Immunological characteristics of inactivated vaccines after vaccination and short-term concentrated BA.4/5 exposure: A prospective cohort study in Henan, China.

In December 2022, a large population in China was simultaneously exposed to the SARS-CoV-2 Omicron BA.4/5 variant after prior inactivated vaccination, creating a unique opportunity to assess post-vaccination immune responses. This prospective cohort study enrolled 1292 inactivated vaccine recipients and longitudinally evaluated their humoral and cellular immunity.Anti-SARS-CoV-2 IgG titres and virus-specific T-cell responses were assessed at 2, 4, 8, and 24 weeks post-vaccination using ELISpot and flow cytometry. During the BA.4/5 outbreak, 1043 participants were re-evaluated, with 52.2 % experiencing breakthrough infections confirmed by RT-PCR or antigen testing. Natural infection elicited significantly higher peak IgG titres and IFN-γ+ T-cell responses than vaccination alone, with a faster time to peak (2 vs. 4 weeks). Patients with mild/moderate disease mounted stronger and earlier IgG and T-cell responses than severe/critical cases. Lymphocyte subset analysis revealed greater depletion of CD4+, CD8+, and NK cells in severe cases, with delayed and incomplete recovery. These results indicate that while pre-existing immunity from inactivated vaccines does not fully prevent infection, it modulates immune kinetics and clinical outcomes. A rapid and coordinated immune response appears critical in mitigating severity. This study provides important insights into the interaction between inactivated vaccine-induced immunity and natural Omicron infection, reinforcing the importance of booster vaccination and immune surveillance.