T-Cell Epitope-Based SARS-CoV-2 DNA Vaccine Encoding an Antigen Fused with Type 1 Herpes Simplex Virus Glycoprotein D (gD)

Authorized SARS-CoV-2 vaccines elicit both antibody and T-cell responses; however, benchmark correlates and update decisions have largely emphasized neutralizing antibodies. Motivated by the complementary role of cellular immunity, we designed a prototype polyepitope DNA vaccine encoding conserved human and mouse T-cell epitopes from non-structural proteins of the original strain SARS-CoV-2 lineage. Epitope selection was guided by in silico predictions for common HLA class I alleles in the Brazilian population and the mouse H-2Kb haplotype. To enhance immunogenicity, the polyepitope sequences were fused to glycoprotein D (gD) from Herpes Simplex Virus 1 (HSV-1), an immune activator of dendritic cells (DCs), leading to enhanced activation of antigen-specific T-cell responses. Mice were immunized with two doses of the electroporated DNA vaccine encoding the gD-fused polyepitope, which induced robust interferon-gamma- and tumor necrosis factor-alpha-producing T cell responses compared to control mice. In addition, K18-hACE2 transgenic mice showed protection against intranasal challenge with the original SARS-CoV-2 strain, with reduced clinical symptoms, less weight loss, and decreased viral burden in both lung and brain tissues. The results experimentally confirm the protective role of T cells in vaccine-induced protection against SARS-CoV-2 and open perspectives for the development of universal anti-coronavirus vaccines.