Preclinical valuation of immunogenicity and effectiveness of inactivated cultural vaccine experimental patterns against coronaviral infection COVID-19

Relevance. Research on the development of new, more advanced vaccines against Covid-19, both based on modern technologies and traditional inactivated ones, remains relevant. In the "48 Central Research Institute" of the Ministry of Defense of the Russian Federation, together with the Yaroslavl Factory of ready-made Dosage Forms of JSC R-Pharm, a cultural (based on Vero (B) cell culture) inactivated with beta-propiolactone chromatographically purified vaccine against coronavirus infection Covid-19 was developed. The aim of the work is to evaluate the results of preclinical studies on its immunogenicity and protective effectiveness in animal experiments. Materials and methods. The immunogenicity and protective activity of experimental vaccine samples with adjuvants aluminum hydroxide and CpG 1018 were evaluated, including in comparison with Sputnik V, after double immunization of Syrian hamsters with an interval of 21 days with intranasal infection with the virulent SARS-CoV-2 virus at a dose of 105 Plaqueforming units/individual. In an experiment on monkeys, the effects of the vaccine on double immunization were evaluated: humoral (virus neutralizing antibodies titer) and cellular immunity indicators for 1 year. Results and discussion. The optimal dose of the vaccine was selected – 15 mcg of protein and the composition of the adjuvants included in it was determined: 500 mcg of aluminum hydroxide and 10 mcg of synthetic oligodeoxynucleotide CpG 1018. The inactivated sorbed vaccine against Covid-19 coronavirus infection, when administered twice with an interval of 21 days, induces the formation of viral neutralizing antibodies in 80-100% of Syrian hamsters at titers of 1:20 or more 21 days after the completion of the immunization cycle and is characterized by a lung protection index ≥ 3.2 lg on the 6th day after infection with 105Plaque-forming units of virulent virus (variant “Delta”). The inactivated sorbed vaccine is capable of generating a humoral immune response in rhesus monkeys to both the “Delta” variant and the “Omicron” variant of the SARS-CoV-2 virus. Virus neutralizing antibodies for both variants persists in 100% of vaccinated animals for 180 days after double immunization. By 42 days after the completion of vaccination, there is an increase in cytotoxic T lymphocytes and a decrease in total B lymphocytes. Conclusions. The inactivated sorbed purified vaccine against Covid-19 coronavirus infection, when administered twice, is immunogenic for Syrian hamsters and protects them from intranasal infection with 1•105 Plaqueforming units of virulent virus. The vaccine is capable of generating a specific humoral immune response to both the “Delta” variant and the “Omicron” variant of the SARS-CoV-2 virus. Virus neutralizing antibodies for both variants persists in 100 % of animals for 180 days after double immunization. The effect of immunization on cellular immunity is shown.