{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,6]],"date-time":"2026-11-06T11:02:35Z","timestamp":1793962955538,"version":"4.8.0"},"reference-count":38,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2026,2,28]],"date-time":"2026-02-28T00:00:00Z","timestamp":1772236800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Vaccines"],"abstract":"<jats:p>Background\/Objectives: Vaccine-induced immune thrombotic thrombocytopenia (VITT) is a rare but severe immune-mediated adverse event associated with adenoviral vector-based SARS-CoV-2 vaccines. Beyond its clinical relevance, VITT provides a unique human model of vaccine-triggered autoimmunity and immune-thrombosis. This review critically reassesses the immunopathogenic framework of VITT in light of recent evidence. Methods: We conducted a structured narrative review of studies published between 2021 and 2025, focusing on clinical, epidemiological, and mechanistic data relevant to PF4 immunogenicity, platelet activation, and long-term outcomes. Results: Current evidence supports a multistep model in which adenoviral vector components form immunogenic PF4\u2013polyanion complexes that induce high-affinity anti-PF4 IgG antibodies. These antibodies activate platelets via Fc\u03b3RIIa, amplify complement signaling, promote neutrophil extracellular trap formation, and drive endothelial perturbation, establishing a self-sustaining thrombo-inflammatory loop. Recent longitudinal studies refine earlier interpretations by distinguishing persistent anti-PF4 seropositivity from sustained platelet-activating capacity. Epidemiological data support platform-enriched risk rather than absolute platform exclusivity, with a proposed mechanistic \u201cborder zone\u201d for incomplete phenotypes. Conclusions: VITT represents a tractable human model of vaccine-induced autoimmunity in which innate immune activation and multivalent antigen presentation converge to break tolerance. Updated evidence clarifies antibody persistence, platform enrichment, and translational implications, while highlighting unresolved questions regarding host susceptibility and long-term immune regulation.<\/jats:p>","DOI":"10.3390\/vaccines14030225","type":"journal-article","created":{"date-parts":[[2026,3,2]],"date-time":"2026-03-02T10:24:34Z","timestamp":1772447074000},"page":"225","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Vaccine-Induced Immune Thrombotic Thrombocytopenia (VITT): An Immunopathogenic Model of Dysregulated Vaccine-Triggered Immunity"],"prefix":"10.3390","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0613-1074","authenticated-orcid":false,"given":"Carmine","family":"Siniscalchi","sequence":"first","affiliation":[{"name":"Department of Internal Medicine, Parma University Hospital, 43100 Parma, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Manuela","family":"Basaglia","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Parma University Hospital, 43100 Parma, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2398-6135","authenticated-orcid":false,"given":"Antonella","family":"Tufano","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, \u201cFederico II University\u201d Napoli University Hospital, 80078 Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2656-5467","authenticated-orcid":false,"given":"Egidio","family":"Imbalzano","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Messina University Hospital, 98121 Messina, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8484-4598","authenticated-orcid":false,"given":"Pierpaolo","family":"Di Micco","sequence":"additional","affiliation":[{"name":"UOC Medicina Interna, P.O. Pozzuoli, ASL Napoli2 nord, 80078 Pozzuoli, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,2,28]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"2092","DOI":"10.1056\/NEJMoa2104840","article-title":"Thrombotic Thrombocytopenia after ChAdOx1 nCov-19 Vaccination","volume":"384","author":"Greinacher","year":"2021","journal-title":"N. Engl. J. Med."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"2124","DOI":"10.1056\/NEJMoa2104882","article-title":"Thrombosis and Thrombocytopenia after ChAdOx1 nCoV-19 Vaccination","volume":"384","author":"Schultz","year":"2021","journal-title":"N. Engl. J. Med."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"2202","DOI":"10.1056\/NEJMoa2105385","article-title":"Pathologic Antibodies to Platelet Factor 4 after ChAdOx1 nCoV-19 Vaccination","volume":"384","author":"Scully","year":"2021","journal-title":"N. Engl. J. 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