Systemic immune profiling of Omicron-infected subjects with differential vaccination history

SARS-CoV-2 primary strain-based vaccination exerts protective effect against Omicron variants-initiated breakthrough infection and disease severity in a booster-dependent manner. Yet, the underlying mechanisms remain unclear. During the 2022 Omicron outbreak in Shanghai, we enrolled122 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.
Conclusion:
The frequencies of HLA-DRhi-classical monocytes, non-classical monocytes, pDCs and Th1-like Tem were increased while the frequency of Treg was reduced in 3-dose vaccinated group compared with 2-dose vaccinated or unvaccinated group. Intercorrelation and mechanistic analysis suggested that the booster vaccination induced a monocytic training which would prime monocytic activation and maturation rather than differentiating into myeloid-derived suppressive cells to restrain pathogenic Treg expansion upon Omicron infections. Our study provides insights into how booster vaccination elaborates protective immunity across SARS-CoV-2 variants.