Identification of conserved coronavirus epitopes targeted by antibodies after SARS-CoV-2 infection or vaccination

Abstract SARS-CoV-2 is a novel betacoronavirus that causes coronavirus disease 2019 and has resulted in millions of deaths worldwide. Novel coronavirus infections in humans have steadily become more common. Understanding antibody responses to SARS-CoV-2, and identifying conserved, cross-reactive epitopes among coronavirus strains could inform the design of vaccines and therapeutics with broad application. Here, we determined that individuals with previous SARS-CoV-2 infection or vaccinated with the Pfizer-BioNTech BNT162b2 vaccine produced antibody responses that cross-reacted with related betacoronaviruses. Moreover, we designed a peptide-conjugate vaccine with a conserved SARS-CoV-2 S2 spike epitope, immunized mice and determined cross-reactive antibody binding to SARS-CoV-2 and other related coronaviruses. This conserved spike epitope also shared sequence homology to proteins in commensal gut microbiota and antibodies targeting this region reacted with proteins in human fecal protein extracts. This indicated that the composition of the gut microbiota could prime immune responses in humans. Thus, SARS-CoV-2 conserved epitopes elicited cross-reactive immune responses to both related coronaviruses and host bacteria that could serve as future targets for broad coronavirus therapeutics and vaccines. This work was supported through internal institutional funds from Children’s Mercy Research Institute and Children’s Mercy Kansas City.