Through 4 June 2021, COVID-19 has caused over 172.84 million cases of infection and 3.71 million deaths worldwide. Due to its rapid dissemination and high mutation rate, it is essential to develop a vaccine harboring multiple epitopes and efficacious against multiple variants to prevent the immune escape of SARS-CoV-2. An in silico approach based on the viral genome was applied to identify 19 high-immunogenic B-cell epitopes and 499 human leukocyte antigen (HLA)-restricted T-cell epitopes. Thirty multi-epitope peptide vaccines were designed by iNeo-Suite and manufactured by solid-phase synthesis. Docking analysis confirmed stable hydrogen bonds of epitopes with their corresponding HLA alleles. When four peptide candidates derived from the spike protein of SARS-CoV-2 were selected to immunize mice, a significantly larger amount of total IgG in serum, as well as an increase of CD19+ cells in the inguinal lymph nodes, were observed in the peptide-immunized mice compared to the control. The ratios of IFN-γ-secreting lymphocytes in CD4+ or CD8+ T-cells in the peptide-immunized mice were higher than those in the control mice. There were also a larger number of IFN-γ-secreting T-cells in the spleens of peptide-immunized mice. The peptide vaccines in this study successfully elicited antigen-specific humoral and cellular immune responses in mice. To further validate the safety and efficacy of this vaccine, animal studies using a primate model, as well as clinical trials in humans, are required.
【저자키워드】 COVID-19, SARS-CoV-2, Vaccine, peptide, immunoinformatics, epitope, 【초록키워드】 IgG, Efficacy, clinical trial, Cellular immune response, variant, Infection, Antigen, lymphocyte, serum, Immune escape, mice, humans, death, B-cell epitope, T-cell, dissemination, docking analysis, peptide vaccine, T-cell epitopes, lymph nodes, spleen, Hydrogen bond, viral genome, humoral, leukocyte, in silico Approach, HLA alleles, candidate, CD4+, high mutation rate, CD19+, Prevent, Cell, selected, identify, develop, caused, significantly, required, applied, the spike protein, immunize, elicited, CD8+ T-cell, multi-epitope peptide vaccine, multiple epitope,