Antiviral CD4⁺ T and myeloid cell responses to influenza vaccines are attenuated in older adults.

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: T cell, and myeloid cell responses to influenza vaccine antigens at the serologic and single-cell level. RESULTS: 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.