Ancestral SARS-CoV-2 and Omicron BA.5-specific neutralizing antibody and T cell responses after Omicron bivalent booster vaccination in previously infected and infection-naive individuals

COVID-19 bivalent ancestral/Omicron mRNA booster vaccinations became available to boost and expand the immunity against SARS-CoV-2 Omicron infections. In a prospective cohort study including 59 healthcare workers, we assessed SARS-CoV-2 ancestral and Omicron BA.5-specific neutralizing antibody and T cell responses in previously infected and infection-naive individuals. Also, we assessed the effect of an ancestral/Omicron BA.1 bivalent mRNA booster vaccination on these immune responses. 10 months after previous monovalent mRNA vaccinations, ancestral SARS-CoV-2 S1-specific T cell and anti-RBD IgG responses remained detectable in most individuals and a previous SARS-CoV-2 infection was associated with increased T cell responses. T cell responses, anti-RBD IgG, and Omicron BA.5 neutralization activity increased after receiving an ancestral/Omicron BA.1 bivalent booster mRNA vaccination. An Omicron BA.5 infection in addition to bivalent vaccination led to a higher ratio of Omicron BA.5 to ancestral strain neutralization activity compared to bivalent vaccination without a recent SARS-CoV-2 infection. In conclusion, SARS-CoV-2 T cell and antibody responses persist for up to 10 months after a monovalent booster mRNA vaccination. An ancestral/Omicron BA.1 bivalent booster mRNA vaccination increases these immune responses and also induces Omicron BA.5 cross-neutralization antibody activity. Finally, our data indicate that hybrid immunity is associated with improved preservation of T cell immunity.