Tu96 - Epitope Profiling of COVID-19 Convalescent Plasma and Vaccine Elicited Antibodies

Background: Immune responses to SARS-CoV-2 following infection or vaccination are highly variable, which may contribute to reinfection or vaccine breakthrough infections. A comprehensive evaluation of antibody binding to SARS-CoV-2 (CoV2) and endemic human coronaviruses (HCoVs) may identify individuals at increased risk for future infection and highlight the role of coronavirus cross-reactivity in antibody response potency.

Methods: We generated all possible 56 amino acid peptide epitopes that could be produced by in-frame or out-of-frame translation of the CoV2 or HCoV genomes. We then quantified antibody reactivity to these epitopes via phage immunoprecipitation sequencing (PhIP-seq) of serum antibodies from 38 COVID-19 recovered individuals, 21 vaccinated individuals, and 13 vaccinated individuals who subsequently developed breakthrough infections. We additionally performed coronavirus focused PhIP-seq on 126 potential COVID-19 convalescent plasma (CCP) donations with known SARS-CoV-2 neutralization capacity.

Results: CoV2 reactive antibodies from vaccinated and infected individuals rarely, if ever, targeted out-of-frame translation products. Spike epitope reactivities post-vaccination were well correlated to those following infection. Antibody reactivity to an immunodominant region of HCoV HKU1 spike occurred with significantly greater frequency in vaccinated individuals who went on to experience breakthrough infections compared to vaccinated individuals who did not become infected. Furthermore, potential CCP donations with antibody reactivity to this HKU1 epitope had relatively diminished SARS-CoV-2 neutralizing.

Conclusions: Coronavirus epitope profiling revealed interplay between endemic coronavirus antibody reactivity and the CoV2 antibody response, supporting a role for exposures to HCoVs in shaping the CoV2 immune response at the epitope level.