Repeated Omicron infection dampens immune imprinting from vaccination and induces broad neutralizing profiles against other Omicron sub-variants

Abstract

Abstract Protection from boosting with updated SARS-CoV-2 vaccines containing emerging Omicron sub-variants like BA.1 or BA.5 was not satisfying, especially the neutralizing ability against the newly emerged BQ and XBB related variants. Similar with influenza virus, antigenic drift is highly relevant to SARS-CoV-2 evolution, and immune imprinting may limit the performance of updated vaccines. In this study, we investigated whether repeated infection with Omicron variant could reduce the immune imprinting. A total of 194 participants with different status of vaccination (unvaccinated, regular vaccination and booster vaccination) confirmed for first infection and re-infection with BA.5, BF.7 and XBB variants were enrolled, and the neutralizing profiles against wild type (WT) SARS-CoV-2 and Omicron sub-variants were analyzed. The results showed that neutralizing potency against the corresponding infected variant is significantly hampered along with the doses of vaccination during first infection. However, for the participants with first infection of BA.5/BF.7 variants and re-infection of XBB variant, immune imprinting was obviously alleviated, indicated as significantly increased ratio of the corresponding infected variant/WT ID50 titers and higher percentage of samples with high neutralizing activities (ID50 > 500) against BA.5, BF.7 and XBB variants. Moreover, repeated Omicron infection could induce strong neutralizing potency with broad neutralizing profiles against a series of other Omicron sub-variants including the newly emerged EG.5.1 variant, both in the vaccine naïve and vaccine experienced individuals. In conclusion, our results provide useful information for the antigen selection and vaccination strategies, and indicated that repeated boosting vaccination with Omicron based vaccines especially the XBB sub-variant without the WT spike protein might achieve broad and efficient antibody responses against Omicron variant.