The mRNA-based RSV vaccine mRNA-1345 induces robust and durable CD4+ T cell responses against RSV in younger and older adults.

Respiratory syncytial virus (RSV) remains a health threat, particularly for infants, older adults, and immunocompromised individuals. Although neutralizing antibodies can help limit infection and viral replication, T cells are essential for reducing disease severity. Assessment of age-related declines in T cell function are important for vaccine evaluation. We used intracellular cytokine staining, activation-induced marker, and Meso Scale Discovery assays and single-cell multiomic profiling to evaluate RSV vaccine mRNA-1345 responses in younger and older adults. mRNA-1345 induced comparable CD4+ and CD8+ T cell responses in both cohorts, with CD4+ responses persisting for 24 months. The CD4+ response was strongly T helper 1 (TH1)-polarized, with increased interferon-γ, interleukin-2, and tumor necrosis factor-α and minimal TH2 cytokines. Both CD4+ and CD8+ T cells showed increased polyfunctionality that remained elevated at 2 years. Single-cell and T cell receptor repertoire analyses showed similar Pre-F-specific phenotypes, transcriptional profiles, and clonal overlap across age groups, supporting robust, durable cellular immunity after mRNA-1345 vaccination. These findings indicate shared vaccine-elicited T cell immunity in adults.