Sustained antigen-specific CD8+ T cell immunity post–mRNA booster requires notch pathway activation
Abstract
Abstract Messenger RNA (mRNA) vaccines effectively induce protective immunity, but antigen-specific CD8+ T cell responses exhibit limited persistence. In this study, we aimed to assess CD8+ T cell responses following a third dose of the Pfizer BNT162b2 COVID-19 vaccine and identify factors contributing to their longevity. Using HLA tetramers, we analyzed antigen-specific CD8+ T cells in 141 vaccinated individuals (86.5% female) and identified 2 groups: those with strong responses (strong group) and those with weak responses (weak group) 6 mo after the third mRNA vaccination. Transcriptomic analysis revealed that Notch signaling was upregulated in the strong group, and in vitro, the inhibition of Notch signaling significantly reduced CD8+ T cell expansion. These findings suggest that Notch signaling may contribute to maintain long-term antigen-specific CD8+ T cell responses following mRNA vaccination. Targeting this pathway could offer novel strategies for enhancing vaccine-induced cellular immunity and long-lasting protection.
Article Details
Journal Info
The Journal of Immunology
American Association of Immunologists
Authors (18)
Takuto Nogimori
National Institutes of Biomedical Innovation, Health and Nutrition
Yoshinori Okina
Laboratory of Precision Immunology, Center for Intractable Diseases and ImmunoGenomics, National Institutes of Biomedical Innovation, Health, and Nutrition , Osaka,
Yuji Masuta
National Institutes of Biomedical Innovation, Health and Nutrition
Mayu Kumamoto
National Institutes of Biomedical Innovation, Health and Nutrition
Tomoka Matsuura
Department of Public Health, Graduate School of Medicine, Osaka Metropolitan University , Osaka,
Natsuko Kaku
Research Center for Infectious Disease Sciences, Graduate School of Medicine, Osaka Metropolitan University , Osaka,
Satoko Ohfuji
Department of Public Health, Graduate School of Medicine, Osaka Metropolitan University , Osaka,
Tetsuo Kase
Department of Public Health, Graduate School of Medicine, Osaka Metropolitan University , Osaka,
Kyoko Kondo
OMU Core Facilities Life Sciences Section, Osaka Metropolitan University , Osaka,
Yu Nakagama
Osaka Metropolitan University, Osaka , Japan
Sachie Nakagama
Osaka Metropolitan University, Osaka , Japan
Yuko Nitahara
Research Center for Infectious Disease Sciences, Graduate School of Medicine, Osaka Metropolitan University , Osaka,
Shokichi Takahama
Laboratory of Precision Immunology, Center for Intractable Diseases and ImmunoGenomics, National Institutes of Biomedical Innovation, Health, and Nutrition , Osaka,
Hiroshi Kakeya
Victor Appay
Univ. Bordeaux
Wakaba Fukushima
Department of Public Health, Graduate School of Medicine, Osaka Metropolitan University , Osaka,
Yasutoshi Kido
Osaka Metropolitan University, Osaka , Japan
Takuya Yamamoto