Communications medicine · 2026
Antiviral CD4+ T and myeloid cell responses to influenza vaccines are attenuated in older adults.
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Oakes Jared M, Simmons Joshua D, Hager-Nochowicz Cindy, Kirk Leslie, Eason Joan, Halasa Natasha B, Talbot H Keipp, Bailin Samuel S, Castilho Jessica L, Kalams Spyros A
Аннотация
BACKGROUND: Recent influenza vaccine formulations have improved the magnitude of B-cell antibody responses in older adults; however, older adults remain significantly at risk for severe influenza-related illness. Although antibodies are an important metric of vaccine effectiveness, they only represent one aspect of the immune response.
METHODS: In this study, we combined in vitro and ex vivo immune assays with human samples to investigate B cell, CD4+ T cell, and myeloid cell responses to influenza vaccine antigens at the serologic and single-cell level.
RESULTS: We found that older adults mounted antibody titers equivalent to those of younger adults but had fewer influenza-reactive CD4+ T cells and reduced antiviral-associated T helper cell populations. Single-cell transcriptomics revealed that older adults had attenuated interferon transcriptional signatures in T helper and myeloid cell subsets.
CONCLUSIONS: These data suggest that with aging, transcriptional programming alterations in myeloid and T cells contribute to reduced antiviral responses, and formulating vaccines tailored to cellular immune responses is necessary to improve outcomes in older adults.
METHODS: In this study, we combined in vitro and ex vivo immune assays with human samples to investigate B cell, CD4+ T cell, and myeloid cell responses to influenza vaccine antigens at the serologic and single-cell level.
RESULTS: We found that older adults mounted antibody titers equivalent to those of younger adults but had fewer influenza-reactive CD4+ T cells and reduced antiviral-associated T helper cell populations. Single-cell transcriptomics revealed that older adults had attenuated interferon transcriptional signatures in T helper and myeloid cell subsets.
CONCLUSIONS: These data suggest that with aging, transcriptional programming alterations in myeloid and T cells contribute to reduced antiviral responses, and formulating vaccines tailored to cellular immune responses is necessary to improve outcomes in older adults.