Development of the Inactivated QazCovid-in Vaccine: Protective Efficacy of the Vaccine in Syrian Hamsters

Abstract

In March 2020, the first cases of the human coronavirus disease COVID-19 were registered in Kazakhstan. We isolated the SARS-CoV-2 virus from clinical materials from some of these patients. Subsequently, a whole virion inactivated candidate vaccine, QazCovid-in, was developed based on this virus. To develop the vaccine, a virus grown in Vero cell culture was used, which was inactivated with formaldehyde, purified, concentrated, sterilized by filtration, and then adsorbed on aluminum hydroxide gel particles. The formula virus and adjuvant in buffer saline solution were used as the vaccine. The safety and protective effectiveness of the developed vaccine were studied in Syrian hamsters. The results of the studies showed the absolute safety of the candidate vaccine in the Syrian hamsters. When studying the protective effectiveness, the developed vaccine with an immunizing dose of 5 μg/dose specific antigen protected animals from a wild homologous virus at a dose of 104.5 TCID50/mL. The candidate vaccine induced the formation of virus-neutralizing antibodies in vaccinated hamsters at titers of 3.3 ± 1.45 log2 to 7.25 ± 0.78 log2, and these antibodies were retained for 6 months (observation period) for the indicated titers. No viral replication was detected in vaccinated hamsters, protected against the development of acute pneumonia, and ensured 100% survival of the animals. Further, no replicative virus was isolated from the lungs of vaccinated animals. However, a virulent virus was isolated from the lungs of unvaccinated animals at relatively high titers, reaching 4.5 ± 0.7 log TCID50/mL. After challenge infection, 100% of unvaccinated hamsters showed clinical symptoms (stress state, passivity, tousled coat, decreased body temperature, and body weight, and the development of acute pneumonia), with 25 ± 5% dying. These findings pave the way for testing the candidate vaccine in clinical human trials.

Efficacy and safety of an inactivated whole-virion vaccine against COVID-19, QazCovid-in®, in healthy adults: A multicentre, randomised, single-blind, placebo-controlled phase 3 clinical trial with a 6-month follow-up

“…In Kazakhstan, the technology for production of formaldehyde-inactivated, adjuvanted with aluminium hydroxide, whole-virion vaccine QazCovid-in® against COVID-19 has been developed, and preclinical studies 27 as well as phases 1/2 clinical trials of the vaccine are now completed. 28 The QazCovid-in® vaccine is proven to be safe, well-tolerated, and immunogenic in two age groups, 18–49 and ≥50 years.…”

An overview on inactivated and live‐attenuated SARS‐CoV‐2 vaccines

“…It is a two‐dose, intramuscular, and formalin‐inactivated vaccine adjuvanted with aluminum hydroxide. 56 Phase 1/2 clinical trial (NCT04530357) was conducted in two parts to evaluate the safety, tolerability, and immunogenicity of vaccine based on the comparison of antibody titers in serum samples before and after vaccination, which was measured by microneutralization test (MNA) and enzyme linked immunosorbent assay (ELISA) tests. QazVac vaccine testing on 44 subjects aged 18–50 years demonstrated its favorable tolerability in phase 1 part of phase 1/2 clinical trial, and MNA showed seroconversion in 100% of subjects after two doses of the vaccine.…”

“…QazCovid‐in, commercially known as QazVac vaccine, was developed by the Research Institute for Biological Safety Problems in Kazakhstan. It is a two‐dose, intramuscular, and formalin‐inactivated vaccine adjuvanted with aluminum hydroxide 56 . Phase 1/2 clinical trial (NCT04530357) was conducted in two parts to evaluate the safety, tolerability, and immunogenicity of vaccine based on the comparison of antibody titers in serum samples before and after vaccination, which was measured by microneutralization test (MNA) and enzyme linked immunosorbent assay (ELISA) tests.…”

Near-Complete Genome Sequence of a SARS-CoV-2 Variant B.1.1.7 Virus Strain Isolated in Kazakhstan

“…The first human cases of coronavirus infection COVID-19 (coronavirus disease 2019) were recorded in the Republic of Kazakhstan (RK) in mid-March 2020 ( 6 ). According to World Health Organization data, on 14 June 2022, a total of 1,395,068 confirmed cases were registered in the Republic of Kazakhstan, resulting in 19,017 deaths ( 7 ).…”