A key F27I substitution within HCDR1 facilitates the rapid maturation of P2C-1F11-like neutralizing antibodies in a SARS-CoV-2-infected donor

Miao Wang; Qing Fan; Bing Zhou; Haocheng Ye; Senlin Shen; Jiazhen Yu; Lin Cheng; Xiangyang Ge; Bin Ju; Zheng Zhang

doi:10.1016/j.celrep.2022.111335

A key F27I substitution within HCDR1 facilitates the rapid maturation of P2C-1F11-like neutralizing antibodies in a SARS-CoV-2-infected donor

Cell Rep. 2022 Sep 13;40(11):111335. doi: 10.1016/j.celrep.2022.111335. Epub 2022 Aug 23.

Authors

Miao Wang¹, Qing Fan¹, Bing Zhou¹, Haocheng Ye¹, Senlin Shen¹, Jiazhen Yu¹, Lin Cheng¹, Xiangyang Ge¹, Bin Ju², Zheng Zhang³

Affiliations

¹ Institute for Hepatology, National Clinical Research Center for Infectious Disease, Shenzhen Third People's Hospital; the Second Affiliated Hospital, School of Medicine, Southern University of Science and Technology, Shenzhen, Guangdong Province 518112, China.
² Institute for Hepatology, National Clinical Research Center for Infectious Disease, Shenzhen Third People's Hospital; the Second Affiliated Hospital, School of Medicine, Southern University of Science and Technology, Shenzhen, Guangdong Province 518112, China; Guangdong Key Laboratory for Anti-infection Drug Quality Evaluation, Shenzhen, Guangdong Province 518112, China. Electronic address: [email protected].
³ Institute for Hepatology, National Clinical Research Center for Infectious Disease, Shenzhen Third People's Hospital; the Second Affiliated Hospital, School of Medicine, Southern University of Science and Technology, Shenzhen, Guangdong Province 518112, China; Guangdong Key Laboratory for Anti-infection Drug Quality Evaluation, Shenzhen, Guangdong Province 518112, China; Shenzhen Research Center for Communicable Disease Diagnosis and Treatment of Chinese Academy of Medical Science, Shenzhen, Guangdong Province 518112, China. Electronic address: [email protected].

Abstract

Although thousands of anti-SARS-CoV-2 monoclonal neutralizing antibodies (nAbs) have been identified and well characterized, some crucial events in the development of these nAbs during viral infection remain unclear. Using deep sequencing, we explore the dynamics of antibody repertoire in a SARS-CoV-2-infected donor, from whom the potent and broad nAb P2C-1F11 (the parent version of Brii-196) was previously isolated. Further analysis shows a rapid clonal expansion of some SARS-CoV-2-specific antibodies in early infection. Longitudinal tracing of P2C-1F11 lineage antibodies reveals that these elite nAbs were rare. Using sequence alignment, structure modeling, and bioactivity analysis based on site-mutated assay, we demonstrate that a key substitution F27I in heavy chain contributes significantly to the maturation of P2C-1F11-like antibodies. Overall, our findings elucidate the developmental process and maturation pathway of P2C-1F11, providing some important information for the design of novel immunogens to elicit more potent nAbs against SARS-CoV-2 infection.

Keywords: CP: Immunology; P2C-1F11 lineage; SARS-CoV-2; antibody repertoire; deep sequencing; neutralizing antibody.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Antibodies, Monoclonal
Antibodies, Neutralizing
Antibodies, Viral
COVID-19*
Humans
SARS-CoV-2*

Substances

Antibodies, Monoclonal
Antibodies, Neutralizing
Antibodies, Viral