Cross-reactive antibodies elicited to conserved epitopes on SARS-CoV-2 spike protein after infection and vaccination.

SARS-CoV-2 is a novel betacoronavirus that caused 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 could prime immune responses in humans. Thus, SARS-CoV-2 conserved epitopes elicit cross-reactive immune responses to both related coronaviruses and host bacteria that could serve as future targets for broad coronavirus therapeutics and vaccines.

Vaccination After SARS-CoV-2 Infection Increased Antibody Avidity Against the Omicron Variant Compared to Vaccination Alone.

The SARS-CoV-2 Omicron variant has caused infections among individuals vaccinated or with prior COVID-19, suggesting immune escape. Here, we showed a decrease in binding and surrogate neutralizing antibody responses to the Omicron variant after 2 doses of the Pfizer COVID-19 mRNA vaccine. Individuals recovered from infection before vaccination had higher antibody levels and avidity to the Omicron variant compared to individuals vaccinated without infection. This suggested that COVID-19 infection before vaccination elicited a higher magnitude and affinity antibody response to the Omicron variant, and repeated exposure through infection or vaccine may be required to improve immunity to emerging SARS-CoV-2 variants.