. See HRSA VICP Table for program-specific determination. Biological Mechanism: Multiple plausible biological mechanisms under investigation. Brighton Collaboration AESI monitoring ongoing. Clinical Evidence: See HRSA VICP/CICP program documentation for current determination. Spike Protein Evidence: Evidence reviewed; consult Brighton Collaboration list for mechanistic assessment status.	Syncope occurring within a few minutes to 2 hours after vaccination

Important Notes

HRSA VICP: Conditions listed are documented by HRSA as having temporal relationship to vaccination. Compensation does not imply causation.
Temporal Association: These conditions occurred after vaccination within the specified time window, but other factors may have contributed.
Rarity: Most adverse events are extremely rare. Serious adverse events from vaccines occur in roughly 1-2 per million doses.
Biological Plausibility: Mechanistic evidence is under review and will be integrated in Q3 2026.
Benefit-Risk: This page documents documented injuries. See disease burden pages for context on prevented diseases.

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.

Inactivated Intramuscular (IM) Preservative: Thimerosal Thimerosal Egg protein Formaldehyde

Fluzone Quadrivalent Sanofi Pasteur · Inactivated

Delivery

Route: Intramuscular (IM)

Form: Suspension for injection

Dose volume: 0.25 mL or 0.5 mL (age-dependent)

Presentation: single-dose prefilled syringe or multi-dose vial

Encapsulation / delivery vehicle

None (no nanoparticle/VLP encapsulation system)

Antigens

Antigen	Type	Amount / dose
Influenza A (H1N1) hemagglutinin	Inactivated virus	15 mcg HA / 0.5 mL (strain changes seasonally)
Influenza A (H3N2) hemagglutinin	Inactivated virus	15 mcg HA / 0.5 mL
Influenza B (Victoria lineage) hemagglutinin	Inactivated virus	15 mcg HA / 0.5 mL
Influenza B (Yamagata lineage) hemagglutinin	Inactivated virus	15 mcg HA / 0.5 mL

Adjuvants

None listed on the package insert for this product (common for live attenuated and some inactivated whole-virus vaccines).

Preservatives

Thimerosal — 25 mcg mercury per 0.5 mL from multi-dose vial only
Single-dose prefilled syringes: no thimerosal. Multi-dose vials: thimerosal as preservative.

Excipients & residuals

Ingredient	Category	Amount	Role
Egg protein (ovalbumin)	Residual (culture)	residual from egg-based manufacture	residual
Formaldehyde	Residual (inactivating agent)	residual	inactivation residual
Octylphenol ethoxylate (Triton X-100)	Surfactant	residual	splitting agent residual
Sodium phosphate-buffered isotonic sodium chloride	Buffer	q.s.	vehicle

Always check vial type: preservative status differs between single-dose and multi-dose presentations.

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 HRSA table	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.
Guillain-Barré Syndrome (GBS) HRSA table	0–42 days	Possible Evidence: Moderate	Molecular mimicry → Guillain-Barré syndrome (primary · molecular_mimicry) Vaccine- or infection-triggered immune responses cross-react with peripheral-nerve gangliosides or myelin components, producing demyelinating or axonal polyneuropathy.
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).
Bell's palsy	0–30 days	Unlikely Evidence: Low	Facial nerve inflammation (Bell's palsy-type) (hypothetical · innate_inflammation) Transient inflammatory neuropathy of CN VII has been hypothesized after some vaccines; evidence of causal association is often weak or product-specific. 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)

The table below reproduces ICAN’s No Placebo Table rows for U.S. childhood-schedule products relevant to this page — including the control/comparator used in FDA licensing trials (not always saline placebo). OSMF presents this for transparency; it is not an endorsement of ICAN interpretations.

Vaccine	Brand	Manufacturer	Doses (schedule)	Ages injected	Control / comparator	Placebo	Safety review window
Flu	Various	Various	19	6M 7M Yearly	Flu shots change annually without any clinical trial	No	Flu shots change annually without any clinical trial

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 influenza vaccines are reformulated annually, the typical pre-licensure paradigm does not apply in the same way as for other vaccines. New products undergo initial licensure with full clinical trials; subsequent annual strain changes are licensed based on manufacturing process consistency and immunogenicity data in smaller bridging studies (per FDA guidance).

