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J Med Virol . Repeated Omicron Infections Overcome T Cell Immune Imprinting to Original SARS-CoV-2

tetano

Editor, Senior Moderator
J Med Virol


. 2025 Feb;97(2):e70264.
doi: 10.1002/jmv.70264. Repeated Omicron Infections Overcome T Cell Immune Imprinting to Original SARS-CoV-2

Yunfei Li[SUP] 1 [/SUP], Junyao Lu[SUP] 2 [/SUP], Liheng He[SUP] 1 [/SUP], Chengxin Jiang[SUP] 1 [/SUP], Yujie Bao[SUP] 2 [/SUP], Ping Ji[SUP] 1 [/SUP], Jie Xu[SUP] 2 3 [/SUP], Yingying Chen[SUP] 1 4 [/SUP], Ying Wang[SUP] 1 3 4 5 [/SUP]



Affiliations
Abstract

Multiple studies demonstrate the existence of attenuated neutralizing activity to the Omicron variants in the original SARS-CoV-2 strain vaccinated population undergoing breakthrough infection, which reflects a phenomenon of immune imprinting in humoral immunity. Herein, through designing spike protein peptide pools from four Omicron subvariants and the wild type (WT) counterpart, we intended to determine antiviral T cell immunoreactivity in Omicron-infected COVID-19 patients with or without previous vaccination. We have demonstrated that IFN-γ producing cells against the Omicron subvariants-derived peptide pools were significantly less than those against WT counterpart peptide pools in the Omicron BA.5/BA.7 infected patients receiving original inactivated SARS-CoV-2 vaccination whereas comparable in the unvaccinated group. Notably, reinfection with the Omicron subvariants restored viral-specific T cell immunity to the infected Omicron strains in vaccinated individuals. Therefore, similar to humoral immunity vaccination with the original SARS-CoV-2 strain-derived vaccines induces T cell immune imprinting when undergoing Omicron subvariants breakthrough infection. Since reinfection of Omicron subvariants can restore T cell immunoreactivity to the infected strains, it is necessary to design multivalent immunogens for vaccine development to overcome both B cell and T cell immune imprinting against SARS-CoV-2 and other highly mutant pathogens.

Keywords: COVID‐19 vaccines; Omicron reinfection; S protein‐specific IFN‐γ releasing level; SARS‐CoV‐2.

 
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