The unprecedented in recent history global COVID-19 pandemic urged the implementation of all existing vaccine platforms to ensure the availability of the vaccines against COVID-19 to every country in the world. Despite the multitude of high-quality papers describing clinical trials of different vaccine products, basic detailed data on general toxicity, reproductive toxicity, immunogenicity, protective efficacy and durability of immune response in animal models are scarce. Here, we developed a β-propiolactone-inactivated whole virion vaccine CoviVac and assessed its safety, protective efficacy, immunogenicity and stability of the immune response in rodents and non-human primates. The vaccine showed no signs of acute/chronic, reproductive, embryo- and fetotoxicity, or teratogenic effects, as well as no allergenic properties in studied animal species. The vaccine induced stable and robust humoral immune response both in form of specific anti-SARS-CoV-2 IgG and NAbs in mice, Syrian hamsters, and common marmosets. The NAb levels did not decrease significantly over the course of one year. The course of two immunizations protected Syrian hamsters from severe pneumonia upon intranasal challenge with the live virus. Robustness of the vaccine manufacturing process was demonstrated as well. These data encouraged further evaluation of CoviVac in clinical trials.
Global polio eradication requires both safe and effective vaccines, and safe production processes. Sabin oral poliomyelitis vaccine (OPV) strains can evolve to virulent viruses and result in poliomyelitis outbreaks, and conventional inactivated poliomyelitis vaccine (Salk-IPV) production includes accumulation of large stocks of neurovirulent wild polioviruses. Therefore, IPV based on attenuated OPV strains seems a viable option. To increase the global supply of affordable inactivated vaccine in the still not-polio free world we developed an IPV made from the Sabin strains–PoliovacSin. Clinical trials included participants 18–60 years of age. A phase I single-center, randomized, double-blind placebo-controlled clinical trial included 60 participants, who received one dose of PoliovacSin or Placebo. A phase II multicenter, randomized, double-blind, comparative clinical trial included 200 participants, who received one dose of PoliovacSin or Imovax Polio. All vaccinations were well tolerated, and PoliovacSin had a comparable safety profile to the Placebo or the reference Imovax Polio preparations. A significant increase in neutralizing antibody levels to polioviruses types 1–3 (Sabin and wild) was observed in PoliovacSin and Imovax Polio vaccinated groups. Therefore, clinical trials confirmed good tolerability, low reactogenicity, and high safety profile of the PoliovacSin and its pronounced immunogenic properties. The preparation was approved for clinical trials involving infants.
We present the results of a randomized, double-blind, placebo-controlled, multi-center clinical trial of the tolerability, safety, and immunogenicity of the inactivated whole virion concentrated purified coronavirus vaccine CoviVac in adult volunteers aged 18-60.
Safety of the vaccine was assessed in 398 volunteers who received two doses of the vaccine (n=298) or placebo (n=100). The studied vaccine has shown good tolerability and safety. No deaths, serious adverse events (AE), or other significant AE related to vaccination have been detected. The most common AE in vaccinated participants was pain at the injection site (p<0.05).
Immunogenicity assessment was performed in 167 volunteers (122 vaccinated and 45 in Placebo Group) separately for the participants who were anti-SARS-CoV-2 nAB negative (69/122 in Vaccine Group and 28/45 in Placebo Group) or positive (53/122 in Vaccine Group and 17/45 in Placebo Group) at screening.
At Day 42 after the first immunization the seroconversion rate in participants who were seronegative at screening was 86.9% with average the geometric mean neutralizing antibody (nAB) titer of 1:20. Statistically significant (p<0.05) increase of IFN-γ production by peptide-stimulated T-cells was observed at Days 14 and 21 after the first immunization.
In participants who were seropositive at screening but had nAB titers below 1:256 the rate of 4-fold increase in nAB levels was 85.2%, while in the participants with nAB titers >1:256 the rate of 4-fold increase in nAB levels was below 45%. For the participants who were seropositive at screening the second immunization did not lead to a significant increase in nAB titers.
In conclusion, inactivated vaccine CoviVac has shown good tolerability and safety, with 86.9% seroconversion rates in participants, who were seronegative at screening. In participants who were seropositive at screening and had nAB titers below 1:256, a single immunization lead to a 4-fold increase in nAB levels in 85.2% cases.
Aim. A controlled study was carried out regarding horizontal transmission of the vaccine strain of parotitic virus (PV). Materials and methods. 20 couples took part in the study. Monitoring of both spouses was carried out for 42 days after a single vaccination of one of them, levels of specific IgM and IgG in sera and virus-neutralizing IgG in sera and saliva were studied in dynamics, PV RNA was also determined in sera and saliva samples. Amplified fragments of F, SH, NP and HN genes of PV were sequenced. Results. Transfer of PV vaccine strain was registered in all the couples except for one. Except a single contact spouse, all the rest demonstrated formation of a specific immune response. At month 4 of the observation, group of vaccinated spouses differed significantly from a group of contact spouses only by total content of specific IgG and their avidity. Conclusion. Horizontal transmission of PV strain was demonstrated in couples after vaccination of one of the spouses and resulted in formation of specific immunity in 95% of contact individuals.
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