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.

The most significant processes of arbovirus evolution can be expected to occur in the territories where ticks of different species cohabitate and at the boundaries of virus occurrence, where the probability of the appearance of new virus variants is high due to the possible shift in the main vectors and/or vertebrate hosts. One of the most interesting regions in this regard is the Republic of Tuva. Since most of its territory is covered by mountain ranges and intermountain basins, we were able to study the distribution of vectors and viruses in geographically isolated areas at different altitudes and in various landscapes. From 2008 to 2017, we conducted six expeditions to Tuva and collected 3,077 adult ticks and 24 nymphs. The distribution of tick species was confined to specific landscapes, as follows: Dermacentor nuttalli occurred in steppes, D. silvarum inhabited forest-steppe areas, and Ixodes persulcatus inhabited mixed forests. All three species of ticks were collected on plains and mountain slopes. The range of D. silvarum was shown to be lower than 1300 m above sea level (a.s.l.). Only D. nuttalli and I. persulcatus were collected at higher altitudes. According to our observations, single nymphs of D. nuttalli appear on animals one month before larvae appear. This finding confirms the hypothesis that the immature forms of D. nuttalli are able to overwinter under favourable conditions. We isolated 9 strains and 3 isolates of tick-borne encephalitis virus (TBEV) from I. persulcatus, one strain from D. nuttalli and one strain from D. silvarum. The TBEV strain from D. nuttalli was isolated from the territory inhabited only by Dermacentor ticks. All isolated strains belong to the Siberian subtype of TBEV. TBEV was detected in ticks from all the investigated altitudes. There were no statistically significant differences in the virus prevalence between the Dermacentor and Ixodes ticks. The results of our work provide additional support for the hypothesis of the existence of TBEV foci in areas with an absolute dominance of D. nuttalli.

Currently the only effective measure against tick-borne encephalitis (TBE) is vaccination. Despite the high efficacy of approved vaccines against TBE, rare cases of vaccine failures are well documented. Both host- and virus-related factors can account for such failures. In this work, we studied the influence of mouse strain and sex and the effects of cyclophosphamide-induced immunosuppression on the efficacy of an inactivated TBE vaccine. We also investigated how an increased proportion of non-infectious particles in the challenge TBE virus would affect the protectivity of the vaccine. The vaccine efficacy was assessed by mortality, morbidity, levels of viral RNA in the brain of surviving mice, and neutralizing antibody (NAb) titers against the vaccine strain and the challenge virus. Two-dose vaccination protected most animals against TBE symptoms and death, and protectivity depended on strain and sex of mice. Immunosuppression decreased the vaccine efficacy in a dose-dependent manner and changed the vaccine-induced NAb spectrum. The vaccination protected mice against TBE virus neuroinvasion and persistence. However, viral RNA was detected in the brain of some asymptomatic animals at 21 and 42 dpi. Challenge with TBE virus enriched with non-infectious particles led to lower NAb titers in vaccinated mice after the challenge but did not affect the protective efficacy.

Approximately 10,000 cases of tick-borne encephalitis (TBE), a serious disease of the central nervous system caused by tick-borne encephalitis virus (TBEV), are registered worldwide every year. Vaccination against TBE remains the most essential measure of preventing the disease. Unlike available TBE vaccines, a new inactivated lyophilized candidate vaccine Evervac is produced in Vero continuous cell culture and its final formulation does not include aluminum-based adjuvants. To study the safety and immunogenicity of Evervac, healthy adults 18–60 y of age were immunized twice at 30-d intervals. The study was single-blind, randomized, comparative, controlled, and was conducted in TBE-endemic areas. The commercial lyophilized vaccine TBE-Moscow was used as a comparison treatment. The subjects were observed for incidence, severity, and duration of adverse reactions. It was shown that the severity of local and systemic reactions in the Evervac vaccine group was mild to moderate. There were no significant differences in the incidence of adverse reactions between the Evervac and TBE-Moscow vaccine groups. Immunization with Evervac produced a significant increase in geometric mean titer (GMT) of anti-TBEV antibodies in both initially seronegative and seropositive recipients. The seroconversion rate for the initially seronegative recipients was 69% (GMT = 1:214) after the first dose and reached 100% after the second dose. In these parameters, there were no significant differences between the study and control vaccine groups. Thus, the adjuvant-free Vero-based vaccine Evervac was well tolerated, had low reactogenicity, induced a pronounced immune response, and was overall non-inferior to the commercial adjuvanted TBE vaccine used as a control.

This study aimed to estimate the impact of the COVID-19 pandemic on the circulation of non-SARS-CoV-2 respiratory viruses and the clinical characteristics of COVID-19 in hospitalized children. A total of 226 and 864 children admitted to the Children's City Clinical Hospital with acute respiratory infection in September to November of 2018 and 2020 in Moscow were tested for respiratory viruses using multiplex polymerase chain reaction (PCR) and Mycoplasma pneumoniae/Chlamydia pneumoniae using enzyme-linked immunosorbent assay. The detection rate of non-SARS-CoV-2 viruses in 2020 was lower than in 2018, 16.9% versus 37.6%. An increase in the median age of children with respiratory viruses was observed during the pandemic (3 years vs 1 year). There was no significant difference in the frequency of intensive care unit (ICU) admission in children with SARS-CoV-2 and other respiratory virus infections (2.7% vs 2.9%). SARS-CoV-2 and human rhinoviruses, human metapneumoviruses, and human adenoviruses showed significantly lower than expected co-detection rates during co-circulation. An increase in body mass index (BMI) or bacterial coinfection leads to an increased risk of ICU admission and a longer duration of COVID-19 in children. The COVID-19 pandemic led to significant changes in the epidemiological characteristics of non-SARS-CoV-2 respiratory viruses during the autumn peak of the 2020 pandemic, compared with the same period in 2018.