AUTHOR=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. TITLE=Mapping monoclonal anti-SARS-CoV-2 antibody repertoires against diverse coronavirus antigens JOURNAL=Frontiers in Immunology VOLUME=13 YEAR=2022 URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2022.977064 DOI=10.3389/fimmu.2022.977064 ISSN=1664-3224 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.