A bivalent COVID-19 mRNA vaccine combined B-cell and T-cell immunogens elicits strong humoral and cellular immune response in mice

Both humoral and cellular immune responses are known to be crucial in the fight against SARS-CoV-2.

The aim of this work was to evaluate the immunogenicity profile of a bivalent mRNA vaccine encoding a multi-epitope T-cell immunogen and a B-cell immunogen as a receptor-binding domain of the S protein of the SARS-CoV-2 virus in BALB/c mice.

Two mRNA vaccines were obtained: mRNA-BSI encoding fragments of the S, M, N, and E proteins of the SARS-CoV-2 virus enriched with the large number of T-cell epitopes and mRNA-RBD encoding the receptor-binding domain (RBD) of the SARS-CoV-2 S protein. BALB/c mice were immunized with 10 μg of individual mRNA preparations or a 10 μg + 10 μg mixture intramuscularly in LNP vehicles twice with a three-week interval.

RBD-specific ELISA and neutralization assay (Wuhan and Omicron (BA.5.2) strains) showed an 2–4-fold increase in antibody titers in sera of mice immunized with the mixture of mRNA constructs compared to the group of mice that received only mRNA-RBD (mRNA-BSI did not induce a humoral response).

A T-cell response assay showed that mice that received the bivalent mRNA vaccine had a higher level of IFN-γ T-cell activation compared to the group that recieved the individual mRNA vaccine. In addition, the increases of IL-2 and TNF-α were not particularly significant, and the absence of IL-4 was noted.

The results indicate the formation of a pronounced humoral and T-cell response and a Th1 shift in mice that received the bivalent mRNA vaccine, encoding B-cell and T-cell immunogens.

The study was carried out as part of the state assignment of the FBIS SRC Virology and Biotechnology "Vector" of Rospotrebnadzor.