ABSTRACT
Background: The inactivated whole-virion vaccine, CoronaVac, is one of the most widely used coronavirus disease 2019 (COVID-19) vaccines worldwide. There is a paucity of data indicating the durability of the immune response and the impact of immune imprinting induced by CoronaVac upon Omicron breakthrough infection. Methods: In this prospective cohort study, 41 recipients of triple-dose CoronaVac and 14 unvaccinated individuals were recruited. We comprehensively profiled adaptive immune parameters in both groups, including spike-specific immunoglobulin (Ig) G and IgA titers, neutralizing activity, B cells, follicular helper T (Tfh) cells, CD4+ and CD8+ T cells, and their memory subpopulations at 12 months after the third booster dose and at 4 weeks and 20 weeks after Omicron BA.5 infection. Results: Twelve months after the third CoronaVac vaccination, spike-specific antibody and cellular responses were detectable in most vaccinated individuals. BA.5 infection significantly augmented the magnitude, cross-reactivity and durability of serum neutralization activities, Fc-mediated phagocytosis, and nasal spike-specific IgA responses, memory B cells, activated Tfh cells memory CD4+ T cells, and memory CD8+ T cells for both the ancestral strain and Omicron subvariants, compared to unvaccinated individuals. Notably, the increase in BA.5-specific immunity after breakthrough infection was consistently higher than for the ancestral strain, suggesting no evidence of immune imprinting. Immune landscape analyses showed vaccinated individuals have better synchronization of multiple immune components than unvaccinated individuals upon heterologous SARS-CoV-2 infection. Conclusion: Our data provides detailed insight into the protective role of inactivated COVID-19 vaccine in shaping humoral and cellular immune responses to heterologous Omicron infection.