Systemic immune profiling of Omicron-infected subjects inoculated with different doses of inactivated virus vaccine.

SARS-CoV-2 primary strain-based vaccination exerts a protective effect against Omicron variants-initiated infection, symptom occurrence, and disease severity in a booster-dependent manner. Yet, the underlying mechanisms remain unclear. During the 2022 Omicron outbreak in Shanghai, we enrolled 122 infected adults and 50 uninfected controls who had been unvaccinated or vaccinated with two or three doses of COVID-19 inactive vaccines and performed integrative analysis of 41-plex CyTOF, RNA-seq, and Olink on their peripheral blood samples. The frequencies of HLA-DRhi classical monocytes, non-classical monocytes, and Th1-like Tem tended to increase, whereas the frequency of Treg was reduced by booster vaccine, and they influenced symptom occurrence in a vaccine dose-dependent manner. Intercorrelation and mechanistic analysis suggested that the booster vaccination induced monocytic training, which would prime monocytic activation and maturation rather than differentiating into myeloid-derived suppressive cells upon Omicron infections. Overall, our study provides insights into how booster vaccination elaborates protective immunity across SARS-CoV-2 variants. [Display omitted] • Vaccination histories with inactivated virus influence Omicron-triggered immunity • Innate immunity and Th1 cells are primed by three doses of inactivated virus vaccine • Innate immunity or T cell activation state associates with asymptomatic infection • Monocytic training by inactive vaccine prepares host to cope with Omicron challenge Analysis of immune responses induced by inactivated virus vaccines against SARS-CoV-2, with and without Omicron variant infection, provides insight into the relative effects of single and double boosting for the large population that received this form of COVID-19 vaccine. [ABSTRACT FROM AUTHOR]

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