Product Type	Initial Licensure Database	Seasonal Strain Changes
Egg-based IIV	Licensure dating to 1940s (original products); modern products: ~3,000–5,000 per age group	Bridging immunogenicity studies; ~300–500 participants per strain update
LAIV (FluMist)	~28,000 children across pivotal trials (originally licensed 2003)	Bridging studies; extensive post-licensure data
Cell-culture IIV (Flucelvax)	~7,000 in pivotal trials (licensed 2012)	Bridging studies

Most Common Adverse Reactions (Seasonal IIV)

Reaction	IIV (children)	LAIV (children)
Injection site pain/tenderness	~40–65%	N/A (intranasal)
Injection site redness/swelling	~10–20%	N/A
Fever	~5–15% (children <5)	~5–10%
Runny nose/nasal congestion	~10–20%	~40–60% (expected; administered intranasally)
Headache	~10–20%	~15–25%
Fatigue/malaise	~15–25%	~10–20%
Wheezing (LAIV, children <2 with asthma history)	N/A	Increased risk; contraindicated in children <2 and those with asthma/wheezing

Key Limitations

Variable effectiveness: Influenza vaccine effectiveness ranges from ~10–60% depending on season, strain match, age, and prior vaccination. This is fundamentally different from other childhood vaccines with >85% effectiveness. The need for annual reformulation is a unique limitation.
Prior vaccination effects: Repeated annual vaccination may reduce vaccine effectiveness in some seasons (antigenic distance hypothesis), though data are inconsistent. This is actively studied.
Annual safety data limited: Strain-change bridging studies are small (hundreds of participants). Most safety evidence is post-licensure.
Febrile seizure risk with PCV13 combination: In the 2010–11 season, co-administration of IIV and PCV13 was associated with an increased febrile seizure risk (~1 per 2,000 doses). This was season- and product-specific. (This is also noted on the PCV page.)

3. Post-Licensure Safety Data

VSD Findings

Guillain-Barré Syndrome (GBS): The VSD and other surveillance systems have estimated the GBS risk following seasonal influenza vaccine at ~1–2 excess cases per million doses, substantially lower than the 1976 swine flu vaccine risk (~1 per 100,000). Some seasons show no statistically significant increase. IOM (2012) concluded evidence favors acceptance of a causal relationship for influenza vaccine and GBS (based primarily on the 1976 vaccine data; evidence for seasonal vaccines is less robust).
Febrile seizures (IIV + PCV13, 2010–11): Signal identified and resolved. See PCV page.
No increase in adverse pregnancy outcomes with IIV during pregnancy. Extensive VSD and registry data are consistent.
Anaphylaxis: ~1–2 per million doses.

⚠ Critical Caveat

VAERS data represent unverified reports. A report to VAERS does not mean the vaccine caused the event. Because influenza vaccine is given annually to very large populations, VAERS report volumes are high relative to other vaccines, reflecting exposure volume rather than elevated risk.

VAERS Reporting Data — Halma & Varon (2025), DARE-SAFE

The DARE-SAFE paper (Halma & Varon, Pharmacoepidemiology 2025, CC BY 4.0) analyzed VAERS reports for vaccines administered in the United States from 2006–2022. The following data are extracted from Table 1 of that paper for this vaccine (Seasonal influenza (all formulations combined); ~2.4 billion doses is far larger than any other denominator):

Metric	Value
U.S. doses administered (2006–2022)	2,407,000,000
Total VAERS AE reports	149,512
AE reporting rate (per 100,000 doses)	6.21
Total death reports	650
Death reporting rate (per 100,000 doses)	0.0270
AE-to-Death ratio	230:1

Source: Halma, M.; Varon, J. DARE-SAFE. Pharmacoepidemiology. 2025. DOI: 10.3390/pharma4020007. CC BY 4.0. Data from Table 1.

