Introduction
Shortly after the first detection of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron (B.1.1.529) variant in November 2021, Omicron became the global dominant variant that sustains the ongoing coronavirus disease 2019 (COVID-19) pandemic.1,2 Omicron infections are mainly restricted to the upper respiratory tract and are thus generally associated with mild disease.3,4 However, Omicron infections may still result in severe disease in immunocompromized patients or those with pre-existing comorbidities, which substantially contributes to hospitalization rates and general disease burden.5,6
Several observational studies reported a high incidence of Omicron vaccine-breakthrough infections and reinfections.7,8These findings can be explained by the more than 30 substitutions in the spike protein, which make Omicron highly transmissible and very efficient at immune evasion.9,10 Moreover, these characteristics improved even further in each Omicron subvariant, including the previously dominant BA.1, BA.2, BA.4, and BA.5,1,10 and the most recent dominant subvariants XBB and XBB1.5.2,11
The continuing emergence of new Omicron subvariants and concerns about waning immunity have led to the development of bivalent booster vaccines. From September 2022, these bivalent vaccines, containing spike-encoding mRNA of both the ancestral strain and Omicron BA.1, were first administered. However, a limited number of studies explored the effects of these bivalent vaccinations and latest Omicron variant infections on both neutralizing antibody (nAb) and T cell responses. Therefore, we performed a prospective cohort study aimed to investigate the impact of an ancestral/Omicron BA.1 bivalent booster vaccination, a recent Omicron BA.5 infection, or a combination of these on ancestral and Omicron BA.5 specific T cell and nAbs responses.