The trajectory of CD4+ T cell responses to mRNA vaccines in older individuals NatureAging KyotoU_News mRNA COVID19 coronavirus covid RNA cell Tcell aging agingresearch
By Neha MathurJan 16 2023Reviewed by Danielle Ellis, B.Sc. In a recent study published in Nature Aging, researchers investigated how age-related T-cell defects impacted the effectiveness of messenger ribonucleic acid -based coronavirus disease 2019 vaccines.
About the study In the present study, researchers recruited 216 severe acute respiratory syndrome coronavirus 2 -naïve Japanese participants comprising adults and older adults aged less than and above 65 years, respectively. They all had received a primary vaccination series of BNT162b2 within an average of 21 days.
The effect of preexisting T cells on immune responses elicited following vaccination was limited. Before COVID-19 vaccination, CD4+ T cells also comprised cross-reactive T cell populations. Their frequency had a weak correlation post-first vaccination in older adults. However, the same was not the case after the second dose, at three months, or peak antibody titers.
Importantly, studies have shown a poor response to the first vaccine dose in patients with solid cancer and subsequent lower antibody responses. Perhaps, the delayed development of TFH cells and subsequently neutralizing antibodies correlated with fatal COVID-19 in older adults. Together, these findings point to the significance of CD4+ T cell responses to the first vaccine dose in improving the effects of vaccination and that older individuals had a defective process.
Furthermore, the researchers noted accelerated cell death of S-specific T cells in older adults, indicated by their early contraction. Notably, programmed death-1 expression in S-specific TH1 cells was higher in older adults at the maximal response, indicating its inhibitory role. It is unknown whether the enhanced PD-1 expression levels represented higher activation or exhaustion in older adults.
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