📚 Important Interpretive Caveats (from the paper itself)

Reporting rate ≠ incidence rate. VAERS is a passive, unverified system. A report means someone submitted a claim of temporal association, not a confirmed causal event. The paper is explicit that causality cannot be inferred from these numbers alone.
Reporting behavior is not uniform. More serious, unusual, or media-salient events are reported at much higher rates than mild ones. Products receiving more public, media, legal, and clinical attention (particularly COVID-19 vaccines, which also benefited from V-safe active-surveillance prompts and CICP compensation pathways) generate more reports per dose regardless of true risk.
Age and comorbidity confounding is not adjusted. COVID-19 vaccines were disproportionately administered to elderly and comorbid populations (nursing homes, 65+, high-risk groups in early 2021) with much higher background all-cause mortality than the general child/working-age population. Some fraction of temporally-associated deaths would occur regardless of vaccination, and the paper does not perform a background-rate comparison.
Stimulated reporting is a known, documented phenomenon. Media coverage, plaintiff attorney solicitation, and advocacy campaigns — all independently inflate VAERS reporting propensity. The paper cites this literature but does not correct for it.
Small-denominator rows are unreliable. Rates computed from small denominators (e.g., monovalent measles, DT, mumps, rubella) have enormous statistical uncertainty and should not be compared to vaccines with hundreds of millions of administered doses without noting the wide confidence intervals.

Source: Halma, M.; Varon, J. DARE-SAFE: Denominator-Adjusted Rate Estimates of Substance Adverse Events Frequency Evaluation in Pharmaceuticals and Vaccines. Pharmacoepidemiology. 2025, 4, 7. DOI: 10.3390/pharma4020007. CC BY 4.0.

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)

No matching vaccine cases in the current EudraVigilance DAP export.

SurVigilance: VigiAccess · Lareb · DAEN · DMA · Medsafe

VigiAccess (WHO)

Lareb (Netherlands)

DAEN (Australia)

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)

VAERS (U.S., 2006–2024): 461,098 symptom mentions (3.83/100k doses). Largest share: Other / Unclassified (18%), General / Systemic (non-local) (17%), Injection-site / Local reaction (14%). Canada Vigilance (CV Online extract): 13,174 reaction mentions in 2,244 unique reports (59.7% serious (1,340 of 2,244 reports)). Largest share: General / Systemic (non-local) (14%), Neurological (11%), Respiratory (11%). JADER (PMDA public CSV extract): 5,903 reaction mentions in 3,723 unique reports (10.6% serious (395 of 3,723 reports)). Largest share: Other / Unclassified (21%), Neurological (21%), General / Systemic (non-local) (16%). VigiAccess (WHO): 1,018,882 reaction-term mentions · search: influenza. Largest share: Injection-site / Local reaction (18%), General / Systemic (non-local) (18%), Other / Unclassified (13%). Lareb (Netherlands): 18,531 reaction-term mentions · search: Influenza vaccine. Largest share: Other / Unclassified (19%), General / Systemic (non-local) (13%), Musculoskeletal (12%). DAEN (Australia): 82,948 reaction-term mentions · search: influenza. Largest share: General / Systemic (non-local) (18%), Other / Unclassified (14%), Neurological (13%). Medsafe (New Zealand): 46 reaction-term mentions · search: influenza. Largest share: Gastrointestinal (30%), General / Systemic (non-local) (22%), Neurological (15%). Cross-database note: All systems are passive and unverified; reporting rates are not directly comparable across countries (different populations, reporting incentives, and lack of dose denominators for Canada/Japan/EU). top VAERS: Other / Unclassified; top Canada Vigilance: General / Systemic (non-local); top JADER: Other / Unclassified. SurVigilance note: VigiAccess, Lareb, DAEN, DMA, and Medsafe counts are live-scraped MedDRA PT mention totals (not deduplicated individual cases). Data via SurVigilance (GPL-3.0; pip install SurVigilance). Category assignment uses keyword matching on reported reaction terms — approximate and exploratory. Neither database establishes causality.

Compare AE patterns across all vaccines →

Pharmacovigilance Lot Signal Detection — Hypothesis-Generating Only

Multi-system context below. VAERS (U.S.) supports lot-level volume z-scores and seriousness flags by product and lot (2006–2024). Each lot links to a summary with report count, seriousness %, adverse-event pie chart, U.S. state map, and timeline. A signal flag means a statistical threshold was exceeded — not that a lot is unsafe. Full dashboard →

VAERS flags: VOL high report volume (z ≥ 3) · BURST clustered in <90 days · SER serious reports >50%. Lot numbers are voluntary/incomplete in VAERS. Location data is U.S. state only (no postal codes in the public extract).

VAERS (United States) — all lots by product

72,151 reports with usable lot across 6,345 lots · 1,630 flagged

Loading lot tables…

Other Pharmacovigilance Systems

Lot-level analysis is only possible where reporters supply batch/lot numbers in the public extract. Canada Vigilance, JADER (PMDA, Japan), and most other national systems publish product-level spontaneous reports without lot fields.

