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

• Published in: Frontiers in immunology 2022-09, Vol.13, p.977064-977064
• Main Authors: 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, Yin, Michael T., Zhou, Tongqing, Ho, David D., Kwong, Peter D., DeKosky, Brandon J.
• Format: Article
• Language: English
• Subjects: betacoronaviruses; cross-reactive antibodies; Immunology; SARS-CoV-2; SARS-CoV-2 variants; yeast display
• ISSN: 1664-3224; 1664-3224
• DOI: 10.3389/fimmu.2022.977064

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.