Статья

Anti–platelet factor 4 antibodies causing VITT do not cross-react with SARS-CoV-2 spike protein

Andreas GreinacherInstitute of Immunology and Transfusion Medicine, Department of Transfusion Medicine, Universitätsmedizin Greifswald, Greifswald, Germany;Kathleen SellengInstitute of Immunology and Transfusion Medicine, Department of Transfusion Medicine, Universitätsmedizin Greifswald, Greifswald, Germany;Julia MayerleDepartment of Medicine II, University Hospital Munich, and German Centre for Infection Research (DZIF) (partner site Munich), Munich, Germany;Raghavendra PalankarInstitute of Immunology and Transfusion Medicine, Department of Transfusion Medicine, Universitätsmedizin Greifswald, Greifswald, Germany;Jan WescheInstitute of Immunology and Transfusion Medicine, Department of Transfusion Medicine, Universitätsmedizin Greifswald, Greifswald, Germany;Sven ReicheDepartment of Experimental Animal Facilities and Biorisk Management, Friedrich-Loeffler Institut, Greifswald, Germany;Andrea AebischerDepartment of Experimental Animal Facilities and Biorisk Management, Friedrich-Loeffler Institut, Greifswald, Germany;Theodore E. WarkentinDepartment of Pathology and Molecular Medicine, and Department of Medicine, McMaster University, Hamilton, ON, Canada;Maximilian MuenchhoffMax von Pettenkofer Institute, Virology, Ludwig Maximilians University of Munich, and DZIF, Munich, Germany;Johannes C. HellmuthDepartment of Medicine III, University Hospital Munich, Munich, Germany;Oliver T. KepplerMax von Pettenkofer Institute, Virology, Ludwig Maximilians University of Munich, and DZIF, Munich, Germany;Daniel DuerschmiedHeart Center Freiburg University, Cardiology and Angiology I and Medical Intensive Care, Medical Center,Achim LotherHeart Center Freiburg University, Cardiology and Angiology I and Medical Intensive Care, Medical Center,Siegbert RiegDivision of Infectious Diseases, Department of Medicine II, Faculty of Medicine, Medical Center, University of Freiburg, Freiburg, Germany;Meinrad GawazDepartment of Cardiology and Angiology, University Hospital Tübingen, Eberhard Karls University Tübingen, Tübingen, Germany;Karin Anne Lydia MuellerDepartment of Cardiology and Angiology, University Hospital Tübingen, Eberhard Karls University Tübingen, Tübingen, Germany;Christian ScheerMatthias NappKlaus HahnenkampGuglielmo LuccheseDepartment of Neurology, University Medicine Greifswald, Greifswald, Germany;Antje VogelgesangDepartment of Neurology, University Medicine Greifswald, Greifswald, Germany;Agnes FlöelDepartment of Neurology, University Medicine Greifswald, Greifswald, Germany;Piero LovreglioInterdisciplinary Department of Medicine, University of Bari Aldo Moro, Bari, Italy; andAngela StufanoInterdisciplinary Department of Medicine, University of Bari Aldo Moro, Bari, Italy; andRolf MarschalekInstitute of Pharmacology Biology, Biocenter, Goethe University, Frankfurt am Main, GermanyThomas ThieleInstitute of Immunology and Transfusion Medicine, Department of Transfusion Medicine, Universitätsmedizin Greifswald, Greifswald, Germany;for the Immune-Response in COVID-19 Vaccination Study Group

2021en

ABI

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.

Перевод пока недоступен

Идентификаторы

DOI: 10.1182/blood.2021012938

Цитирования и источники

Цитирований: 2Использованных источников: 0

Показатели — AkademScholar