{ "_meta": { "description": "Reusable biological mechanism catalog for vaccine-associated adverse events. Mechanism IDs are referenced by per-vaccine injury tables.", "lastUpdated": "2026-07-16", "schemaVersion": "1.0.0", "sources": [ "IOM/NASEM Adverse Effects of Vaccines: Evidence and Causality (2011–2012)", "HRSA Vaccine Injury Table (VICP)", "Brighton Collaboration AESI companion literature", "CDC VSD / ACIP safety presentations", "Peer-reviewed mechanistic and epidemiologic reviews" ] }, "mechanisms": { "ige_hypersensitivity_anaphylaxis": { "mechanism_id": "ige_hypersensitivity_anaphylaxis", "name": "IgE-mediated hypersensitivity (anaphylaxis)", "category": "hypersensitivity", "summary": "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.", "pathway_steps": [ "Sensitization to antigen or excipient", "IgE cross-linking on mast cells/basophils after re-exposure", "Histamine and inflammatory mediator release", "Systemic capillary leak, bronchospasm, shock within minutes to hours" ], "evidence_level": "High", "applies_to_platforms": ["any"], "typical_time_window_days": [0, 1], "supporting_literature": [ { "label": "IOM — Adverse Effects of Vaccines (anaphylaxis)", "url": "https://nap.nationalacademies.org/catalog/13164/adverse-effects-of-vaccines-evidence-and-causality", "year": 2012, "type": "iom_report" }, { "label": "Brighton Collaboration — Anaphylaxis case definition", "url": "https://brightoncollaboration.org/anaphylaxis-v2/", "type": "regulatory" } ] }, "molecular_mimicry_gbs": { "mechanism_id": "molecular_mimicry_gbs", "name": "Molecular mimicry → Guillain-Barré syndrome", "category": "molecular_mimicry", "summary": "Vaccine- or infection-triggered immune responses cross-react with peripheral-nerve gangliosides or myelin components, producing demyelinating or axonal polyneuropathy.", "pathway_steps": [ "Antigen exposure (vaccine or infection)", "Cross-reactive antibodies or T cells against nerve epitopes", "Complement activation and macrophage-mediated demyelination", "Ascending weakness and areflexia (typical GBS phenotype)" ], "evidence_level": "Moderate", "applies_to_platforms": ["any", "inactivated", "viral_vector"], "typical_time_window_days": [0, 42], "supporting_literature": [ { "label": "IOM — GBS and vaccines evidence review", "url": "https://nap.nationalacademies.org/catalog/13164/adverse-effects-of-vaccines-evidence-and-causality", "year": 2012, "type": "iom_report" } ] }, "molecular_mimicry_itp": { "mechanism_id": "molecular_mimicry_itp", "name": "Immune-mediated thrombocytopenia (ITP)", "category": "molecular_mimicry", "summary": "Cross-reactive antibodies against platelet antigens lead to accelerated platelet destruction, classically described after live measles-containing vaccines within weeks.", "pathway_steps": [ "Immune activation after vaccination", "Anti-platelet antibody formation", "Platelet opsonization and splenic clearance", "Thrombocytopenia with bleeding risk" ], "evidence_level": "Moderate", "applies_to_platforms": ["live_attenuated"], "typical_time_window_days": [0, 42], "supporting_literature": [ { "label": "France EK et al. — ITP after MMR (Pediatrics)", "url": "https://doi.org/10.1542/peds.2007-1578", "year": 2008, "type": "cohort_study" } ] }, "molecular_mimicry_myocarditis": { "mechanism_id": "molecular_mimicry_myocarditis", "name": "Myocarditis / pericarditis immune injury", "category": "innate_inflammation", "summary": "Innate inflammatory response and possible molecular mimicry between spike protein and cardiac proteins can injure myocardium/pericardium, especially after mRNA COVID-19 vaccines in young males.", "pathway_steps": [ "Vaccine antigen expression or presentation", "Innate cytokine response and myocardial inflammation", "Possible cross-reactivity with cardiac epitopes", "Chest pain, troponin elevation, imaging evidence of myocarditis" ], "evidence_level": "High", "applies_to_platforms": ["mrna"], "typical_time_window_days": [0, 7], "supporting_literature": [ { "label": "Heymans S, Cooper LT — Nat Rev Cardiol myocarditis review", "url": "https://pubmed.ncbi.nlm.nih.gov/34887571/", "pmid": "34887571", "year": 2021, "type": "narrative_review" } ] }, "live_vaccine_replication": { "mechanism_id": "live_vaccine_replication", "name": "Uncontrolled live attenuated vaccine replication", "category": "live_replication", "summary": "In immunocompromised or otherwise susceptible hosts, live attenuated vaccine strains can replicate beyond the intended limited infection, causing