A vaccine-induced public antibody protects against SARS-CoV-2 and emerging variants

• Published in: Immunity (Cambridge, Mass.) Mass.), 2021-09, Vol.54 (9), p.2159-2166.e6
• Main Authors: Schmitz, Aaron J., Turner, Jackson S., Liu, Zhuoming, Zhou, Julian Q., Aziati, Ishmael D., Chen, Rita E., Joshi, Astha, Bricker, Traci L., Darling, Tamarand L., Adelsberg, Daniel C., Altomare, Clara G., Alsoussi, Wafaa B., Case, James Brett, VanBlargan, Laura A., Lei, Tingting, Thapa, Mahima, Amanat, Fatima, Jeevan, Trushar, Fabrizio, Thomas, O’Halloran, Jane A., Shi, Pei-Yong, Presti, Rachel M., Webby, Richard J., Krammer, Florian, Whelan, Sean P.J., Bajic, Goran, Diamond, Michael S., Boon, Adrianus C.M., Ellebedy, Ali H.
• Format: Article
• Language: English
• Subjects: Animals; Antibodies, Monoclonal - metabolism; Antibodies, Neutralizing - metabolism; Antibodies, Viral - metabolism; B cell; B-Lymphocytes - immunology; Cells, Cultured; Clone Cells; COVID-19 - immunology; COVID-19 Vaccines - immunology; Cricetinae; Disease Models, Animal; germinal center; Germinal Center - immunology; hamster; Humans; Lung - virology; lymph node; mRNA vaccine; Neutralization Tests; neutralizing antibodies; public clone; receptor binding domain; SARS-CoV-2; SARS-CoV-2 - physiology; Spike Glycoprotein, Coronavirus - immunology; spike protein; Vaccination; Viral Load
• ISSN: 1074-7613; 1097-4180; 1097-4180
• DOI: 10.1016/j.immuni.2021.08.013

The emergence of SARS-CoV-2 antigenic variants with increased transmissibility is a public health threat. Some variants show substantial resistance to neutralization by SARS-CoV-2 infection- or vaccination-induced antibodies. Here, we analyzed receptor binding domain-binding monoclonal antibodies derived from SARS-CoV-2 mRNA vaccine-elicited germinal center B cells for neutralizing activity against the WA1/2020 D614G SARS-CoV-2 strain and variants of concern. Of five monoclonal antibodies that potently neutralized the WA1/2020 D614G strain, all retained neutralizing capacity against the B.1.617.2 variant, four also neutralized the B.1.1.7 variant, and only one, 2C08, also neutralized the B.1.351 and B.1.1.28 variants. 2C08 reduced lung viral load and morbidity in hamsters challenged with the WA1/2020 D614G, B.1.351, or B.1.617.2 strains. Clonal analysis identified 2C08-like public clonotypes among B cells responding to SARS-CoV-2 infection or vaccination in 41 out of 181 individuals. Thus, 2C08-like antibodies can be induced by SARS-CoV-2 vaccines and mitigate resistance by circulating variants of concern. [Display omitted] •2C08 is a germinal center B cell-derived anti-SARS-CoV-2 human monoclonal antibody•2C08 protects hamsters against challenge with B.1.351 and B.1.617.2 SARS-CoV-2 strains•2C08 recognizes a conserved epitope in the receptor-binding domain of SARS-CoV-2 spike•2C08-like clonotypes are induced after SARS-CoV-2 infection and vaccination in humans SARS-CoV-2 variants with increased transmissibility are a public health threat. Schmitz et al. characterize 2C08, a human monoclonal antibody derived from a SARS-CoV-2 vaccine-induced germinal center B cell. 2C08 possesses a broad and potent neutralization capacity and protects hamsters against challenge with D614G, B.1.351, or B.1.617.2 strains. Public 2C08-like clones can be elicited by both SARS-CoV-2 infection and vaccination.