Anti–platelet factor 4 antibodies causing VITT do not cross-react with SARS-CoV-2 spike protein-Reference-Cited by-同舟云学术

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

Published:2021-10-07 Issue:14 Volume:138 Page:1269-1277
ISSN:0006-4971
Container-title:Blood
language:en
Short-container-title:

Author:

Greinacher Andreas¹^ORCID,Selleng Kathleen¹,Mayerle Julia²^ORCID,Palankar Raghavendra¹^ORCID,Wesche Jan¹^ORCID,Reiche Sven³,Aebischer Andrea³,Warkentin Theodore E.⁴^ORCID,Muenchhoff Maximilian⁵^ORCID,Hellmuth Johannes C.⁶^ORCID,Keppler Oliver T.⁵,Duerschmied Daniel⁷^ORCID,Lother Achim⁷⁸^ORCID,Rieg Siegbert⁹^ORCID,Gawaz Meinrad Paul¹⁰,Mueller Karin Anne Lydia¹⁰,Scheer Christian S.¹¹^ORCID,Napp Matthias¹¹,Hahnenkamp Klaus¹¹,Lucchese Guglielmo¹²,Vogelgesang Antje¹²,Flöel Agnes¹²,Lovreglio Piero¹³,Stufano Angela¹³,Marschalek Rolf¹⁴^ORCID,Thiele Thomas¹,

Affiliation:

1. Institute of Immunology and Transfusion Medicine, Department of Transfusion Medicine, Universitätsmedizin Greifswald, Greifswald, Germany;

2. Department of Medicine II, University Hospital Munich, and German Centre for Infection Research (DZIF) (partner site Munich), Munich, Germany;

3. Department of Experimental Animal Facilities and Biorisk Management, Friedrich-Loeffler Institut, Greifswald, Germany;

4. Department of Pathology and Molecular Medicine, and Department of Medicine, McMaster University, Hamilton, ON, Canada;

5. Max von Pettenkofer Institute, Virology, Ludwig Maximilians University of Munich, and DZIF, Munich, Germany;

6. Department of Medicine III, University Hospital Munich, Munich, Germany;

7. Heart Center Freiburg University, Cardiology and Angiology I and Medical Intensive Care, Medical Center,

8. Institute of Experimental and Clinical Pharmacology and Toxicology, and

9. Division of Infectious Diseases, Department of Medicine II, Faculty of Medicine, Medical Center, University of Freiburg, Freiburg, Germany;

10. Department of Cardiology and Angiology, University Hospital Tübingen, Eberhard Karls University Tübingen, Tübingen, Germany;

11. Department of Anesthesiology and Intensive Care Medicine, and

12. Department of Neurology, University Medicine Greifswald, Greifswald, Germany;

13. Interdisciplinary Department of Medicine, University of Bari Aldo Moro, Bari, Italy; and

14. Institute of Pharmacology Biology, Biocenter, Goethe University, Frankfurt am Main, Germany

Abstract

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.

Publisher

American Society of Hematology

Subject

Cell Biology,Hematology,Immunology,Biochemistry

Link

http://ashpublications.org/blood/article-pdf/138/14/1269/1827137/bloodbld2021012938.pdf

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