Canada Vigilance (Health Canada)

2,244 unique reports · 13,174 reaction mentions · 59.7% serious (1,340 of 2,244 reports). Top categories: General / Systemic (non-local) (14%), Neurological (11%), Respiratory (11%).

Canada Vigilance spontaneous reports are unverified temporal associations. The public CV Online data extract does not include lot or batch numbers, so lot-level signal detection is not possible for this system — only product-level reaction patterns are shown here. No Canadian dose denominators are available. Extract 2026-03-31.

Search Canada Vigilance →

JADER (PMDA, Japan)

3,723 unique reports · 5,903 reaction mentions · 10.6% serious (395 of 3,723 reports). Top categories: Other / Unclassified (21%), Neurological (21%), General / Systemic (non-local) (16%).

JADER (Japanese Adverse Drug Event Report database) spontaneous reports are unverified temporal associations; PMDA has not assessed causality per case. The public CSV extract does not include lot or batch numbers, so lot-level signal detection is not possible — only product-level reaction patterns are shown here. Reaction terms in source data use MedDRA/J Preferred Terms. JADER CSV extract pmdacasereport202606 (2026-06). JADER reference (PDF)

Search JADER / PMDA adverse reactions →

No EudraVigilance (EU) summary is mapped for this page.

VigiAccess (WHO)

1,018,882 MedDRA PT mentions · search: influenza. Top categories: Injection-site / Local reaction (18%), General / Systemic (non-local) (18%), Other / Unclassified (13%).

Live-scraped public portal data via SurVigilance (GPL-3.0). Counts are reaction-term mentions, not deduplicated individual cases. No lot/batch field.

Search VigiAccess (WHO) →

Lareb (Netherlands)

18,531 MedDRA PT mentions · search: Influenza vaccine. Top categories: Other / Unclassified (19%), General / Systemic (non-local) (13%), Musculoskeletal (12%).

Live-scraped public portal data via SurVigilance (GPL-3.0). Counts are reaction-term mentions, not deduplicated individual cases. No lot/batch field.

Search Lareb (Netherlands) →

DAEN (Australia)

82,948 MedDRA PT mentions · search: influenza. Top categories: General / Systemic (non-local) (18%), Other / Unclassified (14%), Neurological (13%).

Live-scraped public portal data via SurVigilance (GPL-3.0). Counts are reaction-term mentions, not deduplicated individual cases. No lot/batch field.

Search DAEN (Australia) →

System	Region	Lot data
VAERS	United States	Lot data
Canada Vigilance	Canada	No public lot field
JADER (PMDA, Japan)	Japan	No public lot field
Lareb (Netherlands)	Netherlands	No public lot field
EudraVigilance	European Union	No public lot field
VigiAccess (WHO)	Global	No public lot field
Yellow Card (UK)	United Kingdom	No public lot field
DAEN (Australia)	Australia	No public lot field

All global data sources → · Data schemas →

Active Pharmacovigilance (Defined-Population Surveillance)

Curated findings for Influenza vaccines from active systems (not VAERS). Page inventory last reviewed: 2026-07-10.

ⓘ Active vs. passive — why this pane is separate

The VAERS / multi-system charts above are passive surveillance: spontaneous, unverified reports without a fixed denominator. Active surveillance starts from a defined, enumerated population (EHR/claims or structured post-vaccination surveys), applies pre-specified statistical tests, and asks whether an outcome occurs more often than expected in a risk window versus a comparison window or group. These are not two flavors of the same evidence — active findings are the harder tier that can confirm, refute, or leave under investigation a signal first hinted in passive data. Do not add VAERS report counts to active incidence rates.

○ No signal detected ◐ Signal under investigation ◑ Investigated — not confirmed ● Signal confirmed (true association) – Not currently under active surveillance

CDC Vaccine Safety Datalink (VSD)

Outcome: Guillain-Barré syndrome (GBS) and other pre-specified outcomes

Tier 2 ○ No signal detected

Seasonal influenza vaccines are monitored each year in VSD RCA. Modern seasonal formulations have not reproduced the clear GBS risk of the 1976 swine influenza program at comparable magnitude; any residual GBS association, if present, is estimated to be very small and is reassessed seasonally when signals appear.

