Adjuvant-dependent protection of SARS-CoV-2 spike vaccines: comparative immunogenicity of human-applicable formulations

Persistent viral evolution, rapid waning of vaccine-induced immunity, and the heightened vulnerability of elderly populations remain major challenges for COVID-19 vaccination strategies. In this study, we systematically assessed immune responses elicited by the ancestral spike protein formulated with four distinct adjuvants in mouse models. We demonstrate that an optimized adjuvant formulation markedly enhances the magnitude and breadth of antibody responses, potentiates T-cell immunity, and rapidly induces sustained peak antibody titers against both homologous virus and Omicron variants. Vaccine-induced antibody responses were significantly attenuated in aged mice, and furthermore, both the protective efficacy of antibodies and inflammatory cytokine responses upon viral challenge were impaired in aged animals. These results provide compelling evidence that rational adjuvant selection is critical for enabling recombinant vaccines to achieve rapid-onset, broad, and durable immune protection. Furthermore, our study offers new mechanistic insights into the reduced vaccine efficacy observed in the elderly.