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Potent neutralizing antibodies from COVID-19 patients define multiple targets of vulnerability.

ABSTRACT: The rapid spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has had a large impact on global health, travel, and economy. Therefore, preventative and therapeutic measures are urgently needed. Here, we isolated monoclonal antibodies from three convalescent coronavirus disease 2019 (COVID-19) patients using a SARS-CoV-2 stabilized prefusion spike protein. These antibodies had low levels of somatic hypermutation and showed a strong enrichment in VH1-69, VH3-30-3, and VH1-24 gene usage. A subset of the antibodies was able to potently inhibit authentic SARS-CoV-2 infection at a concentration as low as 0.007 micrograms per milliliter. Competition and electron microscopy studies illustrate that the SARS-CoV-2 spike protein contains multiple distinct antigenic sites, including several receptor-binding domain (RBD) epitopes as well as non-RBD epitopes. In addition to providing guidance for vaccine design, the antibodies described here are promising candidates for COVID-19 treatment and prevention.

SUBMITTER: Brouwer PJM 

PROVIDER: S-EPMC7299281 | biostudies-literature | 2020 Aug

REPOSITORIES: biostudies-literature

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Potent neutralizing antibodies from COVID-19 patients define multiple targets of vulnerability.

Brouwer Philip J M PJM   Caniels Tom G TG   van der Straten Karlijn K   Snitselaar Jonne L JL   Aldon Yoann Y   Bangaru Sandhya S   Torres Jonathan L JL   Okba Nisreen M A NMA   Claireaux Mathieu M   Kerster Gius G   Bentlage Arthur E H AEH   van Haaren Marlies M MM   Guerra Denise D   Burger Judith A JA   Schermer Edith E EE   Verheul Kirsten D KD   van der Velde Niels N   van der Kooi Alex A   van Schooten Jelle J   van Breemen Mariëlle J MJ   Bijl Tom P L TPL   Sliepen Kwinten K   Aartse Aafke A   Derking Ronald R   Bontjer Ilja I   Kootstra Neeltje A NA   Wiersinga W Joost WJ   Vidarsson Gestur G   Haagmans Bart L BL   Ward Andrew B AB   de Bree Godelieve J GJ   Sanders Rogier W RW   van Gils Marit J MJ  

Science (New York, N.Y.) 20200615 6504

The rapid spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has had a large impact on global health, travel, and economy. Therefore, preventative and therapeutic measures are urgently needed. Here, we isolated monoclonal antibodies from three convalescent coronavirus disease 2019 (COVID-19) patients using a SARS-CoV-2 stabilized prefusion spike protein. These antibodies had low levels of somatic hypermutation and showed a strong enrichment in VH1-69, VH3-30-3, and VH1-24 gen  ...[more]

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