Age and primary vaccination schedule impact humoral and cellular immunity with an inactivated SARS-CoV-2 vaccine

Despite widespread COVID-19 vaccination, questions remain about vaccine safety and immunogenicity in vulnerable populations, such as older adults. We evaluated the safety and immunogenicity of four doses of CoronaVac in adults above and below 60 who received the first two doses in two different schedules (0-14 and 0-28 days apart). While CoronaVac demonstrated excellent safety across age groups, older adults showed reduced reactogenicity. In the 0-28 schedule, both age groups exhibited similar frequencies of SARS-CoV-2-specific CD4(+) and CD8(+) T cells, though memory T cell distribution patterns differed. Notably, adults over 60 showed diminished virus-neutralizing antibody responses compared to younger participants. The 0-14 schedule produced equivalent cellular and neutralizing antibody responses between age groups, albeit at lower levels than the 0-28 schedule. Our data indicate that primary vaccination schedules can influence the humoral immune responses and memory T cell distribution between age groups.