Antigenic Imprinting and Immune Response Dynamics: Neutralization Against Emerging SARS-CoV-2 Omicron Variants Following Breakthrough Infections.

The recently mutated Omicron variant of SARS-CoV-2 exhibits extremely high infectivity and strong evolution and immune escape capabilities. Given the unique epidemic prevention policies of China, we collected 16 sets of sera from convalescent individuals (n = 308) with breakthrough infections who had received different immunization regimens and from healthy people over the subsequent year after epidemic control ceased in China on 7 December 2022. We assessed the susceptibility of the serum to the prototype, Omicron BA.5.2, Omicron XBB.1.5, and Omicron JN.1.5 subvariants at 3-, 5-, 8- and 11-months postinfection. The results demonstrated that two booster immunizations did not enhance the immune response, indicating that breakthrough Omicron infection does not effectively increase immunity against other Omicron subvariants. Rather, the breakthrough infection might even weaken the immune response to Omicron subvariants due to antigenic imprinting, highlighting the necessity of optimizing vaccination strategies and adjusting epidemic prevention measures to the situation.