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Published on: June 5, 2021
Mapping monoclonal anti-SARS-CoV-2 antibody repertoires against diverse coronavirus antigens
Matheus Oliveira de Souza1,2, Bharat Madan1,2, I-Ting Teng3
1Department of Pharmaceutical Chemistry, The University of Kansas, Lawrence, KS, United States.
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.
Insights
Researchers mapped natural human antibody responses to SARS-CoV-2 variants and other betacoronaviruses. Most identified antibodies were non-neutralizing, highlighting challenges for developing broad-spectrum antivirals.
Area of Science:
- Immunology and Virology
- Infectious Diseases
- Biotechnology
Background:
- Continuous emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants poses a threat to existing medical countermeasures.
- Potential emergence of novel, highly transmissible and fatal betacoronaviruses necessitates proactive research into host immune responses.
Purpose of the Study:
- To comprehensively map the subdomain specificity of natural human antibodies against SARS-CoV-2 variants and other betacoronaviruses.
- To assess the cross-reactivity and neutralization potency of antibodies from convalescent donors.
Main Methods:
- Utilized natively paired yeast display technology for high-throughput antibody screening.
- Employed next-generation sequencing (NGS) and extensive bioinformatic analysis.
- Tested neutralization potency of identified cross-reactive antibodies.
Main Results:
- Mapped cross-reactive antibody responses against SARS-CoV-2 variants and other betacoronaviruses from two convalescent donors.
- Determined that the majority of identified cross-reactive antibodies exhibited non-neutralizing activity.
- Observed patient-specific differences in somatic hypermutation degrees for antibody repertoires.
Conclusions:
- The study provides functional insights into the breadth and limitations of natural antibody responses to coronaviruses.
- Findings can inform the development of broadly protective vaccines and therapeutics against current and future betacoronavirus threats.
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