Impact of pre-existing immunity on humoral and cellular responses to CoronaVac in SARS-CoV-2 variants: A focus on common human Coronaviruses.

Background: The global COVID-19 pandemic, caused by SARS-CoV-2, has highlighted the importance of understanding immune responses elicited by vaccines.

Objective: This study evaluated antibody and T cell responses to the inactivated CoronaVac vaccine, as well as the role of pre-existing immunity to common human coronaviruses (HCoVs) in shaping vaccine-induced immunity.

Methods: We enrolled 64 participants (17 males and 47 females) and measured IgG levels against HCoVs before and after vaccination. T cell responses were analysed by stimulating peripheral blood mononuclear cells (PBMCs) with wild-type, Delta, and Omicron spike peptides.

Results: We found pre-existing antibodies against HCoV-229E, HCoV-HKU1, HCoV-NL63, and HCoV-OC43 were present before vaccination. Notably, a positive correlation was observed between pre-existing antibodies to HCoV-229E and HCoV-HKU1 and anti-RBD IgG levels post-vaccination. Pre-existing CD4+ T cell responses were observed for the wild-type strain before vaccination, with a significant reduction in IFN-γ secretion after Delta re-stimulation and partial restoration after Omicron re-stimulation. IL-4 production by CD4+ T cells was significantly reduced upon re-stimulation with Delta and Omicron compared to wild-type. CD8+ T cells again showed a reduction of IL-4 production after Delta re-stimulation compared to the original strain.

Conclusions: This work demonstrate that CoronaVac induces robust humoral and cellular immune responses, though variant-specific responses vary. Pre-existing immunity to certain HCoVs may influence vaccine-induced antibody responses, underscoring the importance of monitoring immunity to emerging SARS-CoV-2 variants and informing future vaccine design.