Population

VSD seasonal influenza vaccinees (age groups vary by season)

Risk interval

Typically ~1–42 days post-vaccination for GBS analyses

Comparison

Control intervals / background rates

Evaluation period

Annual RCA each influenza season; historical 1976 swine-flu program informs baseline concern

Method

Rapid Cycle Analysis (seasonal) and historical epidemiologic studies

Related passive AE category on this page: Neurological (see multi-system charts above — not additive with active rates).

Sources: CDC VSD · AusVaxSafety — influenza safety data

Record last reviewed: 2026-07-10

AusVaxSafety (Australia)

Outcome: Short-term AEFI / medical attendance after influenza vaccination

Tier 1 ○ No signal detected

AusVaxSafety publishes seasonal influenza vaccine safety data from active surveys. Profiles are generally consistent with expected mild reactogenicity; check the current season page for brand-specific rates.

Population

Australian influenza vaccinees in AusVaxSafety sentinel programs

Risk interval

Days 0–3 (primary survey)

Comparison

System signal thresholds

Evaluation period

Seasonal; public pages updated during flu campaigns

Method

Active post-vaccination survey surveillance

Sources: AusVaxSafety vaccine safety data hub

Record last reviewed: 2026-07-10

Update cadence: Tier 1: check AusVaxSafety monthly when public pages update. Tier 2/3: quarterly review around ACIP meetings and PubMed/MMWR; set lastReviewed per record. Source tiers: Tier 1 = public near-real-time dashboards (e.g. AusVaxSafety); Tier 2 = VSD / Sentinel / PRAC-type findings released via ACIP slides, MMWR, or papers (no public VSD raw dashboard); Tier 3 = regulator label/safety communications. Detecting a signal and later classifying it as not confirmed is normal system behavior — not an anomaly to hide or amplify.

4. Documented Adverse Events

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)
10	INFLUENZA (SEASONAL) (AFLURIA)	HIV antigen negative clinical-coded PT · published top-25	48	GPS rank 33 (EBGM=30.97); PRR rank 5 (PRR=1033.1137); ROR rank 5 (ROR=1034.9999); BCPNN rank 35 (IC_LB=4.5461)
11	INFLUENZA (H1N1) (H1N1 (MONOVALENT) (MEDIMMUNE))	Contraindication to vaccination clinical-coded PT · published top-25	96	GPS rank 6 (EBGM=58.75); PRR rank 33 (PRR=155.4578); ROR rank 32 (ROR=157.0347); BCPNN rank 11 (IC_LB=5.3504)
23	INFLUENZA (SEASONAL) (AFLURIA)	Hepatitis B core antibody negative clinical-coded PT	47	GPS rank 58 (EBGM=24.65); PRR rank 36 (PRR=183.9255); ROR rank 36 (ROR=184.2529); BCPNN rank 46 (IC_LB=4.363)
29	INFLUENZA (SEASONAL) (FLUMIST QUADRIVALENT)	Influenza A virus test positive clinical-coded PT	52	GPS rank 53 (EBGM=25.43); PRR rank 52 (PRR=107.2024); ROR rank 53 (ROR=108.008); BCPNN rank 31 (IC_LB=4.6217)
30	INFLUENZA (SEASONAL) (AFLURIA)	HIV antibody negative clinical-coded PT	49	GPS rank 61 (EBGM=24.2); PRR rank 41 (PRR=147.1586); ROR rank 41 (ROR=147.4313); BCPNN rank 47 (IC_LB=4.361)
45	INFLUENZA (SEASONAL) (FLUMIST QUADRIVALENT)	Influenza virus test positive clinical-coded PT	25	GPS rank 55 (EBGM=28.0); PRR rank 43 (PRR=140.5625); ROR rank 43 (ROR=141.0695); BCPNN rank 95 (IC_LB=3.7598)
51	INFLUENZA (SEASONAL) (AFLURIA)	Liquid product physical issue clinical-coded PT	22	GPS rank 59 (EBGM=27.77); PRR rank 26 (PRR=315.6736); ROR rank 26 (ROR=315.9369); BCPNN rank 151 (IC_LB=3.4168)
53	INFLUENZA (SEASONAL) (FLUCELVAX QUADRIVALENT)	Prenatal screening test clinical-coded PT	27	GPS rank 74 (EBGM=23.59); PRR rank 53 (PRR=121.7024); ROR rank 55 (ROR=122.013); BCPNN rank 91 (IC_LB=3.7925)
61	INFLUENZA (SEASONAL) (AFLURIA)	Hepatitis C antibody negative clinical-coded PT	48	GPS rank 84 (EBGM=19.27); PRR rank 82 (PRR=68.8742); ROR rank 82 (ROR=68.9983); BCPNN rank 60 (IC_LB=4.0847)
62	INFLUENZA (SEASONAL) (FLUMIST QUADRIVALENT)	Exposure via direct contact clinical-coded PT	15	GPS rank 32 (EBGM=38.23); PRR rank 27 (PRR=265.0608); ROR rank 28 (ROR=265.6355); BCPNN rank 222 (IC_LB=3.0113)
68	INFLUENZA (SEASONAL) (FLUMIST QUADRIVALENT)	Drug administration error clinical-coded PT	46	GPS rank 83 (EBGM=19.95); PRR rank 94 (PRR=55.2424); ROR rank 95 (ROR=55.6061); BCPNN rank 56 (IC_LB=4.1588)
69	INFLUENZA (SEASONAL) (FLULAVAL)	Pharmaceutical product complaint clinical-coded PT	16	GPS rank 12 (EBGM=53.16); PRR rank 49 (PRR=151.2448); ROR rank 50 (ROR=151.4515); BCPNN rank 217 (IC_LB=3.0332)
76	INFLUENZA (SEASONAL) (AFLURIA)	Hepatitis B surface antigen negative clinical-coded PT	50	GPS rank 109 (EBGM=15.93); PRR rank 90 (PRR=60.3454); ROR rank 91 (ROR=60.4584); BCPNN rank 64 (IC_LB=4.0585)
82	INFLUENZA (SEASONAL) (FLUMIST)	Influenza virus test positive clinical-coded PT	31	GPS rank 102 (EBGM=18.77); PRR rank 85 (PRR=69.1703); ROR rank 85 (ROR=69.284); BCPNN rank 100 (IC_LB=3.7182)
93	INFLUENZA (SEASONAL) (FLUCELVAX QUADRIVALENT)	Influenza A virus test positive clinical-coded PT	34	GPS rank 69 (EBGM=24.35); PRR rank 118 (PRR=42.7688); ROR rank 118 (ROR=42.9043); BCPNN rank 107 (IC_LB=3.6753)

