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.