Omicron breakthrough infections in wild-type SARS-CoV-2 vaccinees elicit high levels of neutralizing antibodies against pangolin coronavirus GX_P2V

Omicron BF.7 became the predominant SARS-CoV-2 variant in Beijing after the adjustment of COVID-19 response strategies in December 2022. The ability of antibodies elicited by BF.7 infection to cross-react with SARS-CoV-2-like viruses is unknown. This study aimed to investigate the cross-reactive neutralizing antibodies against SARS-CoV-2-related pangolin coronavirus GX_P2V in sera from vaccinated and/or SARS-CoV-2 infected individuals. All vaccinated individuals who recovered from Omicron BF.7 breakthrough infections exhibited substantially higher levels of neutralizing antibodies against GX_P2V among collected subject populations (geometric mean titer [GMT] = 362). Uninfected individuals who received four-mixed-dose vaccines also demonstrated higher levels of neutralizing antibodies (GMT = 44) against GX_P2V than those who received two- or three-dose vaccines and those who recovered from wild type SARS-CoV-2. This finding highlights the significance of prior and hybrid booster vaccinations with wild-type SARS-CoV-2 vaccines in generating potent cross-protective immunity against future spillovers of SARS-CoV-2-like viruses.