Impaired CD4⁺ T cell response in older adults is associated with reduced immunogenicity and reactogenicity of mRNA COVID-19 vaccination

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  • Jo, Norihide
    Department of Life Science Frontiers, Center for iPS Cell Research and Application (CiRA), Kyoto University; Alliance Laboratory for Advanced Medical Research, Graduate school of Medicine, Kyoto University
  • Hidaka, Yu
    Department of Biomedical Statistics and Bioinformatics, Graduate School of Medicine, Kyoto University
  • Kikuchi, Osamu
    Department of Therapeutic Oncology, Graduate School of Medicine, Kyoto University; Clinical Bio-Resource Center, Kyoto University Hospital
  • Fukahori, Masaru
    Department of Early Clinical Development, Graduate school of Medicine, Kyoto University; Kyoto Innovation Center for Next Generation Clinical Trials and iPS Cell Therapy (Ki-CONNECT), Kyoto University Hospital
  • Sawada, Takeshi
    Department of Early Clinical Development, Graduate school of Medicine, Kyoto University; Kyoto Innovation Center for Next Generation Clinical Trials and iPS Cell Therapy (Ki-CONNECT), Kyoto University Hospital
  • Aoki, Masahiko
    Department of Early Clinical Development, Graduate school of Medicine, Kyoto University; Kyoto Innovation Center for Next Generation Clinical Trials and iPS Cell Therapy (Ki-CONNECT), Kyoto University Hospital
  • Yamamoto, Masaki
    Department of Clinical Laboratory Medicine, Graduate School of Medicine, Kyoto University
  • Nagao, Miki
    Department of Clinical Laboratory Medicine, Graduate School of Medicine, Kyoto University
  • Morita, Satoshi
    Department of Biomedical Statistics and Bioinformatics, Graduate School of Medicine, Kyoto University
  • Nakajima, Takako E.
    Department of Early Clinical Development, Graduate school of Medicine, Kyoto University; Kyoto Innovation Center for Next Generation Clinical Trials and iPS Cell Therapy (Ki-CONNECT), Kyoto University Hospital
  • Muto, Manabu
    Department of Therapeutic Oncology, Graduate School of Medicine, Kyoto University; Clinical Bio-Resource Center, Kyoto University Hospital; Kyoto Innovation Center for Next Generation Clinical Trials and iPS Cell Therapy (Ki-CONNECT), Kyoto University Hospital
  • Hamazaki, Yoko
    Department of Life Science Frontiers, Center for iPS Cell Research and Application (CiRA), Kyoto University; Laboratory of Immunobiology, Graduate school of Medicine, Kyoto University
  • 城, 憲秀
  • 日髙, 優
  • 菊池, 理
  • 深堀, 理
  • 澤田, 武志
  • 青木, 雅彦
  • 山本, 正樹
  • 長尾, 美紀
  • 森田, 智視
  • 中島, 貴子
  • 武藤, 学
  • 濵﨑, 洋子
  • 50849552
  • 80884311
  • 10869366
  • 90726837

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  • Author Correction: Impaired CD4+ T cell response in older adults is associated with reduced immunogenicity and reactogenicity of mRNA COVID-19 vaccination

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Whether age-associated defects in T cells impact the immunogenicity and reactogenicity of mRNA vaccines remains unclear. Using a vaccinated cohort (n = 216), we demonstrated that older adults (aged ≥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.

Journal

  • Nature Aging

    Nature Aging 3 (1), 82-92, 2023-01

    Springer Nature

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