Pre-Clinical Safety and Immunogenicity Study of a Coronavirus Protein-Based Subunit Vaccine for COVID-19.

Creating an effective and safe vaccine is critical to fighting the coronavirus infection successfully. Several types of COVID-19 vaccines exist, including inactivated, live attenuated, recombinant, synthetic peptide, virus-like particle-based, DNA and mRNA-based, and sub-unit vaccines containing purified immunogenic viral proteins. However, the scale and speed at which COVID-19 is spreading demonstrate a global public demand for an effective prophylaxis that must be supplied more. The developed products promise a bright future for SARS-CoV-2 prevention; however, evidence of safety and immunogenicity is mandatory before any vaccine can be produced. In this paper, we report on the results of our work examining the safety, toxicity, immunizing dose choice, and immunogenicity of QazCoVac-P, a Kazakhstan-made sub-unit vaccine for COVID-19. First, we looked into the product's safety profile by assessing its pyrogenicity in vaccinated rabbit models and using the LAL (limulus amebocyte lysate) test. We examined the vaccine's acute and sub-chronic toxicity on BALB/c mice and rats. The vaccine did not cause clinically significant toxicity-related changes or symptoms in our toxicity experiments. Finally, we performed a double immunization of mice, ferrets, Syrian hamsters, and rhesus macaques (Macaca mulatta). We used ELISA to measure antibody titers with the maximum mean geometric titer of antibodies in the animals' blood sera totaling approximately 8 log2. The results of this and other studies warrant recommending the QazCoVac-P vaccine for clinical trials.

Phylogenetic analysis of prospective M. bovis antigens with the aim of developing candidate vaccines for bovine tuberculosis.

BACKGROUND: Bovine Tuberculosis is a respiratory disease caused by the pathogen Mycobacterium bovis (M. bovis) that infects cattle. Though rare, this disease can also affect humans, as well as domestic and wild animals, making it a serious concern. Therefore, searching for alternative and new vaccines with high efficiency and safety is the main goal in bovine tuberculosis prophylaxis. New vaccines, known as vector vaccines, have the potential to become safe and effective alternatives to the traditional BCG vaccine. In this study, two major immunodominant proteins of M. bovis Esat-6 and TB10.4 were utilized to create a vector vaccine for bovine tuberculosis. METHODS: The Esat-6 and TB10.4 genes were amplified by PCR. The amplified and purified PCR products were sequenced by the Sanger method. Assembly and multiple alignments of amplicon nucleotides were carried out in the MEGA 11 software. RESULT: Two genes of the local strain 0078-M. bovis-8/RIBSP were sequenced. The nucleotide sequences were deposited in the GenBank database. Comparative analysis of the nucleotide sequences of the ESAT-6 and TB10.4 genes established 100% identity of the compared strains of Mycobacterium. CONCLUSION: Through the use of phylogenetic analysis, it has been confirmed that the amplified genes are related to the mycobacteria genus. This discovery allows the development of a vector vaccine against bovine tuberculosis utilising these genes.

Safety and Protective Efficacy of a Candidate Vector-Based Vaccine for Bovine Tuberculosis.

This study presents the results of a survey of the safety and protective efficacy of a candidate vector-based vaccine for bovine tuberculosis, using an influenza vector with the NS1 mutation and expressing M. bovis protective antigens ESAT-6 and TB10.4. We vaccinated Balb/c outbred mice two times at 21 days apart. Our experimental design includes mice immunised with the candidate vaccine with or without adjuvant 15% Montanide Gel. The candidate vaccine's safety was determined by biometric analysis, and protective efficacy was assessed by bacteriological and histological experiments following a virulent M. bovis-8 strain challenge. Our data indicated that the adjuvant-free version of the vaccine ensured complete protection from the M. bovis-8 infection in mice.

Safety and immunogenicity of the first Kazakh inactivated vaccine for COVID-19.

This article describes the results of a preclinical safety and immunogenicity study of QazCovid-in®, the first COVID-19 vaccine developed in Kazakhstan, on BALB/c mice, rats, ferrets, Syrian hamsters and rhesus macaques (Macaca mulatta). The study's safety data suggests that this immunobiological preparation can be technically considered a Class 5 nontoxic vaccine. The series of injections that were made did not produce any adverse effect or any change in the general condition of the model animals' health, while macroscopy and histology studies identified no changes in the internal organs of the BALB/c mice and rats. This study has demonstrated that a double immunization enhances the growth of antibody titers as assessed by the microneutralization assay (MNA) and the enzyme-linked immunosorbent assay (ELISA) in a pre-clinical immunogenicity test on animal models. The best GMT results were assessed in MNA and ELISA 7 days after re-vaccination; however, we noted that GMT antibody results in ELISA were lower than in MNA. A comparative GMT assessment after the first immunization and the re-immunization identified significant differences between model animal groups and a growth of GMT antibodies in all of them; also, differences between the gender groups were statistically significant. Moreover, the most marked MNA immune response to the QazCovid-in® vaccine was seen in the Syrian hamsters, while their SARS-CoV-2-specific antibody activity as assessed with ELISA was the lowest.

Development and Evaluation of a Live Attenuated Egg-Based Camelpox Vaccine.

Camelpox is an infectious viral disease of camels reported in all the camel-breeding areas of Africa, north of the equator, the Middle East and Asia. It causes huge economic loss to the camel industry. We developed a live camelpox virus vaccine candidate using an attenuated strain and evaluated its safety, immunogenicity and protective efficacy in camels. The attenuated virus strain was generated from the camelpox wild-type strain M-96 by 40 consecutive passages on the chorioallantoic membrane of 11-day-old embryonated chicken eggs, henceforth called KM-40 strain. Reversion to virulence of the KM-40 strain was evaluated in camels by three serial passages, confirmed its inability to revert to virulence and its overdose administration was also found safe. Studies of immunogenicity and protective efficacy of the candidate vaccine KM-40 strain in camels was carried out using the dose of 5 x 104.0 EID50. Our data showed complete protection against the challenge infection using the virulent wild-type camelpox virus strain M-96 (dose of 105.0 EID50) which was evaluated at 1, 3, 6 and 12 months post vaccination. In summary, our candidate live attenuated egg-based camelpox vaccine strain KM-40 was found safe, protective, and thus has the potential to use safely in field conditions.