The mRNA-based RSV vaccine mRNA-1345 induces robust and durable CD4 ⁺ T cell responses against RSV in younger and older adults
- 1Moderna Inc., Cambridge, MA, USA.
Abstract
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.
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BibTeX
@article{dipiazza2026mrnabased,
title = {{The mRNA-based RSV vaccine mRNA-1345 induces robust and durable CD4 ⁺ T cell responses against RSV in younger and older adults}},
author = {Anthony DiPiazza and Emily Marcisak and Wen-Han Yu and Daniel Makrinos and Hsiao-Hsuan Kuo and Jenna Landy and Shannon McGrath and Xiaolin Chang and Maria Cavallaro and Christopher Wu and Adam Essene and Haining Lin and Laura Walker and Andrea Carfi and Jaap Oostendorp and Robert Paris and Yanbo Sun},
journal = {Science Advances},
year = {2026},
month = oct,
doi = {10.1126/sciadv.aeh4436},
url = {https://www.science.org/doi/10.1126/sciadv.aeh4436},
note = {CC BY},
}
RIS
TY - JOUR
TI - The mRNA-based RSV vaccine mRNA-1345 induces robust and durable CD4 ⁺ T cell responses against RSV in younger and older adults
AU - Anthony DiPiazza
AU - Emily Marcisak
AU - Wen-Han Yu
AU - Daniel Makrinos
AU - Hsiao-Hsuan Kuo
AU - Jenna Landy
AU - Shannon McGrath
AU - Xiaolin Chang
AU - Maria Cavallaro
AU - Christopher Wu
AU - Adam Essene
AU - Haining Lin
AU - Laura Walker
AU - Andrea Carfi
AU - Jaap Oostendorp
AU - Robert Paris
AU - Yanbo Sun
PY - 2026
DA - 2026/10/21
JO - Science Advances
DO - 10.1126/sciadv.aeh4436
UR - https://www.science.org/doi/10.1126/sciadv.aeh4436
AB - 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.
SN - 2375-2548
ER -