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Front Immunol
. 2024 Dec 9:15:1455334.
doi: 10.3389/fimmu.2024.1455334. eCollection 2024. Booster COVID-19 mRNA vaccination ameliorates impaired B-cell but not T-cell responses in older adults
Kohei Kometani 1 , Takaaki Yorimitsu 1 2 , Norihide Jo 1 3 , Erina Yamaguchi 1 , Osamu Kikuchi 4 5 6 , Masaru Fukahori 7 8 , Takeshi Sawada 7 8 , Yoshitaka Tsujimoto 1 9 , Ayana Sunami 1 10 , Mengqian Li 1 , Takeshi Ito 1 , Yann Pretemer 1 , Yuxian Gao 1 10 , Yu Hidaka 11 , Masaki Yamamoto 12 , Natsuko Kaku 13 14 , Yu Nakagama 13 14 , Yasutoshi Kido 13 14 , Alba Grifoni 15 , Alessandro Sette 15 16 , Miki Nagao 12 , Satoshi Morita 11 , Takako E Nakajima 7 8 , Manabu Muto 4 5 8 , Yoko Hamazaki 1 10 17
Affiliations
Age-associated differences in the effect of repetitive vaccination, particularly on memory T-cell and B-cell responses, remain unclear. While older adults (aged ≥65 years) exhibited enhanced IgG responses following COVID-19 mRNA booster vaccination, they produced fewer spike-specific circulating follicular helper T cells-1 than younger adults. Similarly, the cytotoxic CD8+ T-cell response remained diminished with reduced PD-1 expression even after booster vaccination compared with that in younger adults, suggesting impaired memory T-cell activation in older adults. In contrast, although B-cell responses in older adults were weaker than those in younger adults in the primary response, the responses were significantly enhanced upon booster vaccination, reaching levels comparable with that observed in younger adults. Therefore, while booster vaccination ameliorates impaired humoral immunity in older adults by efficiently stimulating memory B-cell responses, it may less effectively enhance T-cell-mediated cellular immunity. Our study provides insights for the development of effective therapeutic and vaccine strategies for the most vulnerable older population.
Keywords: COVID-19 article type: original research article; booster vaccination; cTfh; immune aging; immunological memory; mRNA vaccine; memory B cells; memory T cells.
. 2024 Dec 9:15:1455334.
doi: 10.3389/fimmu.2024.1455334. eCollection 2024. Booster COVID-19 mRNA vaccination ameliorates impaired B-cell but not T-cell responses in older adults
Kohei Kometani 1 , Takaaki Yorimitsu 1 2 , Norihide Jo 1 3 , Erina Yamaguchi 1 , Osamu Kikuchi 4 5 6 , Masaru Fukahori 7 8 , Takeshi Sawada 7 8 , Yoshitaka Tsujimoto 1 9 , Ayana Sunami 1 10 , Mengqian Li 1 , Takeshi Ito 1 , Yann Pretemer 1 , Yuxian Gao 1 10 , Yu Hidaka 11 , Masaki Yamamoto 12 , Natsuko Kaku 13 14 , Yu Nakagama 13 14 , Yasutoshi Kido 13 14 , Alba Grifoni 15 , Alessandro Sette 15 16 , Miki Nagao 12 , Satoshi Morita 11 , Takako E Nakajima 7 8 , Manabu Muto 4 5 8 , Yoko Hamazaki 1 10 17
Affiliations
- PMID: 39717779
- PMCID: PMC11663736
- DOI: 10.3389/fimmu.2024.1455334
Age-associated differences in the effect of repetitive vaccination, particularly on memory T-cell and B-cell responses, remain unclear. While older adults (aged ≥65 years) exhibited enhanced IgG responses following COVID-19 mRNA booster vaccination, they produced fewer spike-specific circulating follicular helper T cells-1 than younger adults. Similarly, the cytotoxic CD8+ T-cell response remained diminished with reduced PD-1 expression even after booster vaccination compared with that in younger adults, suggesting impaired memory T-cell activation in older adults. In contrast, although B-cell responses in older adults were weaker than those in younger adults in the primary response, the responses were significantly enhanced upon booster vaccination, reaching levels comparable with that observed in younger adults. Therefore, while booster vaccination ameliorates impaired humoral immunity in older adults by efficiently stimulating memory B-cell responses, it may less effectively enhance T-cell-mediated cellular immunity. Our study provides insights for the development of effective therapeutic and vaccine strategies for the most vulnerable older population.
Keywords: COVID-19 article type: original research article; booster vaccination; cTfh; immune aging; immunological memory; mRNA vaccine; memory B cells; memory T cells.