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

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.