Activating the leukocytes by short synthetic peptides in vitro as a stage in the creation of treatment-prophylactic vaccines against COVID-19

Abstract

Experience with pandemics strongly suggests that vaccination of the population in all categories should be a national priority. The choice of a vaccine production platform should be made in such a way as to achieve an optimal effect at the lowest possible cost. A peptide vaccine or a protein platform vaccine could serve these purposes. Oral and intranasal vaccines are also attractive due to the ease of administration to different population groups, and the resulting immunity is not inferior to that of intramuscularly administered vaccines.In this work, synthetic peptides representing the fragments of the surface protein SARS-CoV-2 were investigated. The peptides were prepared by classical peptide synthesis, with peptide No. 1 (Lys-Ile-Ala-Asp-Tyr-Asn-Tyr-Lys-Leu) being immunodominant for the HLA-A02:01 phenotype with a low calculated concentration of half-maximum inhibition. Peptide No. 2 (Val-Arg-Gln-Ala-Pro-Asn-Gly-Gln-Thr) was chosen as control and is not immunodominant for the HLA-A02:01 phenotype, with a high estimated concentration of half-maximum inhibition (IC50).80 persons were questionnaired and 78 volunteers were examined. Cellular immunity parameters were analyzed using a Cytomics FC 500 flow cytometer and gamma interferon (IFN-γ) was determined by ELISA. The results were processed using Statistica 10 software. As a result, a new method was tested to evaluate the activation of blood leukocytes by synthetic peptides. Regardless of the HLA-A phenotype of the study subjects, the peptides were able to bind to leukocytes, indicating a universal response to foreign peptides, especially to innate immune cells. Peptide No. 2 with high calculated IC50, compared to peptide No. 1 with low calculated IC50, showed significantly higher binding to lymphocytes and monocytes and activation of basophils. The peptides used in this work showed that they interact with leukocytes, activating them through the secretion of IFN-γ. Thus, our work demonstrates an approach to creating a peptide vaccine in the in vitro research phase, as well as to studying the antiviral response by the IFN-γ growth in response to the peptides.