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The adaptive immunity against SARS-CoV-2 prototype strain and Omicron sublineages induced by BA.1 breakthrough infection in vaccinees of inactivated COVID-19 vaccines have not been well characterized. Here, we report that BA.1 breakthrough infection induced mucosal sIgA and resulted in higher IgG titers against SARS-CoV-2 prototype strain and Omicron sublineages in vaccinees than in vaccine naïve-infected individuals. BA.1 breakthrough infection also boosted antibody-dependent cellular cytotoxicity and antibody-dependent cellular phagocytosis to SARS-CoV-2 prototype strain and BA.1, BA.1.1, BA.2, BA.2.12.1, and BA.2.75 but not to BA.4/5 and induced neutralizing antibody (NAb) responses against the prototype strain and BA.1, BA.1.1, BA.2, BA.2.12.1, BA.2.75, and BA.4/5 but not against BF.7, BQ.1, and XBB. In total, BA.1 breakthrough infection individuals produced less extensive sIgA, plasma IgG and NAb responses against Omicron sublineages compared with those against the prototype strain. Further, BA.1 breakthrough infection induced recall B cell response to the prototype strain and the Omicron variant, primarily targeting memory B cells producing conserved epitopes. Memory T cell responses against Omicron is largely preserved. Individuals with vaccine booster did not induce more beneficial immune responses to Omicron sublineages upon BA.1 breakthrough infection than those with primary vaccine doses only. The breakthrough infection individuals produced stronger antibody and T cell responses than those of inactivated vaccine-healthy individuals. These data have important implications for understanding the vaccine effectiveness and adapted immunity to breakthrough infection in individuals fully immunized with inactivated vaccines. The Omicron sublineages, especially for those emerged after BA.4/5 strain, evade the NAb responses induced by BA.1 breakthrough infection. It is urgent to optimize the vaccine immunogen design and formulations to SARS-CoV-2 variants.

Original publication




Journal article


Emerg Microbes Infect

Publication Date



Omicron sublineages, SARS-CoV-2, breakthrough infection, cellular immune responses, humoral immune responses