Antibodies From SARS-CoV-2 Beta Variant Infection Target a Different Region of the Spike Protein

Publication CommentaryNovember 18, 2022

Dr. Jesse Bloom’s research group, including Greaney, Eguia, and Loes from the Fred Hutchinson Cancer Research Center, part of the University of Pennsylvania Centers of Excellence for Influenza Research and Response (Penn-CEIRR), provided important insight into differences in SARS-CoV-2 antibody repertoires. Specifically, the researchers compared antibodies from a person infected with SARS-CoV-2 variants that circulated in early 2020 to those with antibodies against the Beta variant (B.1.351). As SARS-CoV-2 evolves and the viral regions the immune system target change, the dominant immune landscape will also drift. In this case, researchers found the regions of the virus that the majority of antibodies target change as novel variants arise.

Vials of South African strains of SARS-CoV-2.

Since early 2020, six SARS-CoV-2 variants have been designated as variants of concern in the United States. The Beta variant emerged in South Africa in mid-2020 and became the dominant lineage in the country by the end of 2020. The variant’s prevalence elsewhere was more limited due to the emergence of the highly transmissible Delta variant. The Beta variant was designated as a variant of concern at the end of December 2020 due to concerns over its ability to evade immunity driven by previous infection or vaccination.  

The Penn-CEIRR researchers investigated whether the most common viral region that antibodies target and bind to differ between early 2020 SARS-CoV-2 infections and infections with the Beta variant. Plasma samples from individuals infected during the second wave of COVID-19 in South Africa, when the Beta variant accounted for nearly all infections within the country, were compared to plasma samples previously collected in Washington State at the start of the pandemic. The researchers found that antibodies elicited from infection with either variant are driven by mutations within the receptor-binding domain, a region of the SARS-CoV-2 spike protein that enables entry into host cells. The antibodies produced after infection with the Beta variant, however, were more like an epitope class that differed from the epitope class early variant antibodies targeted. The findings provide insight into how SARS-CoV-2 exposure may influence a person’s susceptibility to future variants. Similar studies will only become more important as the virus continues to evolve, and the population continues to be infected with a diverse array of viral mutants.

Greaney AJ, et al. (2022) A SARS-CoV-2 variant elicits an antibody response with a shifted immunodominance hierarchy. PLoS Pathog 18(2): e1010248.