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Front Immunol . Mapping monoclonal anti-SARS-CoV-2 antibody repertoires against diverse coronavirus antigens

tetano

Editor, Senior Moderator
Front Immunol


. 2022 Sep 2;13:977064.
doi: 10.3389/fimmu.2022.977064. eCollection 2022.
Mapping monoclonal anti-SARS-CoV-2 antibody repertoires against diverse coronavirus antigens


Matheus Oliveira de Souza[SUP] 1 2 [/SUP], Bharat Madan[SUP] 1 2 [/SUP], I-Ting Teng[SUP] 3 [/SUP], Aric Huang[SUP] 1 [/SUP], Lihong Liu[SUP] 4 [/SUP], Ahmed S Fahad[SUP] 1 [/SUP], Sheila N Lopez Acevedo[SUP] 1 [/SUP], Xiaoli Pan[SUP] 1 [/SUP], Mallika Sastry[SUP] 3 [/SUP], Matias Gutierrez-Gonzalez[SUP] 2 [/SUP], Michael T Yin[SUP] 5 [/SUP], Tongqing Zhou[SUP] 3 [/SUP], David D Ho[SUP] 4 [/SUP], Peter D Kwong[SUP] 3 6 [/SUP], Brandon J DeKosky[SUP] 1 2 7 8 [/SUP]



Affiliations

Abstract

Variants of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have emerged continuously, challenging the effectiveness of vaccines, diagnostics, and treatments. Moreover, the possibility of the appearance of a new betacoronavirus with high transmissibility and high fatality is reason for concern. In this study, we used a natively paired yeast display technology, combined with next-generation sequencing (NGS) and massive bioinformatic analysis to perform a comprehensive study of subdomain specificity of natural human antibodies from two convalescent donors. Using this screening technology, we mapped the cross-reactive responses of antibodies generated by the two donors against SARS-CoV-2 variants and other betacoronaviruses. We tested the neutralization potency of a set of the cross-reactive antibodies generated in this study and observed that most of the antibodies produced by these patients were non-neutralizing. We performed a comparison of the specific and non-specific antibodies by somatic hypermutation in a repertoire-scale for the two individuals and observed that the degree of somatic hypermutation was unique for each patient. The data from this study provide functional insights into cross-reactive antibodies that can assist in the development of strategies against emerging SARS-CoV-2 variants and divergent betacoronaviruses.

Keywords: SARS-CoV-2; SARS-CoV-2 variants; betacoronaviruses; cross-reactive antibodies; yeast display.
 
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