Breaking the Barrier: SARS-CoV-2 Infections in Wild and Companion Animals and Their Implications for Public Health.

The emergence of the novel coronavirus SARS-CoV-2 has led to significant interest in its potential transmission between animals and humans, especially pets. This review article summarises the literature on coronavirus infections in domestic animals, emphasising epidemiology, transmission dynamics, clinical manifestations, and public health implications. This article highlights current understandings of the relationship between infections in companion animals and humans, identifies research gaps, and suggests directions for future research. Cases of disease in cats, dogs, and other domestic animals, often occurring through close contact with infected owners, are reviewed, raising concerns about possible zoonotic and reverse zoonotic transmission. Precautions and recommendations for pet owners and healthcare workers are also discussed. The scientific evidence presented in the article highlights the need for a One Health approach that considers the health of people, animals, and the environment to combat future pandemics.

Field Trials of Live and Inactivated Camelpox Vaccines in Kazakhstan.

An outbreak of camelpox occurred in the Mangistau region of Kazakhstan in 2019. To control the outbreak of camelpox and to prevent its further spread to other regions, camels were vaccinated using live and inactivated camelpox vaccines produced in Kazakhstan. To evaluate the efficacy of these camelpox vaccines in the field, vaccine trials used 172 camels on camel farms in the Beineu district. Of these, 132 camels were vaccinated using a live attenuated camelpox vaccine and 40 camels were vaccinated using an inactivated vaccine to observe immunogenicity and safety. The live vaccine was inoculated into camels by scarification at a dose of 5 × 104 EID50, and the inactivated vaccine was injected intramuscularly at 5 mL twice, with an interval of 35 days. During the safety evaluation, camels administered either vaccine displayed no clinical signs of illness or any adverse effects. Post-vaccination seroconversion demonstrated that the live attenuated vaccine started to elicit antibody responses in some animals as early as day seven, while, by day 28, 99% of vaccinated camels responded. For camels immunized with the inactivated vaccine, seroconversion began on day 21 at low titers ranging from 1:2 to 1:4. Ninety days post vaccination, 77% of the camels demonstrated an immune response that was up to a titer of 1:16. The antibody response waned six months post vaccination in camels vaccinated with two types of vaccine. Nonetheless, both vaccines were 100% effective at preventing clinical disease in vaccinated camels during the camelpox outbreak. All unvaccinated camels became ill, with manifestations of clinical signs characteristic of camelpox. Following these successful field trials in Kazakhstan, a vaccination program for camels, to control camelpox using the domestically produced live attenuated camelpox vaccine, has started.

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.

Assessment of Peste des Petits Ruminants Antibodies in Vaccinated Pregnant Ewes of Kazakh Breed Fine-Fleeced and Determination of the Decreasing Trend of Maternal Immunity in Their Lambs.

In this article, we first assessed peste des petits ruminants (PPR) antibodies in vaccinated pregnant ewes of Kazakh breed fine-fleeced immunized with the PPR vaccine and the duration of maternal immunity in their lambs. Ewes in the last trimester of pregnancy and gestation were immunized with a vaccine from the Nigeria 75/1 strain of the PPR virus (PPRV) produced by the Research Institute of Biological Safety Problems (RIBSP), Kazakhstan. Serum samples from lambs born from vaccinated and unvaccinated ewes were collected a week after birth and at intervals of 7 days for 18 weeks after birth. Serum samples collected from lambs were tested for PPR antibodies using competitive ELISA and virus neutralization test (VNT). Maternal antibodies (MAs) in lambs born from vaccinated ewes were detected for up to 18 weeks, with a tendency to decrease starting at week 14, and by the end of the experiment receded below the protective level (<1:8). In the blood serum of a 14-week-old lamb with MAs (1:8), post vaccination with a field dose (103 TCID50) of the vaccine against PPR, the titers of protective antibodies against PPRV increased to 1:16 on day 14 post vaccination, and the lamb was protected from infection with the field PPRV. A lamb of the same age with MAs in the 1:8 titer was 100% protected from infection with the field PPRV. Therefore, it is recommended that lambs of the Kazakh fine-wool breed be immunized from the age of 14 weeks or older to avoid a period of susceptibility.

Coding Complete Genome Sequence of the SARS-CoV-2 Virus Strain, Variant B.1.1, Sampled from Kazakhstan.

This article describes the results of sequencing and analysis of the entire genome of the SARS-CoV-2 virus sampled in Kazakhstan in 2021. The whole-genome sequence of the strain was 29,751 bp. According to the results of phylogenetic analysis (according to the Pangolin COVID-19 database), the SARS-CoV-2/human/KAZ/B1.1/2021 strain studied here was assigned to variant B.1.1.

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

This research describes the genome sequence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) obtained from a patient with symptoms of coronavirus disease 2019 (COVID-19) who was infected in the Republic of Kazakhstan. Strain SARS-CoV-2/human/KAZ/Britain/2021 consists of 29,815 nucleotides and belongs to lineage B.1.1.7, according to the Pangolin COVID-19 database.

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.

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.

