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Mapping monoclonal anti-SARS-CoV-2 antibody repertoires against diverse coronavirus antigens
de Souza, Matheus Oliveira Madan, Bharat Teng, I-Ting Huang, Aric Liu, Lihong Fahad, Ahmed S. Lopez Acevedo, Sheila N. Pan, Xiaoli Sastry, Mallika Gutierrez-Gonzalez, Matias
de Souza, Matheus Oliveira
Madan, Bharat
Teng, I-Ting
Huang, Aric
Liu, Lihong
Fahad, Ahmed S.
Lopez Acevedo, Sheila N.
Pan, Xiaoli
Sastry, Mallika
Gutierrez-Gonzalez, Matias
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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.
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Date
2022-09-02
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Frontiers Media
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Keywords
SARS-CoV-2, Yeast display, Betacoronaviruses, SARS-CoV-2 variants, Cross-reactive antibodies
Citation
de Souza MO, Madan B, Teng I-T, Huang A, Liu L, Fahad AS, Lopez Acevedo SN, Pan X, Sastry M, Gutierrez-Gonzalez M, Yin MT, Zhou T, Ho DD, Kwong PD and DeKosky BJ (2022) Mapping monoclonal anti-SARS-CoV-2 antibody repertoires against diverse coronavirus antigens. Front. Immunol. 13:977064. doi: 10.3389/fimmu.2022.977064