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Anti-platelet factor 4 antibodies causing VITT do not cross-react with SARS-CoV-2 spike protein.
- Source :
-
Blood [Blood] 2021 Oct 07; Vol. 138 (14), pp. 1269-1277. - Publication Year :
- 2021
-
Abstract
- 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.<br /> (© 2021 by The American Society of Hematology.)
- Subjects :
- Adult
Aged
Aged, 80 and over
Blood Platelets immunology
COVID-19 immunology
Cohort Studies
Epitopes immunology
Female
Heparin metabolism
Humans
Immunoglobulin G immunology
Male
Middle Aged
Protein Binding
Protein Domains
Purpura, Thrombocytopenic, Idiopathic blood
Spike Glycoprotein, Coronavirus chemistry
Young Adult
Antibodies adverse effects
COVID-19 Vaccines adverse effects
Cross Reactions immunology
Platelet Factor 4 immunology
Purpura, Thrombocytopenic, Idiopathic etiology
Purpura, Thrombocytopenic, Idiopathic immunology
Spike Glycoprotein, Coronavirus immunology
Subjects
Details
- Language :
- English
- ISSN :
- 1528-0020
- Volume :
- 138
- Issue :
- 14
- Database :
- MEDLINE
- Journal :
- Blood
- Publication Type :
- Academic Journal
- Accession number :
- 34280256
- Full Text :
- https://doi.org/10.1182/blood.2021012938