disseminated disease or organ-specific infection.", "pathway_steps": [ "Live attenuated vaccine administration", "Inadequate host control of replication", "Systemic or tissue-restricted viral/bacterial spread", "Vaccine-strain disease (e.g., measles, varicella, yellow fever)" ], "evidence_level": "High", "applies_to_platforms": ["live_attenuated"], "typical_time_window_days": [0, 365], "supporting_literature": [ { "label": "HRSA Vaccine Injury Table — live vaccine disseminated infection", "url": "https://www.hrsa.gov/vaccine-compensation/vaccine-injury-table", "type": "regulatory" } ] }, "procedural_sirva": { "mechanism_id": "procedural_sirva", "name": "SIRVA — incorrect injection into shoulder structures", "category": "procedural", "summary": "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).", "pathway_steps": [ "Incorrect injection site or angle", "Bursal/joint trauma and inflammation", "Persistent pain and limited mobility" ], "evidence_level": "High", "applies_to_platforms": ["any"], "typical_time_window_days": [0, 2], "supporting_literature": [ { "label": "HRSA — SIRVA on Vaccine Injury Table", "url": "https://www.hrsa.gov/vaccine-compensation/vaccine-injury-table", "type": "regulatory" } ] }, "vasovagal_syncope": { "mechanism_id": "vasovagal_syncope", "name": "Vasovagal (needle) syncope", "category": "vasovagal", "summary": "Pain, anxiety, or orthostatic stress from injection triggers parasympathetic surge with bradycardia and hypotension, producing transient loss of consciousness—common in adolescents.", "pathway_steps": [ "Noxious or anticipatory stimulus", "Vagal activation", "Transient cerebral hypoperfusion", "Syncope ± injury from fall" ], "evidence_level": "High", "applies_to_platforms": ["any"], "typical_time_window_days": [0, 1], "supporting_literature": [ { "label": "CDC — Syncope after vaccination", "url": "https://www.cdc.gov/vaccinesafety/concerns/fainting.html", "type": "regulatory" } ] }, "brachial_neuritis_immune": { "mechanism_id": "brachial_neuritis_immune", "name": "Immune-mediated brachial neuritis", "category": "molecular_mimicry", "summary": "Immune-mediated inflammation of brachial plexus nerves after antigenic stimulation (classically tetanus toxoid-containing vaccines), producing severe shoulder/arm pain and weakness.", "pathway_steps": [ "Antigenic stimulus", "Immune attack on brachial plexus", "Acute pain then paresis" ], "evidence_level": "Moderate", "applies_to_platforms": ["toxoid", "any"], "typical_time_window_days": [0, 28], "supporting_literature": [ { "label": "IOM — brachial neuritis and tetanus toxoid", "url": "https://nap.nationalacademies.org/catalog/13164/adverse-effects-of-vaccines-evidence-and-causality", "year": 2012, "type": "iom_report" } ] }, "febrile_seizure_fever": { "mechanism_id": "febrile_seizure_fever", "name": "Fever-triggered seizure", "category": "innate_inflammation", "summary": "Vaccine-induced fever lowers seizure threshold in susceptible young children; measles-containing vaccines show a well-documented risk window roughly 7–14 days post-dose.", "pathway_steps": [ "Vaccine reactogenicity and fever", "Lowered seizure threshold in susceptible child", "Brief generalized seizure without long-term epilepsy in most cases" ], "evidence_level": "High", "applies_to_platforms": ["live_attenuated", "any"], "typical_time_window_days": [5, 14], "supporting_literature": [ { "label": "Klein NP et al. — MMRV febrile seizures (Pediatrics)", "url": "https://doi.org/10.1542/peds.2010-0665", "year": 2010, "type": "cohort_study" } ] }, "intussusception_lymphoid": { "mechanism_id": "intussusception_lymphoid", "name": "Intussusception after oral rotavirus vaccine", "category": "innate_inflammation", "summary": "Oral rotavirus vaccines can promote lymphoid hyperplasia and altered gut motility that rare­ly lead to telescoping of intestine (intussusception), especially after dose 1.", "pathway_steps": [ "Oral live rotavirus antigen exposure", "Intestinal lymphoid stimulation", "Lead-point formation and telescoping", "Bowel obstruction / ischemia if untreated" ], "evidence_level": "High", "applies_to_platforms": ["live_attenuated", "oral"], "typical_time_window_days": [1, 21], "supporting_literature": [ { "label": "Weintraub ES et al. — intussusception after rotavirus vaccine (NEJM)", "url": "https://doi.org/10.1056/NEJMoa1311738", "year": 2014, "type": "cohort_study" } ] }, "encephalitis_live_virus": { "mechanism_id": "encephalitis_live_virus", "name": "Vaccine-strain encephalitis / encephalomyelitis", "category": "live_replication", "summary": "Live viral vaccines can rarely cause CNS infection or demyelinating encephalomyelitis via direct viral invasion or post-infectious immune attack.", "pathway_steps": [ "Live vaccine virus exposure", "CNS invasion or autoimmune demyelination", "Encephalitis / ADEM clinical syndrome" ], "evidence_level": "Moderate", "applies_to_platforms": ["live_attenuated"], "typical_time_window_days": [0, 42], "supporting_literature": [ { "label": "Brighton Collaboration — encephalitis / ADEM", "url": "https://brightoncollaboration.org/encephalitis-myelitis-and-acute-disseminated-encephalomyelitis-adem/", "type": "regulatory" } ] }, "adjuvant_local_systemic_reactogenicity": { "mechanism_id": "adjuvant_local_systemic_reactogenicity", "name": "Adjuvant-driven local and systemic reactogenicity", "category": "innate_inflammation", "summary": "Aluminum or other adjuvants (e.g., AS01B) amplify innate immune signaling, producing injection-site inflammation and transient systemic symptoms (fever, myalgia, fatigue).", "pathway_steps": [ "Adjuvant pattern-recognition receptor activation", "Local cytokine release", "Systemic acute-phase response" ], "evidence_level": "High", "applies_to_platforms": ["adjuvanted", "subunit", "recombinant_protein"], "typical_time_window_days": [0, 3], "supporting_literature": [ { "label": "CDC — understanding vaccine side effects", "url": "https://www.cdc.gov/vaccines/vac-gen/side-effects.htm", "type": "regulatory" } ] }, "facial_nerve_inflammation": { "mechanism_id": "facial_nerve_inflammation", "name": "Facial nerve inflammation (Bell's palsy-type)", "category": "innate_inflammation", "summary": "Transient inflammatory neuropathy of CN VII has been hypothesized after some vaccines; evidence of causal association is often weak or product-specific.", "pathway_steps": [ "Immune activation", "Facial nerve edema/inflammation", "Unilateral facial weakness" ], "evidence_level": "Low", "applies_to_platforms": ["any", "intranasal"], "typical_time_window_days": [0, 30] }, "yf_viscerotropic": { "mechanism_id": "yf_viscerotropic", "name": "Yellow fever vaccine-associated viscerotropic disease", "category": "live_replication", "summary": "Rare multi-organ failure syndrome after live YF-17D vaccine, resembling wild-type yellow fever, with high case fatality; risk higher in older adults and thymectomy history.", "pathway_steps": [ "Live 17D vaccine administration", "Uncontrolled vaccine virus replication", "Multi-organ failure phenotype" ], "evidence_level": "High", "applies_to_platforms": ["live_attenuated"], "typical_time_window_days": [0, 10], "supporting_literature": [ { "label": "CDC Yellow Book — yellow fever vaccine safety", "url": "https://wwwnc.cdc.gov/travel/yellowbook/2024/infections-diseases/yellow-fever", "type": "regulatory" } ] }, "yf_neurotropic": { "mechanism_id": "yf_neurotropic", "name": "Yellow fever vaccine-associated neurologic disease", "category": "live_replication", "summary": "Rare neurotropic disease after YF-17D (meningitis, encephalitis, GBS-like illness), more often reported in infants and older adults.", "pathway_steps": [ "Live 17D vaccination", "Neuroinvasion or post-vaccinal CNS inflammation", "Neurologic syndrome" ], "evidence_level": "High", "applies_to_platforms": ["live_attenuated"], "typical_time_window_days": [0, 30] }, "tts_adenovector": { "mechanism_id": "tts_adenovector", "name": "Vaccine-induced immune thrombotic thrombocytopenia (VITT/TTS)", "category": "immune_complex", "summary": "Rare anti-PF4 antibody-mediated platelet activation after some adenovirus-vector COVID vaccines, producing thrombosis with thrombocytopenia.", "pathway_steps": [ "Adenovector vaccine exposure", "Anti-PF4 IgG formation", "Platelet activation and thrombosis with low platelets" ], "evidence_level": "High", "applies_to_platforms": ["viral_vector"], "typical_time_window_days": [4, 30] }, "unknown_temporal": { "mechanism_id": "unknown_temporal", "name": "Temporal association — mechanism unknown", "category": "unknown", "summary": "Reports show temporal clustering after vaccination but a specific pathogenic pathway is not established; alternative (coincidental) explanations remain plausible.", "pathway_steps": [ "Temporal association observed", "Insufficient mechanistic evidence for a single pathway" ], "evidence_level": "Hypothetical", "applies_to_platforms": ["any"], "notes": "Use when causality is Possible/Unclassifiable without a validated mechanism." } } }