Convergent antibody responses to the SARS-CoV-2 spike protein in convalescent and vaccinated individuals

Abstract

Unrelated individuals can produce genetically similar clones of antibodies, known as public clonotypes, which have been seen in responses to different infectious diseases as well as healthy individuals. Here we identify 37 public clonotypes in memory B cells from convalescent survivors of SARS-CoV-2 infection or in plasmablasts from an individual after vaccination with mRNA-encoded spike protein. We identified 29 public clonotypes, including clones recognizing the receptor-binding domain (RBD) in the spike protein S1 subunit (including a neutralizing, ACE2-blocking clone that protects in vivo ), and others recognizing non-RBD epitopes that bound the S2 domain. Germline-revertant forms of some public clonotypes bound efficiently to spike protein, suggesting these common germline-encoded antibodies are preconfigured for avid recognition. Identification of large numbers of public clonotypes provides insight into the molecular basis of efficacy of SARS-CoV-2 vaccines and sheds light on the immune pressures driving the selection of common viral escape mutants.

Monoclonal antibodies for COVID-19 therapy and SARS-CoV-2 detection

“…Most recently, it has been reported that the combination of COV2-2130 and COV2-2196 can neutralize SARS-CoV-2 variants, including B.1.1.7 (Alpha), B.1.351 (Beta), P.1 (Gamma), B.1429 (Epsilon), B.1617.1, or B.1526 (Iota), in vitro. From the analysis of prophylactic and therapeutic efficacies against B.1.1.7 (Alpha), B.1.351 (Beta), or P.1 (Gamma) in animals, AZD7442 showed promising results [ 105 ]. In November 2021, new data from two phase III trials testing AZD7442 for prophylaxis and post-exposure prophylaxis were released (Table 2 ).…”

Understanding the Secret of SARS-CoV-2 Variants of Concern/Interest and Immune Escape

“…However, it must be recognized that the use of mAbs for longterm treatment or prevention, especially in chronic infected individuals who are immunocompromised, may lead to the emergence of neutralization resistance mutations. In order to avoid selective pressure and immune escape, it is suggested that antibody therapy might consist of a combination of antibodies targeting non-overlapping or highly conserved epitopes (129). Considering the important role of site 484 for antibody binding and neutralization, it is a good strategy to identify monoclonal antibodies from E484K infected individuals (59).…”

A large-scale systematic survey of SARS-CoV-2 antibodies reveals recurring molecular features

“…The public antibody response to SARS-CoV-2 has also been examined by a recent data mining study that focused on identifying public clonotypes [55]. This previous study defined public clonotypes as antibodies with the same IGHV/IGHJ/IGK(L)V/IGK(L)V genes and high similarity of CDR H3 [55]. While multiple public clonotypes were identified using this stringent definition [55], the characterization of public antibody response is likely far from comprehensive.…”

“…The public antibody response to SARS-CoV-2 has also been examined by a recent data mining study that focused on identifying public clonotypes [55]. This previous study defined public clonotypes as antibodies with the same IGHV/IGHJ/IGK(L)V/IGK(L)V genes and high similarity of CDR H3 [55].…”

“…This previous study defined public clonotypes as antibodies with the same IGHV/IGHJ/IGK(L)V/IGK(L)V genes and high similarity of CDR H3 [55]. While multiple public clonotypes were identified using this stringent definition [55], the characterization of public antibody response is likely far from comprehensive. A public antibody response may not always involve a defined pair of IGHV/IGK(L)V genes, especially when either IGHV or IGK(L)V gene-encoded residues only make a minimal contribution to the paratope.…”