Deep mutational scanning shows that the mRNA-1273 RBD-binding antibody response is less affected by single viral mutations than the infection response. Binding Breadth Antibody responses elicited by natural infection or vaccination against the same target are known to differ. However, the extent to which antibody responses to the SARS-CoV-2 receptor binding domain (RBD) differ between vaccination and infection has not been fully characterized. Here, Greaney et al. demonstrated that neutralizing antibodies elicited by immunization with the Moderna mRNA-1273 vaccine were more focused to the RBD than those elicited by natural infection. However, vaccination-elicited antibodies targeted a broader range of epitopes within the RBD than infection-elicited antibodies. These findings demonstrate that the type of exposure, including different types of vaccines or infection, can influence the antibody response to SARS-CoV-2. The emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants with mutations in key antibody epitopes has raised concerns that antigenic evolution could erode adaptive immunity elicited by prior infection or vaccination. The susceptibility of immunity to viral evolution is shaped in part by the breadth of epitopes targeted by antibodies elicited by vaccination or natural infection. To investigate how human antibody responses to vaccines are influenced by viral mutations, we used deep mutational scanning to compare the specificity of polyclonal antibodies elicited by either two doses of the mRNA-1273 COVID-19 vaccine or natural infection with SARS-CoV-2. The neutralizing activity of vaccine-elicited antibodies was more targeted to the receptor-binding domain (RBD) of the SARS-CoV-2 spike protein compared to antibodies elicited by natural infection. However, within the RBD, binding of vaccine-elicited antibodies was more broadly distributed across epitopes compared to infection-elicited antibodies. This greater binding breadth means that single RBD mutations have less impact on neutralization by vaccine sera compared to convalescent sera. Therefore, antibody immunity acquired by natural infection or different modes of vaccination may have a differing susceptibility to erosion by SARS-CoV-2 evolution.
【초록키워드】 neutralizing antibody, antibodies, SARS-CoV-2, Adaptive immunity, Vaccine, coronavirus, vaccination, Mutation, adaptive, Immunity, Neutralizing antibodies, antibody, mRNA-1273, neutralization, susceptibility, Antibody Response, variant, Infection, severe acute respiratory syndrome Coronavirus, immunization, variants, Spike protein, Receptor binding domain, specificity, Epitopes, Neutralizing activity, Antibody responses, Viral, Receptor-binding domain, RBD, viral evolution, mRNA, sera, SARS-CoV-2 spike protein, SARS-CoV-2 evolution, polyclonal antibodies, respiratory, natural infection, epitope, antibody epitope, Viral mutations, convalescent sera, binding, breadth, dose, mRNA-1273 COVID-19 vaccine, polyclonal antibody, acute respiratory syndrome, human antibody response, acute respiratory syndrome coronavirus, acute respiratory syndrome coronavirus 2, antigenic evolution, antibody immunity, antibody epitopes, viral mutation, erosion, Moderna mRNA-1273 vaccine, RBD mutation, deep, greater, affected, raised, characterized, less, demonstrated, the RBD, the receptor-binding domain, elicited, the antibody response, RBD-binding antibody, the SARS-CoV-2, 【제목키워드】 vaccination, mRNA-1273, SARS-COV-2 infection, Receptor binding domain, elicited,