The functions of SARS-CoV-2 neutralizing and infection-enhancing antibodies in vitro and in mice and nonhuman primates

作者: Dapeng Li , Robert J Edwards , Kartik Manne , David R Martinez , Alexandra Schäfer

DOI: 10.1101/2020.12.31.424729

关键词: In vitroCytokineVirologyVirusMedicineAntibodyDiseaseFc receptorBronchoalveolar lavageIn vivo

摘要: SARS-CoV-2 neutralizing antibodies (NAbs) protect against COVID-19, making them a focus of vaccine design. A safety concern regarding is whether they mediate disease enhancement. Here, we isolated potent NAbs the receptor-binding domain (RBD) and N-terminal (NTD) spike protein from individuals with acute or convalescent history SARS-CoV-1 infection. Cryo-electron microscopy RBD NTD demonstrated function-specific modes antibody binding. Select also Fc receptor-γ (FcγR)-mediated enhancement virus infection in vitro , while five non-neutralizing mediated FcγR-independent However, both infection-enhancing protected challenge non-human primates mice. One 30 monkeys infused enhancing had lung pathology bronchoalveolar lavage cytokine evidence suggestive enhanced disease. Thus, these assessments antibody-mediated do not necessarily indicate biologically relevant vivo

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