Evaluation of Immunogenicity of Inactivated Whole-Virion Booster Vaccine against SARS-CoV-2 in a phase I, II Clinical Trial
Authors: Stoma I. O. , Voropaev E. V. , Mikhailova E. I. , Korsak K. S. , Osipkina O. V. , Molchanova A. V. , Kovalev A. A. , Los D. M. , Ziatskov A. A. , Shaforost A. S. , Yatsuk M. N. , Braga A. Yu. , Trofimova N. V. , Dronina A. M. , Gasich E. L. , Gorbunov V. A. , Hancharou A. Ev. 
Published: January 2025

Relevance. The development and production of own vaccine contributes to the growth of professional competencies of the scientific community, improvement and modernization of the country's industrial production.Aims. To evaluate the immunogenicity parameters of whole-virion vaccine against SARS-CoV-2 in a phase I, II clinical trial (up to day 180).Materials & Methods. The clinical study included a phase I/II trial. In Phase I, a sequential allocation of subjects (1:1) by open-label method into two groups with a single administration of vaccine at dose 1 and at dose 2 was performed. In phase II (double-blind randomized), subjects were allocated to immunization with vaccine at doses 1, 2 or placebo in a 1:1:1 ratio. To evaluate the immunogenicity of an inactivated whole-virion booster vaccine against SARS-CoV-2 («BelCovidVac») in 135 healthy subjects (18–50 years of age in phase 1 and 18-60 years of age in phase 2) previously vaccinated/recovered from COVID-19. IgG concentration (BAU/mL) to the S-protein of SARS-CoV-2 was measured by the «SARS-CoV-2-IgG quantitative-ELISA-BEST» ELISA kit, viral neutralising activity of sera and proliferative activity of T-lymphocytes were evaluated, geometric mean (GMC) of IgG concentration was calculated, geometric mean of virus neutralizing activity titer (GMT compared to baseline. Statistical processing of the data was performed using the R programming language.Results. The values of fold change in IgG concentration to SARS-CoV-2 on day 42 and 90 in subjects who received «BelCovidVac» vaccine were significantly higher than those of subjects who received placebo (p=0,05, p=0,02, respectively). The value of the fold change in the titer of viral neutralizing activity in the study subjects who received «BelCovidVac» vaccine was significantly higher than the values of the subjects who received placebo (p=0,02). A statistically significant positive correlation (ρSp=0,51 p=0,0005) between the content of antigen-specific T-cells and the level of IgG after 28 days in the studied subjects and between the fold change in the titer of viral neutralizing activity of sera and the fold change in IgG concentration (ρSp = 0,40 p<0,001) was established. On day 180, all groups of subjects show a decrease in antigen-specific IgG concentrations to the initial level.Discussion. At the time of the search for volunteers and the beginning of the clinical trial of the vaccine «BelKovidVac» the immune layer of the population had already been formed, which made the task of the researchers more difficult. But the vaccine «BelKovidVac» showed its immunogenicity, as evidenced by the results of the study.Conclusions. A significant increase in GMC IgG and GMT viral neutralizing activity of sera in the group vaccinated with «BelCovidVac» and no significant increase in GMC IgG and GMT viral neutralizing activity of sera in the placebo group were revealed, which is the evidence of immune response stimulation as a result of «BelCovidVac» vaccine administration and its efficacy.