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

[tetano]

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



Affiliations

• PMID: 36119018
• PMCID: PMC9478573
• DOI: 10.3389/fimmu.2022.977064

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.