Vol 102, No 2 (2025)

Introduction. One of the more promising developments in preventing the spread of infections, including COVID-19, is the production of vaccines based on virus-like particles (VLP). Currently, in the National Research Center for Epidemiology and Microbiology named after N.F. Gamaleya of the Ministry of Health of the Russia has developed a VLP-based vaccine against COVID-19.

The aim of this study is to evaluate the tolerability, safety and immunogenicity of a new vaccine for the prevention of COVID–19 based on VLP compared with placebo for 21 days after two intramuscular injections in phase I clinical trials.

Materials and methods. A double-blind, placebo-controlled study of the tolerability, safety and immunogenicity of a vaccine for the prevention of COVID-19 based on VLP was conducted with a dose of the drug containing 40 and 80 micrograms of antigen, the placebo being 0.9% NaCl. The presence or absence of adverse events (AEs) after vaccination was noted in 180 volunteers aged 18 to 55 years; clinical and biochemical blood parameters, the intensity of humoral and cellular immunity before and after vaccination were assessed using enzyme immunoassay, neutralization reactions, lymphocyte blast transformation reactions and flow cytometry.

Results. An analysis of the tolerability and safety of the new COVID-19 VLP-vaccine showed that most adverse events were registered within the first 10 days after vaccination, mainly after the first vaccination. In the period from 11 to 21 days after vaccination, AEs were observed in isolated cases. No deaths, serious or other AEs have been reported. The administration of the studied vaccine to the volunteers had no negative effect on the basic vital signs. A comparative analysis of immunogenicity indicators in volunteers showed that the administration of a vaccine with both an antigen content of 40 µg and an antigen content of 80 µg leads to a pronounced and significant increase in the level of specific immunoglobulins, virus neutralizing antibodies and activation of a cell-mediated immune response. As part of the phase I clinical trials, a dose of 80 µg was selected as optimal.

Conclusion. It has been shown that a new vaccine for the prevention of COVID-19 based on VLP with an antigen content of 40 and 80 µg when administered intramuscularly to volunteers does not cause serious adverse events and induces a tense humoral and cellular immune response.

Introduction. Whooping cough remains an urgent health problem worldwide, including in countries with high vaccination rates, where, since the 1990s, there has been an increase in the incidence of whooping cough, an increase in the severity of the disease and mortality. In this situation, it is necessary to create a new generation of acellular pertussis vaccines (аPV) that can more effectively affect the colonization, persistence and transmission of Bordetella pertussis. One of the possible directions for improving the vaccine prophylaxis of pertussis infection is the creation of aPV based on protective antigens isolated from biofilm cultures of B. pertussis.

The aim of the study was to research the level of IgG antibodies to the antigens of the pertussis pathogen: adhesins — filamentous hemagglutinin (FHA), pertactin (PRN) and toxins — pertussis toxin (PT), lipopolysaccharide (LPS) in mice immunized with experimental aPV based on antigenic complexes (AC) isolated from biofilm and planktonic cultures of B. pertussis.

Materials and methods. Experimental aPV based on AC isolated from the culture medium of biofilm (aPV-B) and planktonic (aPV-P) cultures of B. pertussis strain No. 317 (serotype 1.2.3) were used in the experiments. IgG titers of antibodies to PT, FHA, PRN and LPS in blood sera of mice immunized with aPV-B and aPV-P was determined in ELISA.

Results. The titers of IgG antibodies to adhesins (FHA and PRN) in the aPV-B group were 8 and 4 times higher, respectively, compared with aPV-P, in the absence of significant differences in the titers of IgG antibodies to PT and LPS.

Conclusion. The higher ability of aPV-B to induce an immune response to B. pertussis adhesins compared to aPV-P, in the absence of significant differences between them in stimulating IgG antibodies to toxins, indicates the advantage of using antigenic complexes from biofilm cultures to create aPV of a new type.

Introduction. The Kirov region is an endemic region for Lyme disease (ixodic tick-borne borreliosis), which is caused by climatic conditions, an abundance of ticks and their feeders. The economic damage caused by Lyme disease includes the cost of treating patients and eliminating natural foci. Morbidity forecasting is necessary for planning preventive measures (acaricide treatments, awareness-raising activities with the population) and entomological monitoring. The effectiveness of such measures exceeds the above costs, which underlines the relevance of the study.

The aim of the study is to analyze the influence of various factors on the incidence of Lyme disease using mathematical modeling methods for further epidemiological forecasting using the example of the Kirov region.

Materials and methods. The data of the state reports «On the state of sanitary and epidemiological welfare of the population in the Kirov region» for 2006–2023 on the incidence of Lyme disease, the first and last reported cases of tick attachment to humans and the volume of acaricide treatments were studied. Hydrometeorological data: monthly and annual averages of air temperature, humidity, and precipitation. Spearman correlation analysis and multiple regression analysis were performed using the «Excel MS Office-2021» and «Statistica Advanced 12 for Windows RU» software. The level of p < 0.05 was chosen as a criterion of statistical significance.

Results. The interval forecast of incidence is up to 18.67 by 2024, 16.51 by 2025, and 14.36 per 100,000 population by 2026. Correlations between climatic factors and morbidity have been identified. A negative reliable correlation of moderate density was revealed between the incidence of Lyme disease in the Kirov region and the volume of acaricide treatments. Two forecasting models have been developed: based on the timing of the first and last reported cases of tick bites; based on hydrometeorological factors and the volume of acaricide treatment.

