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.

Coronavirus disease-2019 (COVID-19) bivalent ancestral/Omicron messenger RNA (mRNA) booster vaccinations became available to boost and expand the immunity against severe acute respiratory syndrome coronavirus 2 (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 no bivalent vaccination and no 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.