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Title: Relative deficiency in interferon-γ-secreting CD4+T cells is strongly associated with poorer COVID-19 vaccination responses in older adults
Authors: Ho, Vanda WT 
Boon, Low Heng 
Cui, Jianzhou 
Juequn, Zhou 
Shunmuganathan, Bhuvaneshwari 
Gupta, Rashi 
Tan, Nikki YJ 
Qian, Xinlei 
Purushotorman, Kiren 
Fong, Siew-Wai 
Renia, Laurent 
Ng, Lisa FP 
Angeli, Veronique 
Chen, Jinmiao 
Kennedy, Brian K 
Ong, Catherine WM 
Macary, Paul A 
Keywords: Science & Technology
Life Sciences & Biomedicine
Cell Biology
Geriatrics & Gerontology
antigen-specific T-cell response
COVID-19 mRNA vaccine
older adults
Issue Date: 1-Jan-2024
Publisher: WILEY
Citation: Ho, Vanda WT, Boon, Low Heng, Cui, Jianzhou, Juequn, Zhou, Shunmuganathan, Bhuvaneshwari, Gupta, Rashi, Tan, Nikki YJ, Qian, Xinlei, Purushotorman, Kiren, Fong, Siew-Wai, Renia, Laurent, Ng, Lisa FP, Angeli, Veronique, Chen, Jinmiao, Kennedy, Brian K, Ong, Catherine WM, Macary, Paul A (2024-01-01). Relative deficiency in interferon-γ-secreting CD4+T cells is strongly associated with poorer COVID-19 vaccination responses in older adults. AGING CELL. ScholarBank@NUS Repository.
Abstract: Although the two-dose mRNA vaccination regime provides protection against SARS-CoV-2, older adults have been shown to exhibit poorer vaccination responses. In addition, the role of vaccine-induced T-cell responses is not well characterised. We aim to assess the impact of age on immune responses after two doses of the BNT162b2 mRNA vaccine, focussing on antigen-specific T-cells. A prospective 3-month study was conducted on 15 young (median age 31 years, interquartile range (IQR) 25–35 years) and 14 older adults (median age 72 years, IQR 70–73 years). We assessed functional, neutralising antibody responses against SARS-CoV-2 variants using ACE-2 inhibition assays, and changes in B and T-cell subsets by high-dimensional flow cytometry. Antigen-specific T-cell responses were also quantified by intracellular cytokine staining and flow cytometry. Older adults had attenuated T-helper (Th) response to vaccination, which was associated with weaker antibody responses and decreased SARS-CoV-2 neutralisation. Antigen-specific interferon-γ (IFNγ)-secreting CD4+ T-cells to wild-type and Omicron antigens increased in young adults, which was strongly positively correlated with their neutralising antibody responses. Conversely, this relationship was negative in older adults. Hence, older adults' relative IFNγ-secreting CD4+ T cell deficiency might explain their poorer COVID-19 vaccination responses. Further exploration into the aetiology is needed and would be integral in developing novel vaccination strategies and improving infection outcomes in older adults.
Source Title: AGING CELL
ISSN: 1474-9718
DOI: 10.1111/acel.14099
Appears in Collections:Staff Publications

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