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.

▶ Strong Evidence

Injection site reactions: 40–65% (pain). Strong
Systemic reactions: Fever (5–15% in young children), fatigue, headache, myalgia. Strong
Oculorespiratory syndrome (ORS): Transient red eyes, cough, wheezing within 24 hours of IIV. Reported primarily in Canada with one specific product in 2000–2001. Self-limited. Strong
Anaphylaxis: ~1–2 per million doses. Strong
Wheezing (LAIV in young children with asthma): Contraindication in children <2 and those with asthma. Strong

▶ Moderate Evidence

GBS: ~1–2 excess cases per million doses with seasonal IIV (vs. ~1 per 100,000 with 1976 swine flu vaccine). Evidence is stronger for the 1976 vaccine specifically. Moderate

▶ No Causal Association

Autism: No association. IOM (2012) rejected causality. No Association
Narcolepsy (U.S. seasonal vaccines): The narcolepsy signal was specific to Pandemrix (AS03-adjuvanted, used in Europe). No signal with U.S. seasonal vaccines. No Association

5. Disease Prevention Benefits

Metric	Pre-Vaccine / No Vaccination	With Vaccination
Pediatric influenza hospitalizations (U.S., annual)	~20,000–60,000 (children <5)	VE against pediatric hospitalization: ~40–60% in most seasons; prevents thousands of hospitalizations annually
Pediatric influenza deaths (U.S., annual)	~100–200 reported (underestimated)	~50–80% of pediatric deaths occur in unvaccinated children; vaccination reduces ICU admission risk by ~74%
Maternal influenza vaccination	—	Reduces influenza in infants <6 months by ~50–70% (infants cannot be vaccinated before 6 months)

Source: CDC MMWR, FluView; CDC Pink Book. Effectiveness varies by season. In the 2023–24 season, pediatric VE against hospitalization was ~52–61%, and >80% of influenza-associated pediatric deaths occurred in unvaccinated children.

