Abstract
Despite evidence of varying vaccine effectiveness, T cell responses to rotavirus (RV) vaccines remain incompletely studied. To address this research gap, RV-specific T cells in the blood of infants pre- and post-monovalent RV vaccination (RV1) were analyzed for memory recall and functionality using RV-specific peptide pool stimulation. We find that RV vaccine elicits heterogenous responses with respect to cellular and humoral immunity. T cell responses to RV vaccine are detectable in the periphery, though poorly functional. Vaccination induces Th2-biased conventional effector memory and central memory CD4 + T cells, as suggested by chemokine receptor profiles, though the response wanes by 8 months post vaccination. The presence of preexisting immunity results in no significant increase in either RV-specific IgA or T cells after vaccination. Our data provides the first in-depth assessment of RV-specific T cell responses induced by vaccine, demonstrating patterns of negative and positive association with response that may play a role in protection against rotavirus disease.
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Data availability
Source data for all figures, including those in the supplement, are provided with this paper. Full data for rotavirus and CMV responses are available at the Open Science Framework as is the code and data used to generate fold change volcano plots https://doi.org/10.17605/OSF.IO/D8SJ2. FCS files used in the analyses have been deposited in the following Zenodo databases, https://doi.org/10.5281/zenodo.17363217, https://doi.org/10.5281/zenodo.17364328, https://doi.org/10.5281/zenodo.17364765.
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Acknowledgements
This work was funded by a National Institute of Health/National Institute of Child Health and Human Development (NIH/NICHD) R01 grant: R01 HD100542. Flow cytometry experiments were carried out at the core facility at the La Jolla Institute for Immunology.
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Conceptualization: P.S.P. Methodology: A.R.N., Y.L., Z.CW., T.J.O., A.S., R.d.S.A., P.S.P. Formal analysis: A.R.N., Y.L., M.K., P.S.P. Investigation: A.R.N., Y.L., Z.CW., M.K., W.A.C., J.J., J.N., R.A.N.H., Y.R.A., D.D., Z.W.T., R.G.D.L., T.J.O., P.S.P. Resources: R.d.S.A., A.S. Data curation: A.R.N., W.A.C., P.S.P. Writing—original draft and visualization: A.R.N., P.S.P. Writing—review and editing: A.R.N., Z.CW., Y.L., M.K., Z.W.T., R.G.D.L., T.J.O., R.d.S.A., A.S., P.S.P. Supervision and funding acquisition: P.S.P.
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Nicols, A.R., Lee, Y., Congrave-Wilson, Z. et al. Peripheral rotavirus-specific T-cell responses following monovalent oral rotavirus vaccine in infants. npj Vaccines (2026). https://doi.org/10.1038/s41541-026-01405-z
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DOI: https://doi.org/10.1038/s41541-026-01405-z