Conclusion. The incidence of Lyme disease in the Kirov region is characterized by a downward trend. Mathematical models for predicting morbidity in the Kirov region are proposed.

Introduction. Metagenomic sequencing is one of the most promising methods for both the detection and identification of natural focal infection (NFI) pathogens and for determining the species composition of various bacterial communities.

The aim is to detect and identify the NFI pathogens in samples of field and clinical material using metagenomic sequencing of 16S rRNA gene fragments, and to analyze the taxonomic composition of endosymbiotic microorganisms in the samples.

Materials and methods. Samples of field (14 samples) and clinical (2 samples) material with varying loads of DNA from NFI pathogens, determined by PCR (Borrelia burgdorferi sensu lato, Anaplasma phagocytophilum, Francisella tularensis, Rickettsia spp., Coxiella burnetii), were investigated. Amplification of fragments of the gene encoding 16S rRNA was performed using primers flanking the variable regions of the gene.

Results. In 14 out of 16 studied samples, target NFI pathogens were detected. The species identified included R. aeschlimannii (in 57.1% of positive samples), B. valaisiana (in 16.6%), F. tularensis (in 75%), C. burnetii (in 100%), and borreliae — pathogens of relapsing fevers (B. turcica, B. hispanica) were also found in one sample. The taxonomic structure of the microbiome of Ixodes ricinus, Dermacentor reticulatus, Rhipicephalus annulatus, Hyalomma aegyptium, Dermacentor marginatus ticks collected in the southern regions of the Russian Federation was studied. It was shown that the predominant microorganisms are representatives of the genera Flavobacterium, Pseudomonas, Serratia, Aeromonas, Pedobacter, Bradyrhizobium, Shingomonas. DNA markers of microorganisms — endosymbionts of ticks Candidatus Midichloria mitochondrii, representatives of the genera Rickettsiella, Coxiella, non-pathogenic and conditionally pathogenic species of the genus Francisella were found in pools of Ixodes ticks.

Conclusion. The effectiveness of the method of metagenomic sequencing of fragments of the 16S rRNA gene for the detection and identification of NFI pathogens in samples of clinical and field material was demonstrated. Metagenomic sequencing of 16S rRNA gene regions can be recommended as an additional laboratory method for detecting and identifying NFI pathogens.

Oncological diseases remain the main cause of death and disability of the population worldwide. The most malignant types of cancer include of pancreas, liver and brain tumors. Modern methods of therapy (including chemoradiation, targeted and immune therapy) do not allow achieving the desired effectiveness in this group of patients. In this regard, new approaches to the treatment of oncological diseases are needed.

The aim of this review was to discuss the mechanisms of anticancer action of Strepococcus pyogenes and other streptococcal species, as well as to consider their cancer-stimulating effects and their limitations.

The review considers the current state of the problem of using bacterial oncotherapy involving streptococci A group (in particular, S. pyogenes). The involvement of S. pyogenes pathogenicity factors is discussed: M-protein, exotoxins: streptolysins S, O, superantigens, arginine deiminase, etc., as well as molecular mechanisms mediated by the host immune system cells. The authors' own data show that S. pyogenes exhibits selective M-protein-mediated cytolytic activity against C6 glioma and pancreatic adenocarcinoma (Panc) tumor cells and no activity against normal fibroblasts. The data on preclinical and clinical application of the streptococcal-based medicine OK-432 for the therapy of oncological diseases are briefly summarized. Tumor-associated properties of streptococci (induction of cytokine storm, proliferation, migration and angiogenesis of vascular epithelial cells, formation of neutrophil extracellular traps in the tumor microenvironment) caused by their interaction with immune cells of the tumor-bearing organism are also discussed.

Conclusion. The research data presented in this review convincingly demonstrate that S. pyogenes, with the participation of pathogenicity factors, can directly exert an antitumor effect on cancer cells. However, it should be noted the streptococcal vaccine should be used with caution, taking into account the individual characteristics of the patient's immune system, since S. pyogenes can also have effects of the opposite nature, requiring further research.

Respiratory syncytial virus (RSV) is the leading cause of upper respiratory tract infections in children and the elderly. The only specific treatment approved for RSV is the monoclonal antibody Palivizumab for passive immunoprophylaxis in high-risk infants. Sixty years after the virus was discovered, several safe RSV vaccine candidates have been licensed. This was facilitated by research to identify the structure of RSV, to study the basic functions of RSV components as well as the mechanisms of innate and acquired immune responses to infection. The negative result of a clinical trial of formalin-inactivated RSV vaccine in children, which resulted in the death of several vaccinated individuals, was taken into account.

The aim of the study was to summarize data from studies of RSV vaccine candidates in laboratory animals and in clinical trials on different age groups.

Articles for the analysis of preclinical and clinical trials of RSV vaccines were found, using the PubMed search engine with “respiratory syncytial virus and vaccine” as the keywords. The selection criteria were that original articles should contain information on preclinical and clinical studies, the latter including phase I–IV randomized controlled trials. From 1967 to the present year, 296 articles summarizing data from studies of RSV vaccine candidates and 1788 articles summarizing data from animal trials of vaccine candidates were found. The review summarizes data from preclinical studies of vaccine candidates and their developers, vaccine formulations, animal models on which the studies were conducted, as well as a brief description of the main findings. Data on clinical trials of vaccine candidates are presented, including target populations, clinical trial number and sources where the results of these trials were published.