Blood · 2021
Anti-platelet factor 4 antibodies causing VITT do not cross-react with SARS-CoV-2 spike protein.
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Greinacher Andreas, Selleng Kathleen, Mayerle Julia, Palankar Raghavendra, Wesche Jan, Reiche Sven, Aebischer Andrea, Warkentin Theodore E, Muenchhoff Maximilian, Hellmuth Johannes C, Keppler Oliver T, Duerschmied Daniel, Lother Achim, Rieg Siegbert, Gawaz Meinrad Paul, Mueller Karin Anne Lydia, Scheer Christian S, Napp Matthias, Hahnenkamp Klaus, Lucchese Guglielmo, Vogelgesang Antje, Flöel Agnes, Lovreglio Piero, Stufano Angela, Marschalek Rolf, Thiele Thomas, Immune-Response in COVID-19 Vaccination Study Group
Аннотация
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.