Abstract
The SARS-CoV-2 mRNA vaccine provides effective protection against viral infection and severe disease by inducing efficient adaptive immunity. However, vaccine efficacy is decreased against emerging variants, and immune memory is relatively short-lived. Here, we added new T cell epitopes to the RBD (receptor-binding domain) mRNA vaccine and identified a SARS-CoV-2 membrane epitope that significantly improved vaccine-induced immunity and protection in vivo. That new vaccine, designated G1-C, induced 8.2-fold higher levels of RBD-specific antibodies than did RBD and enhanced spike-specific T cell and B cell responses. Remarkably, the G1-C modulated hematopoietic stem cell (HSC) differentiation and increased levels of B and NK cells by regulating multiple signaling pathways in bone marrow potentially via Fos, Klf4, and Klf6 transcription factors. Altogether, these findings identify a new vaccine candidate to control viral infection by affecting the lymphoid-myeloid lineage bias and suggest the potential role of T cell epitopes in vaccine design and development.
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Data availability
Single-cell RNA sequencing data are deposited on GEO: GSE281662. The code used for data analysis is available on GitHub: https://github.com/jingw1072/mice-BM-scRNAseq-analysis-code.
Code availability
Single-cell RNA sequencing data are deposited on GEO: GSE281662. The code used for data analysis is available on GitHub: https://github.com/jingw1072/mice-BM-scRNAseq-analysis-code.
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Acknowledgements
We thank Dr. Kristen Jepsen of the Institute of Genomic Medicine at UCSD for help with scRNA-seq, Dr. Neal Sekiya and Ms. Tara Rambled at the Center for AIDS Research at UCSD for flow cytometry analysis, and members of the Rana lab for helpful discussions and advice. This publication includes data generated at the UC San Diego IGM Genomics Center utilizing an Illumina NovaSeq 6000 purchased with funding from a National Institutes of Health SIG grant (#S10 OD026929). This work was supported in part by institutional funds and from grants from the National Institutes of Health (AI125103, CA177322, CA030199, DA046171).
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J.W. designed and performed experiments, analyzed data, and wrote the manuscript draft; J.M. designed and performed experiments, and analyzed data; L.T. and S.B. analyzed the scRNA-seq data; A.S., R.M., J.T., and L.W. performed experiments; D.M.S. provided reagents, S.S. and K.G. participated in experimental design, data analysis and interpretation; T.M.R. conceived and planned the project and participated in experimental design, data analysis, data interpretation, and manuscript writing.
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Wen, J., Moon, J., Tucciarone, L. et al. A new mRNA antigen vaccine induces potent B and T cell responses and in vivo protection against SARS-CoV-2. npj Vaccines (2026). https://doi.org/10.1038/s41541-026-01421-z
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DOI: https://doi.org/10.1038/s41541-026-01421-z
