Introduction. Many different vaccines for the prevention of COVID-19 have received emergency use approval in the shortest possible time. Due to the high rate of variability of the pathogen, in this study we analyzed the variability of the structural proteins of the SARS-CoV-2 virus and compared their protective potential in protecting animals from COVID-19. The aim of the study was to compare the protective potential of the SARS-CoV-2 structural proteins in protecting animals from COVID-19. Materials and methods. The SARS-CoV-2 virus was used in the study. Transgenic mice B6.Cg-Tg(K18-ACE2)2Prlmn/J (F1) were used as model animals. Recombinant adenoviral vectors rAd5-S, rAd5-N, rAd5-M were used for immunization of animals. Various genetic, virological and immunological methods, as well as methods of working with animals, were used in the study. Results. The largest number of amino acid substitutions in the structural proteins of different SARS-CoV-2 variants was detected in glycoprotein S, the smallest — in nucleoprotein N. In the COVID-19 animal model, it was shown that only the use of glycoprotein S as a vaccine antigen allows to form protective immunity that protects 100% of animals from a lethal infection caused by the SARS-CoV-2 virus, while the use of protein N protects 50% of animals from a lethal infection, and protein M does not have a protective potential. Conclusion. The data obtained, as well as the analysis of the epidemiological efficacy of various mRNA and vector vaccines, demonstrate that the use of the SARS-CoV-2 glycoprotein S as an antigen allows to form the highest level of protection. Due to the constant change in circulating variants of the SARS-CoV-2 virus, the decrease in the effectiveness of the vaccines with the original antigen composition against new variants of the virus and the continuing high incidence of COVID-19, it is necessary to continuously monitor the effectiveness of vaccines against new variants of the virus and promptly update the antigen composition of vaccines when a decrease in effectiveness is detected.
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