A new inactivated whole-virion QazCovid-in® vaccine against COVID-19 was developed from SARS-CoV-2 isolated in Kazakhstan, inactivated by formaldehyde, and adjuvanted with aluminium hydroxide. Phase 1 and 2 clinical trials aimed at assessing the vaccine's safety, immunogenicity, and the duration of immunity induced by the QazCovid-in® vaccine after one or two immunisations. From 23.09.2020 to 19.03.2021 we performed a randomised, single-blind, placebo-controlled phase 1 clinical trial and from 18.10.2020 to 17.04.2021 an open-label phase 2 clinical trials of the QazCovid-in® vaccine with a 6 months follow-up at a single centre in Almaty, the Republic of Kazakhstan. Eligible healthy adults aged 18 years and older with no history of laboratory-confirmed SARS-CoV-2 infection were randomly assigned to the treatment groups using a computerised randomisation scheme generator. In the phase 1 clinical trial, two doses of the vaccine (5 μg each) or placebo (0·9% NaCl) were administered intramuscularly to 44 subjects aged 18–50 years, 21 days apart. In the phase 2 trial, 200 healthy participants were randomised into four equal-sized groups according to the age (18–49 or ≥50 years) and either single (day 1) or double (day 1 and 21) vaccination protocol. The primary outcomes were safety and tolerability. The secondary outcome was immunogenicity. The cellular response was measured by a whole-blood cytokine release assay (phase 1 only). The trials were registered with ClinicalTrials.gov NCT04530357. The QazCovid-in® vaccine was safe and well-tolerated and induced predominantly mild adverse events; no serious or severe adverse events were recorded in both trials. In the phase 1 trial, the percentage of subjects with a fourfold increase of antibody titres (sero conversion) in MNA was 59% after one vaccine dose and amounted to 100% after two doses. Neutralizing antibody titres reached the geometric mean titre (GMT) of 100 after administration of two doses. A statistically significant increase in the levels of pro-inflammatory cytokines after vaccination indicated the Th1-biased response. On day 180, 40% of placebo-treated subjects demonstrated a statistically significant increase in the levels of antibodies measured by both ELISA and MNA, which suggests the infection with SARS-CoV-2. In the phase 2 trial, 100% of subjects aged 18–49 years seroconverted for SARS-CoV-2 on day 21 after the first dose, as indicated by MNA yielding the GMTs of 32 or 30 in the one- and two-dose groups, respectively. Amongst ≥50-year-old subjects, the number of sero conversions in the two- and one-dose groups on day 21 was 94% and 92% with the respective GMTs of 25 and 24. After the second dose, the sero conversion rate reached 100%; however, the GMT was significantly lower when compared with the corresponding value measured in subjects aged 18–49 years (83 vs 143). In both trials, specific antibodies were detected in MNA and ELISA on study day 180, but the titres dropped in comparison to day 42. The results of this study serve as the rationale for the phase 3 study. The QazCovid-in® vaccine is safe and well-tolerated and promotes pronounced humoral immunity which lasts for at least 6 months after double intramuscular immunisation.

Tuberculosis is a major global threat to human health. Since the widely used BCG vaccine is poorly effective in adults, there is a demand for the development of a new type of boost tuberculosis vaccine. We designed a novel intranasal tuberculosis vaccine candidate, TB/FLU-04L, which is based on an attenuated influenza A virus vector encoding two mycobacterium antigens, Ag85A and ESAT-6. As tuberculosis is an airborne disease, the ability to induce mucosal immunity is one of the potential advantages of influenza vectors. Sequences of ESAT-6 and Ag85A antigens were inserted into the NS1 open reading frame of the influenza A virus to replace the deleted carboxyl part of the NS1 protein. The vector expressing chimeric NS1 protein appeared to be genetically stable and replication-deficient in mice and non-human primates. Intranasal immunization of C57BL/6 mice or cynomolgus macaques with the TB/FLU-04L vaccine candidate induced Mtb-specific Th1 immune response. Single TB/FLU-04L immunization in mice showed commensurate levels of protection in comparison to BCG and significantly increased the protective effect of BCG when applied in a “prime-boost” scheme. Our findings show that intranasal immunization with the TB/FLU-04L vaccine, which carries two mycobacterium antigens, is safe, and induces a protective immune response against virulent M. tuberculosis.

Background: The study was aimed at comparative evaluation of seasonal influenza vaccine RIBSP versus commercial vaccine VAXIGRIP® for immunogenicity and safety in the course of clinical trial phase II on healthy volunteers aged 18–60 years. Methods: The trial involved 150 subjects in randomized 2:1 groups that received either RIBSP vaccine or comparator vaccine VAXIGRIP®. One dose (0.5 ml) of either vaccine contained 15 μg of hemagglutinin of each influenza virus strain recommended by WHO for the Northern hemisphere in 2016–2017 flu season. The observation period lasted 21 day. The trial was registered at ClinicalTrials.gov identifier NCT 03016143. Results: Assessment of immunogenic activity of the vaccine under study showed that in 21 day the portion of participants with 4-fold seroconversions was 87.0% to A/H1N1; 63.0% to A/H3N2 and 59.0% to B virus. Antibody titer increase factor in the group of subjects that received RIBSP vaccine was 23.3 for A/H1N1; 4.4 for A/H3N2 and 4.5 for B virus. The volunteers that received RIBSP vaccine demonstrated 95% seroprotection level against A/H1N1; 84% against A/H3N2 and 80% against B virus. RIBSP vaccine met the CHMP criteria of the Committee for Medicinal Products for Human Use (CPMP/BWP/214/96). In the course of evaluating the vaccine safety no serious undesirable effects were recorded. All changes of laboratory data were slight and single in most cases. All recorded local reactions have been light in character and these have been predicted reactions observed at vaccination against influenza. Conclusion: Comparison of the allantoic inactivated split vaccine obtained in vaccines RIBSP and VAXIGRIP®, showed similar immunogenic activity. Both vaccines were safe for the study participants.

Background: The study was aimed at comparative evaluation of seasonal influenza vaccine RIBSP versus commercial vaccine VAXIGRIP® for immunogenicity and safety in the course of clinical trial phase II on healthy subjects up to 60 years. Methods: The trial involved 150 subjects in randomized 2:1 groups that received either RIBSP vaccine or comparator vaccine VAXIGRIP®. One dose (0.5 ml) of either vaccine contained 15 µg of hemagglutinin of each influenza virus strain recommended by WHO for the Northern hemisphere in 2016–2017 flu season. The observation period lasted 21 days. The trial was registered at ClinicalTrials.gov identifier NCT 03016143. Results: Assessment of immunogenic activity of the vaccine under study showed that in 21 days the portion of participants with 4-fold seroconversions was 80.0% to А/H1N1; 65.0% to А/H3N2 and 64.0% to B virus. Antibody titer increase factor in the group of subjects that received RIBSP vaccine was 13.4 for А/H1N1; 5.2 for А/H3N2 and 5.2 for B virus. The subjects that received RIBSP vaccine demonstrated 88% seroprotection rate against А/H1N1; 75% against А/H3N2 and 61% against B virus. In the course of evaluating the vaccine safety, no serious adverse events were recorded. All changes of laboratory data were slight and single in most cases. All recorded local reactions have been light in character and these have been predicted reactions observed at vaccination against influenza. Conclusion: Comparison vaccines RIBSP and VAXIGRIP®, showed similar immunogenic activity. The RIBSP vaccine is safe and immunogenic for the elderly and conforms to international criteria in CPMP/BWP/214/96.