DNA-protein COVID-19 combination vaccine containing multiepitope T-cell immunogen and receptor binding domain of the SARS-CoV-2 S protein

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Introduction. During the COVID-19 pandemic, the development of preventive vaccines, including those based on new platforms, became extremely relevant. One such platform is vaccines, which combine, for example, DNA and protein components into a single vaccine. The aim of this study was to investigate the immunogenicity of a DNA vaccine encoding a polyepitopic T-cell immunogen of the SARS-CoV-2 virus, combined with the recombinant RBD protein (the receptor-binding domain of the SARS-CoV-2 virus S protein, Wuhan-Hu-1 strain) conjugated to a polycationic carrier – polyglucin-spermidine (PGS), and to assess the contribution of individual components to the development of an immune response in BALB/c mice. Materials and methods. To create the DNA vaccine (pBSI-COV-Ub), we used a strategy of designing an artificial polyepitope immunogen consisting of conserved immunodominant fragments of various structural proteins of the SARS-CoV-2 virus, containing a large number of T-lymphocyte epitopes: helper and cytotoxic. The recombinant RBD protein was conjugated with the polycation PGS, and upon mixing it with DNA, it formed the vaccine complex CCV–BSI, whose immunogenic properties were investigated in this work. Results. Immunization of BALB/c mice with the CCV–BSI combined construct resulted in the induction of high antibody titers with neutralizing activity against live SARS-CoV-2 virus, as well as the formation of a virus-specific T-cell response, as demonstrated by ELISA, neutralization assay and ELISpot. It has been shown that the protein component contributes to the humoral immune response, while DNA contributes to the cellular immune response. Administration of the recombinant RBD protein led to the induction of only antibodies, administration of the DNA vaccine led to the induction of only a T-cell response, and administration of the combined preparation led to the induction of both a humoral immune response and specific T cells. Conclusion. The unique combination of DNA and protein within a single vaccine construct allows for overcoming the limitations of each of these vaccine types and leads to the induction of both arms of immunity. The protein component can be replaced according to the current viral strain, and a universal T-cell immunogen can provide a response to a wide range of circulating variants. This platform can be further used to develop vaccines against various highly variable viruses.

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