A perspective on potential antibody-dependent enhancement of SARS-CoV-2

Ann M. Arvin (), Katja Fink, Michael A. Schmid, Andrea Cathcart, Roberto Spreafico, Colin Havenar-Daughton, Antonio Lanzavecchia, Davide Corti and Herbert W. Virgin ()
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Ann M. Arvin: Vir Biotechnology
Katja Fink: Vir Biotechnology
Michael A. Schmid: Vir Biotechnology
Andrea Cathcart: Vir Biotechnology
Roberto Spreafico: Vir Biotechnology
Colin Havenar-Daughton: Vir Biotechnology
Antonio Lanzavecchia: Vir Biotechnology
Davide Corti: Vir Biotechnology
Herbert W. Virgin: Vir Biotechnology

Nature, 2020, vol. 584, issue 7821, 353-363

Abstract: Abstract Antibody-dependent enhancement (ADE) of disease is a general concern for the development of vaccines and antibody therapies because the mechanisms that underlie antibody protection against any virus have a theoretical potential to amplify the infection or trigger harmful immunopathology. This possibility requires careful consideration at this critical point in the pandemic of coronavirus disease 2019 (COVID-19), which is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Here we review observations relevant to the risks of ADE of disease, and their potential implications for SARS-CoV-2 infection. At present, there are no known clinical findings, immunological assays or biomarkers that can differentiate any severe viral infection from immune-enhanced disease, whether by measuring antibodies, T cells or intrinsic host responses. In vitro systems and animal models do not predict the risk of ADE of disease, in part because protective and potentially detrimental antibody-mediated mechanisms are the same and designing animal models depends on understanding how antiviral host responses may become harmful in humans. The implications of our lack of knowledge are twofold. First, comprehensive studies are urgently needed to define clinical correlates of protective immunity against SARS-CoV-2. Second, because ADE of disease cannot be reliably predicted after either vaccination or treatment with antibodies—regardless of what virus is the causative agent—it will be essential to depend on careful analysis of safety in humans as immune interventions for COVID-19 move forward.

Date: 2020
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DOI: 10.1038/s41586-020-2538-8

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