This study investigated the impact of different SARS-CoV-2 vaccination and infection histories on the immune response to Omicron subvariants. Omicron breakthrough infection, regardless of prior mRNA or inactivated vaccination, resulted in higher neutralizing antibody levels and stronger T-cell responses compared to Delta breakthrough infection after inactivated vaccination. Different vaccination-infection patterns influenced T-cell differentiation, with mRNA vaccination followed by Omicron infection showing higher levels of specific CD4⁺ T cells. Breakthrough infection groups exhibited enhanced T-cell proliferation and multi-functionality. The study suggests that Omicron's higher immunogenicity may have contributed to the replacement of the Delta variant. The findings advance understanding of immune imprinting and inform future vaccination strategies.
