Results
asymptomatically infected with SARS-CoV-2), NtAbs
ADVERSE REACTIONS, ADVERSE EVENTS, ADVERSE EVENT, PROLIFERATION, RECRUITMENT, PROLIFERATIVE
Due to the high percentage of individuals immune to SARS-CoV-2 (approximately 16% received at least one dose of the vaccine, and 3.8% officially had COVID-19 in Russia at the moment of enrollment), the pre-screening stage was done to enrich the sample of volunteers with seronegative individuals eligible for enrollment (Trial profile. Due to the high percentage of volunteers with pre-existing COVID-19 immunity in the Russian population by mid-2021, an additional pre-screening stage was implemented no earlier than 3 weeks before vaccination. Screening period included 1 week before vaccination. *Due to competitive recruitment, all sites were screening participants individually; therefore, there was an excess of eligible participants who were not enrolled because the recruitment target was met. 9 participants (one before vaccination, and eight before vaccination with component B) were not included in the safety and immunogenicity analysis; reasons for their withdrawal are listed in Baseline demographic and immunological characteristics of the participants who received two-dose vaccination.Withdrawn participants (n=9) are excluded. The data are n (%) or mean (SD), unless otherwise stated. *Ethnic group was reported by the participants. The safety analysis involved registering solicited local and systemic adverse reactions, including the changes in safety-related laboratory parameters within the first 28 days after the first dose. Adverse events are presented for each of the doses studied (1/10 and 1/5) as well as for each age stratum (12–14 years and 15–17 years old) (Systemic and local solicited adverse events within 28 days after vaccination with 1/10 and 1/5 dose of Sputnik V.Participants who received each dose of vaccine were additionally divided into two age cohorts of 12–14 and 15–17y.o. This table shows the total number (%) of volunteers who developed solicited adverse events, based on the severity: mild [grade 1], moderate [grade 2], and no serious [grade 3] adverse events were reported. Some volunteers had several adverse events of different degrees of severity. Bold values represent summarized results of indicated groups of AEs.The vaccine-induced cellular immune response was evaluated by the proliferative response of CD4+ and CD8+ T cells to antigen-restimulation Parameters of cell-mediated immune response to SARS-CoV-2 glycoprotein in participants before immunisation (day 1) and on day 28 after vaccination with 1/10 or 1/5 dose of Sputnik V. Antigen-specific proliferation of CD4+ Consistent with the lymphoproliferative analysis, vaccination with the 1/5 vaccine dose resulted in a higher (but not statistically significant) increase in the concentration of interferon-γ secretion in peripheral blood mononuclear cells in age-pooled groups (11.81-fold increase) compared to 1/10 vaccine dose (8.05-fold increase) (The antigen-binding antibody response was evaluated by measuring SARS-CoV-2 RBD-specific and S-specific antibodies in volunteers’ sera collected before the immunisation (on day 1) and on days 21, 28, 42, 90, and 180. The analysis was performed immediately after receiving the samples from the day 180 timepoint. Both 1/10 and 1/5 vaccine doses induced statistically significant formation of SARS-CoV-2 RBD-specific (Parameters of humoral immune response in participants vaccinated with 1/10 or 1/5 dose of Sputnik V. Anti-RBD SARS-CoV-2 IgG reciprocal endpoint titres before vaccination (baseline, day 1) and on days 21, 28, 42, 90, and 180 in the participants vaccinated with 1/10 Negative results were obtained for all enrolled volunteers using the anti-S SARS-CoV-2 IgG ELISA test (Mindray Bio-Medical Electronics, China) performed at the local laboratory during the screening. However, the evaluation of the anti-N SARS-CoV-2 antibody response during the study (ELISA kit from Vector-Best, Russia) did reveal individuals with pre-existing anti-N SARS-CoV-2 antibodies before the first vaccination and those who were negative at the day 1 but were tested positive for anti-N IgG (considered as asymptomatically infected with SARS-CoV-2) during the survey. It is worth noting that the differences in RBD-specific antibody responses between different doses observed on day 180 remained statistically significant in a seronegative group (without anti-N IgG antibodies throughout the study) (A higher vaccine dose also resulted in higher seroconversion rates (96% versus 91% on day 180), defined as GMRT>4 in RBD-specific IgGs before and after the vaccination. To evaluate seroconversion rates based on S-specific IgGs expressed in BAU/ml, we applied two different cut-off values (Stratification by age showed that 15-to-17-year-old participants responded with slightly lower titres (mostly statistically insignificant) of RBD-specific IgGs to vaccination with both 1/5 and 1/10 vaccine doses during the whole observation period (from 21 to 180 days) compared to 12-to-14-year-old participants (The analysis of neutralizing antibodies (NtAbs) to SARS-CoV-2 (B.1.1.1) revealed that immunization with both vaccine doses had statistically significant levels already on day 21 (before the boosting vaccination) up to day 180 (Neutralizing antibody response in participants vaccinated with 1/10 or 1/5 dose of Sputnik V. Neutralising antibodies before immunisation (day 1) and on days 21 (before vaccination with component B), 28, 42, 90, and 180, as measured by microneutralisation assay with 100 TCID50, in all participants vaccinated with 1/10 Given the significance of assessing the potential vaccine cross-protection breadth against different lineages of SARS-CoV-2, we examined the virus-neutralizing activity of sera from volunteers vaccinated with 1/10 or 1/5 vaccine dose against two variants of concern (VOC): Delta (B.1.617.2) and Omicron (BA.5) responses were compared with those from the original genetic lineage variant (B.1.1.1) (Finally, we assessed anti-Ad26 and anti-Ad5 NtAbs in volunteers before vaccination and on day 42 with different doses of the Sputnik V vaccine. Upon vaccination with both doses, GMRTs increased statistically significantly on day 42 compared to day 1, but GMRT and seroconversion rates were relatively low. When lower doses (1/10) were used, GMRTs against Ad26 and Ad5 vectors were 25 and 27, resulting in 11% and 22% of seroconversion rates, correspondingly. Upon vaccination with the 1/5 dose eliciting 100% seroconversion rate in NtAbs against SARS-CoV-2, GMRTs were 32 and 49 against Ad26 and Ad5 vectors with seroconversion rates of 13% and 47%, correspondingly (