Abstract
Many SARS-CoV-2 variants have mutations at key sites targeted by antibodies. However, it is unknown if antibodies elicited by infection with these variants target the same or different regions of the viral spike as antibodies elicited by earlier viral isolates. Here we compare the specificities of polyclonal antibodies produced by humans infected with early 2020 isolates versus the B.1.351 variant of concern (also known as Beta or 20H/501Y.V2), which contains mutations in multiple key spike epitopes. The serum neutralizing activity of antibodies elicited by infection with both early 2020 viruses and B.1.351 is heavily focused on the spike receptor-binding domain (RBD). However, within the RBD, B.1.351-elicited antibodies are more focused on the "class 3" epitope spanning sites 443 to 452, and neutralization by these antibodies is notably less affected by mutations at residue 484. Our results show that SARS-CoV-2 variants can elicit polyclonal antibodies with different immunodominance hierarchies.
Highlights
Over the past year, SARS-CoV-2 viral variants have emerged with mutations that alter the antigenicity of spike and erode neutralization of the virus by infection- and vaccine-elicited polyclonal antibodies [1,2,3,4,5,6,7,8,9,10,11,12,13]
SARS-CoV-2 has circulated among humans for approximately two years, and mutations in emerging variants can erode immunity elicited by prior infection or vaccination
If a similar phenomenon occurs for SARS-CoV-2, the sites of important antigenic mutations will change over time
Summary
SARS-CoV-2 viral variants have emerged with mutations that alter the antigenicity of spike and erode neutralization of the virus by infection- and vaccine-elicited polyclonal antibodies [1,2,3,4,5,6,7,8,9,10,11,12,13]. If a similar phenomenon occurs for SARS-CoV-2, the sites of important antigenic mutations will change over time. We address this question by combining serology and deep mutational scanning to compare the specificity of the polyclonal antibody response elicited by infection with early 2020 viruses versus the B.1.351 variant ( referred to as Beta or 20H/501Y.V2). Within the RBD, B.1.351-elicited sera is relatively more targeted to the class 3 epitope (in the classification scheme of [23]) and relatively less targeted to the class 1 and 2 epitopes
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