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A SARS-CoV-2 variant elicits an antibody response with a shifted immunodominance hierarchy
Authors:Allison J Greaney  Tyler N Starr  Rachel T Eguia  Andrea N Loes  Khadija Khan  Farina Karim  Sandile Cele  John E Bowen  Jennifer K Logue  Davide Corti  David Veesler  Helen Y Chu  Alex Sigal  Jesse D Bloom
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.
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