Disease Burden Over Time

Reported U.S. disease burden by year. The dashed vertical line marks vaccine introduction. Hover or tap data points for values; use arrow keys when a chart has focus.

ⓘ About these charts: These are accessible SVG line charts with keyboard navigation, hover tooltips, and an underlying data table (expand below). The dashed vertical line marks the year of vaccine introduction. Reported cases undercount true incidence; case definitions, reporting practices, and diagnostic methods have changed over time. See Section 5 for additional context and pre-vs-post era comparisons.

7. Evidence Summary

Influenza vaccines differ fundamentally from other childhood vaccines in their variable effectiveness (10–60%), annual reformulation, and the resulting constant need for new post-licensure safety and effectiveness data each season. The safety profile for seasonal IIV is well-established after decades of use in hundreds of millions of annual doses. The primary historical safety concern — the 1976 GBS signal — has not been replicated at comparable magnitude with seasonal vaccines. The narcolepsy signal was adjuvant- and product-specific (Pandemrix). The main evidence limitation is the inherent inability to fully evaluate very rare adverse events for each new seasonal formulation, which is mitigated by the consistency of the manufacturing platform and the extensive passive and active surveillance infrastructure.

8. International Surveillance & Global Data

Quick links to public pharmacovigilance databases and trial registries relevant to Influenza Vaccine. Reporting counts do not establish causality.

Note: Spontaneous reports are unverified observations. Compare with epidemiological studies in Sections 3–6 before drawing conclusions.

9. Curated Adverse Event Literature

Curated peer-reviewed literature linking specific adverse events to Influenza 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.

Disclaimer: Published reports describe observations and associations; they do not establish population incidence or causality.

10. Key References

IOM. Adverse Effects of Vaccines: Evidence and Causality. National Academies Press; 2012.
CDC. Pink Book — Influenza chapter. cdc.gov/pinkbook
Schonberger LB, et al. Guillain-Barré syndrome following vaccination in the National Influenza Immunization Program, United States, 1976–1977. Am J Epidemiol. 1979;110(2):105–123.
Nohynek H, et al. AS03 adjuvanted AH1N1 vaccine associated with an abrupt increase in the incidence of childhood narcolepsy in Finland. PLoS One. 2012;7(3):e33536.
CDC. FluView — Weekly U.S. Influenza Surveillance Report. cdc.gov/flu/weekly
CDC. VSD. cdc.gov/vaccine-safety/about/vsd.html
CDC/FDA. VAERS. vaers.hhs.gov

1. Basic Information

Disease Protected Against

CDC Schedule (U.S., 2025)

Notable Historical Safety Events

Documented Adverse Events (HRSA VICP)

WHO Causality Assessment Methodology

Important Notes

Ingredients (Package Insert)

Antigens

Adjuvants

Preservatives

Excipients & residuals

Causality assessment & potential mechanisms

2. Pre-Licensure Clinical Trial Data

Licensure trial design (ICAN / OpenVAERS)

Most Common Adverse Reactions (Seasonal IIV)

Key Limitations

3. Post-Licensure Safety Data

VSD Findings

VAERS Reporting Data — Halma & Varon (2025), DARE-SAFE

Passive Surveillance: AE Type Breakdown (Multi-System)

VAERS (United States)

Canada Vigilance (Canada)

JADER (PMDA, Japan)

EudraVigilance (EU)

SurVigilance: VigiAccess · Lareb · DAEN · DMA · Medsafe

VigiAccess (WHO)

Lareb (Netherlands)

DAEN (Australia)

DMA (Denmark)

Medsafe (New Zealand)

Pharmacovigilance Lot Signal Detection — Hypothesis-Generating Only

Other Pharmacovigilance Systems

Canada Vigilance (Health Canada)

JADER (PMDA, Japan)

VigiAccess (WHO)

Lareb (Netherlands)

DAEN (Australia)

Active Pharmacovigilance (Defined-Population Surveillance)

CDC Vaccine Safety Datalink (VSD)

AusVaxSafety (Australia)

4. Documented Adverse Events

Rank-aggregated VAERS signal detection (rankv)

▶ Strong Evidence

▶ Moderate Evidence

▶ No Causal Association

5. Disease Prevention Benefits

Disease Burden Over Time

7. Evidence Summary

8. International Surveillance & Global Data

9. Curated Adverse Event Literature

10. Key References

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