The urgent need for effective and safe agents for the treatment and prevention of viral infections has been put into spotlight in connection with the pandemic of the new coronavirus infection COVID-19. The world scientific community has begun accelerated development of vaccines that can activate both cellular and humoral immunity and form a long-term immunological memory. However, data on the virulence of proteins encoded by the viral genome are still insufficient. In this regard, it is important to search for the most immunogenic epitopes not only in the composition of the spike protein and other membrane proteins of the SARS-CoV-2 virus, but also the proteins of the viral capsid and nucleoprotein. Recently, immuno-informational analysis of the full-sized genome of the virus has been published and a ranked list of immunogenic epitopes has been compiled. The list contains top nonameric epitopes of helper and cytotoxic T cells, common to all MHC alleles, encompassing all prevailing HLA supertypes in the population. It turned out that membrane proteins and spike protein may be less immunogenic compared to other proteins of the virus, including non-structural ones. All 57 identified SARS-CoV-2 epitopes in the human proteome are not represented.
The goal of this project is to develop a prototype vaccine construct for the treatment and prevention of COVID-19, containing a set of the most immunogenic T-cell epitopes. Liposomes will be used as adjuvant carrier systems, since they are multifunctional, provide the ability to create a wide variety of designs, and are the most biocompatible. Some 20-25 candidate nonameric peptides selected from the ranked list of epitopes will be synthesized, and methods for incorporating several sets of 5-10 peptides into liposomes will be developed. An immunostimulant CpG oligonucleotide in the form of a lipid conjugate, the synthesis of which will be carried out during the implementation of the project, will also be included in liposomes. The resulting constructs will be used to vaccinate experimental animals (mice) and evaluate T-cell immunity, study humoral immunity using the multiplex immunological system developed within the project to assess the contribution of each of the peptides, and also to study the toxicological characteristics of the selected vaccine formulations.
Detection of immunogenic epitopes that are not related to the spike protein and membrane proteins of the SARS-CoV-2 virus should open the prospect of developing vaccines, the effectiveness of which will depend little on mutations in the viral genome. It is expected that the resulting formulations can serve as a prototype for creating safe and effective vaccines for the treatment and prevention of COVID-19.