A new mRNA antigen vaccine induces potent B and T cell responses and in vivo protection against SARS-CoV-2

Wen, J.; Moon, J.; Tucciarone, L.; Bu, T.-H.; Sun, A. Y.; Miller, R.; Timis, J.; Wu, L.; Smith, D. M.; Shresta, S.; Gaulton, K. J.; Rana, T. M.

doi:10.64898/2026.03.02.709177

bioRxiv · 10.64898/2026.03.02.709177

A new mRNA antigen vaccine induces potent B and T cell responses and in vivo protection against SARS-CoV-2

Wen, J.·Moon, J.·Tucciarone, L.·Bu, T.-H.·Sun, A. Y.·Miller, R.·Timis, J.·Wu, L.·Smith, D. M.·Shresta, S.·Gaulton, K. J.·Rana, T. M.

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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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Wen, J., Moon, J., Tucciarone, L., Bu, T.-H., Sun, A. Y., Miller, R., Timis, J., Wu, L., Smith, D. M., Shresta, S., Gaulton, K. J., Rana, T. M.. 2026-03-03. A new mRNA antigen vaccine induces potent B and T cell responses and in vivo protection against SARS-CoV-2. https://doi.org/10.64898/2026.03.02.709177

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