Background: Vaccination remains the primary measure to prevent the spread of the SARS-CoV-2 virus, further necessitating the use of effective licensed vaccines. Methods: From Dec 25, 2020, to July 11, 2021, we conducted a multicenter, randomised, single-blind, placebo-controlled phase 3 efficacy trial of the QazCovid-in® vaccine with a 180-day follow-up period in three clinical centres in Kazakhstan. A total of 3000 eligible participants aged 18 years or older were randomly assigned (4:1) to receive two doses of the vaccine (5 µg each, 21 days apart) or placebo administered intramuscularly. QazCovid-in® is a whole-virion formaldehyde-inactivated anti-COVID-19 vaccine, adjuvanted with aluminium hydroxide. The primary endpoint was the incidence of symptomatic cases of the SARS-CoV-2 infection confirmed by RT-PCR starting from day 14 after the first immunisation. The trial was registered with ClinicalTrials.gov NCT04691908. Findings: The QazCovid-in® vaccine was safe over the 6-month monitoring period after two intramuscular immunisations inducing only local short-lived adverse events. The concomitant diseases of participants did not affect the vaccine safety. Out of 2400 vaccinated participants, 31 were diagnosed with COVID-19; 43 COVID-19 cases were recorded in 600 placebo participants with onset of 14 days after the first dose within the 180-day observation period. Only one severe COVID-19 case was identified in a vaccine recipient with a comorbid chronic heart failure. The protective efficacy of the QazCovid-in® vaccine reached 82·0% (95% CI 71.1-88.5) within the 180-day observation period. Interpretation: Two immunisations with the inactivated QazCovid-in® vaccine achieved 82·0% (95% CI 71.1-88.5) protective efficacy against COVID-19 within a 180-day follow-up period. Funding: The work was funded by the Science Committee of the Ministry of Education and Science of Kazakhstan within the framework of the Scientific and Technical Program "Development of a vaccine against coronavirus infection COVID-19". State registration number 0.0927.

Serological exposure in Bactrian and dromedary camels in Kazakhstan to a MERS or MERS-like coronavirus.

Middle East Respiratory Syndrome Coronavirus (MERS-CoV) is a camel-borne zoonotic virus endemic across Eastern Africa and the Middle East, with evidence of circulation in Bangladesh and Mongolia. To determine if MERS-CoV was present in Kazakhstan, in 2017-2018, we collected swabs and sera from Bactrian camels (n = 3124) and dromedary (n = 5083). The total seropositivity was 0.54% in Bactrian camels and 0.24% in dromedaries; however, we did not detect MERS-CoV RNA in swab samples. There was no difference in the probability of infection between species or sex, but younger camels had a higher probability of being seropositive, suggesting a recent introduction of the virus to Kazakhstan. The infection of both camel species indicates that they both may play a role as natural reservoirs. These results reinforce the need for continual surveillance, especially at the camel-human interface to understand the risk of zoonotic exposure.

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

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.

Discovery and Characterization of Novel Bat Coronavirus Lineages from Kazakhstan.

Coronaviruses are positive-stranded RNA viruses that infect a variety of hosts, resulting in a range of symptoms from gastrointestinal illness to respiratory distress. Bats are reservoirs for a high diversity of coronaviruses, and focused surveillance detected several strains genetically similar to MERS-coronavirus, SARS-coronavirus, and the human coronaviruses 229E and NL63. The bat fauna of central Asia, which link China to eastern Europe, are relatively less studied than other regions of the world. Kazakhstan is the world's ninth largest country; however, little is understood about the prevalence and diversity of bat-borne viruses. In this study, bat guano was collected from bat caves in three different sites of southern Kazakhstan that tested positive for coronaviruses. Our phylogenetic reconstruction indicates these are novel bat coronaviruses that belong to the genus Alphacoronavirus. In addition, two distinct lineages of Kazakhstan bat coronaviruses were detected. Both lineages are closely related to bat coronaviruses from China, France, Spain, and South Africa, suggesting that co-circulation of coronaviruses is common in multiple bat species with overlapping geographical distributions. Our study highlights the need for collaborative efforts in understudied countries to increase integrated surveillance capabilities toward better monitoring and detection of infectious diseases.

Saigas on the brink: Multidisciplinary analysis of the factors influencing mass mortality events.

In 2015, more than 200,000 saiga antelopes died in 3 weeks in central Kazakhstan. The proximate cause of death is confirmed as hemorrhagic septicemia caused by the bacterium Pasteurella multocida type B, based on multiple strands of evidence. Statistical modeling suggests that there was unusually high relative humidity and temperature in the days leading up to the mortality event; temperature and humidity anomalies were also observed in two previous similar events in the same region. The modeled influence of environmental covariates is consistent with known drivers of hemorrhagic septicemia. Given the saiga population's vulnerability to mass mortality and the likely exacerbation of climate-related and environmental stressors in the future, management of risks to population viability such as poaching and viral livestock disease is urgently needed, as well as robust ongoing veterinary surveillance. A multidisciplinary approach is needed to research mass mortality events under rapid environmental change.