Authors: Norihide Jo, Yu Hidaka, Osamu Kikuchi, Masaru Fukahori, Takeshi Sawada, Masahiko Aoki, Masaki Yamamoto, Miki Nagao, Satoshi Morita, Takako E. Nakajima, Manabu Muto, Yoko Hamazaki
Published: 2023-01-12
DOI: 10.1038/s43587-022-00343-4
Source: Full article
AbstractWhether age-associated defects in T cells impact the immunogenicity and reactogenicity of mRNA vaccines remains unclear. Using a vaccinated cohort (nā=ā216), we demonstrated that older adults (aged ā„65 years) had fewer vaccine-induced spike-specific CD4+ T cells including CXCR3+ circulating follicular helper T cells and the TH1 subset of helper T cells after the first dose, which correlated with their lower peak IgG levels and fewer systemic adverse effects after the second dose, compared with younger adults. Moreover, spike-specific TH1 cells in older adults expressed higher levels of programmed cell death protein 1, a negative regulator of T cell activation, which was associated with low spike-specific CD8+ T cell responses. Thus, an inefficient CD4+ T cell response after the first dose may reduce the production of helper T cytokines, even after the second dose, thereby lowering humoral and cellular immunity and reducing systemic reactogenicity. Therefore, enhancing CD4+ T cell response following the first dose is key to improving vaccine efficacy in older adults.