Landscape of human antibody recognition of the SARS-CoV-2 receptor binding domain

Wheatley, AK; Pymm, P; Esterbauer, R; Dietrich, MH; Lee, WS; Drew, D; Kelly, HG; Chan, LJ; Mordant, FL; Black, KA; Adair, A; Tan, HX; Juno, JA; Wragg, KM; Amarasena, T; Lopez, E; Selva, KJ; Haycroft, ER; Cooney, JP; Venugopal, H; Tan, LL; ONeill MT; Allison, CC; Cromer, D; Davenport, MP; Bowen, RA; Chung, AW; Pellegrini, M; Liddament, MT; Glukhova, A; Subbarao, K; Kent, SJ; Tham, WH

Author(s): Wheatley, AK; Pymm, P; Esterbauer, R; Dietrich, MH; Lee, WS; Drew, D; Kelly, HG; Chan, LJ; Mordant, FL; Black, KA; Adair, A; Tan, HX; Juno, JA; Wragg, KM; Amarasena, T; Lopez, E; Selva, KJ; Haycroft, ER; Cooney, JP; Venugopal, H; Tan, LL; ONeill MT; Allison, CC; Cromer, D; Davenport, MP; Bowen, RA; Chung, AW; Pellegrini, M; Liddament, MT; Glukhova, A; Subbarao, K; Kent, SJ; Tham, WH;
Details: Publication Year 2021-09-25,Volume 37,Issue #2,Page 109822
Journal Title: Cell Reports
Abstract: Potent neutralizing monoclonal antibodies are one of the few agents currently available to treat COVID-19. SARS-CoV-2 variants of concern (VOCs) that carry multiple mutations in the viral spike protein can exhibit neutralization resistance, potentially affecting the effectiveness of some antibody-based therapeutics. Here, the generation of a diverse panel of 91 human, neutralizing monoclonal antibodies provides an in-depth structural and phenotypic definition of receptor binding domain (RBD) antigenic sites on the viral spike. These RBD antibodies ameliorate SARS-CoV-2 infection in mice and hamster models in a dose-dependent manner and in proportion to in vitro, neutralizing potency. Assessing the effect of mutations in the spike protein on antibody recognition and neutralization highlights both potent single antibodies and stereotypic classes of antibodies that are unaffected by currently circulating VOCs, such as B.1.351 and P.1. These neutralizing monoclonal antibodies and others that bind analogous epitopes represent potentially useful future anti-SARS-CoV-2 therapeutics.
Keywords: SARS-CoV-2; anti-viral therapeutics; cryo-EM; crystallography; human antibodies; mAb
Research Division(s): Infectious Diseases And Immune Defence; Structural Biology
PubMed ID: 34610292
Publisher's Version: https://doi.org/10.1016/j.celrep.2021.109822
Open Access at Publisher's Site: https://doi.org/10.1016/j.celrep.2021.109822
Terms of Use/Rights Notice: Refer to copyright notice on published article.
Documents: Wheatley AK, et al_Cell Reports_2021.pdf - (4.57MB, application/pdf)

Creation Date: 2021-10-12 07:30:17

Last Modified: 2021-10-29 09:18:22