Anti-platelet factor 4 antibodies causing VITT do not cross-react with SARS-CoV-2 spike protein.
Adult
Aged
Aged, 80 and over
Antibodies
/ adverse effects
Blood Platelets
/ immunology
COVID-19
/ immunology
COVID-19 Vaccines
/ adverse effects
Cohort Studies
Cross Reactions
/ immunology
Epitopes
/ immunology
Female
Heparin
/ metabolism
Humans
Immunoglobulin G
/ immunology
Male
Middle Aged
Platelet Factor 4
/ immunology
Protein Binding
Protein Domains
Purpura, Thrombocytopenic, Idiopathic
/ blood
Spike Glycoprotein, Coronavirus
/ chemistry
Young Adult
Journal
Blood
ISSN: 1528-0020
Titre abrégé: Blood
Pays: United States
ID NLM: 7603509
Informations de publication
Date de publication:
07 10 2021
07 10 2021
Historique:
received:
14
06
2021
accepted:
12
07
2021
pubmed:
20
7
2021
medline:
21
10
2021
entrez:
19
7
2021
Statut:
ppublish
Résumé
Vaccine-induced immune thrombotic thrombocytopenia (VITT) is a severe adverse effect of ChAdOx1 nCoV-19 COVID-19 vaccine (Vaxzevria) and Janssen Ad26.COV2.S COVID-19 vaccine, and it is associated with unusual thrombosis. VITT is caused by anti-platelet factor 4 (PF4) antibodies activating platelets through their FcγRIIa receptors. Antibodies that activate platelets through FcγRIIa receptors have also been identified in patients with COVID-19. These findings raise concern that vaccination-induced antibodies against anti-SARS-CoV-2 spike protein cause thrombosis by cross-reacting with PF4. Immunogenic epitopes of PF4 and SARS-CoV-2 spike protein were compared using in silico prediction tools and 3D modeling. The SARS-CoV-2 spike protein and PF4 share at least 1 similar epitope. Reactivity of purified anti-PF4 antibodies from patients with VITT was tested against recombinant SARS-CoV-2 spike protein. However, none of the affinity-purified anti-PF4 antibodies from 14 patients with VITT cross-reacted with SARS-CoV-2 spike protein. Sera from 222 polymerase chain reaction-confirmed patients with COVID-19 from 5 European centers were tested by PF4-heparin enzyme-linked immunosorbent assays and PF4-dependent platelet activation assays. We found anti-PF4 antibodies in sera from 19 (8.6%) of 222 patients with COVID-19. However, only 4 showed weak to moderate platelet activation in the presence of PF4, and none of those patients developed thrombotic complications. Among 10 (4.5%) of 222 patients who had COVID-19 with thrombosis, none showed PF4-dependent platelet-activating antibodies. In conclusion, antibodies against PF4 induced by vaccination do not cross-react with the SARS-CoV-2 spike protein, indicating that the intended vaccine-induced immune response against SARS-CoV-2 spike protein is not the trigger of VITT. PF4-reactive antibodies found in patients with COVID-19 in this study were not associated with thrombotic complications.
Identifiants
pubmed: 34280256
pii: S0006-4971(21)01370-7
doi: 10.1182/blood.2021012938
pmc: PMC8294553
doi:
Substances chimiques
Antibodies
0
COVID-19 Vaccines
0
Epitopes
0
Immunoglobulin G
0
Spike Glycoprotein, Coronavirus
0
spike protein, SARS-CoV-2
0
Platelet Factor 4
37270-94-3
Heparin
9005-49-6
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
1269-1277Commentaires et corrections
Type : CommentIn
Informations de copyright
© 2021 by The American Society of Hematology.
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