Vol 99, No 5 (2022)

Introduction. Rubella is a mild infectious disease affecting mainly children and is caused by the rubella virus, part of the Matonoviridae family, genus Rubivirus. Rubella causes congenital rubella syndrome (CRS) and is the main cause of developmental abnormalities, especially blindness and deafness.

There is no specific treatment for rubella and CRS. In order to avoid possible complications from rubella infection, a live attenuated rubella vaccine based on the foreign strain of Wistar RA 27/3 rubella virus is used. However, the actual, more effective and preferred vaccine strain the rubella virus for the Russian Federation is considered to be a viral strain of rubella circulating on its territory.

The aim of the study was to study the biological properties of the developed domestic cold-adapted strain vRub-Ant circulating in the territory of the Russian Federation.

Materials and methods. Following cell cultures were used in the study — human embryo lung diploid cell strain LECH-3, transferable cell line from embryonic kidney cells of green monkeys Vero CCL-81 and Vero ECC, human mesenchymal stem cells, human peripheral blood mononuclear cells (PBMC). Cell cultures were grown on a DMEM/F12 nutrient medium with the addition of 5% fetal bovine serum. Swabs from the pharynx and nasal passages from a child with rubella were used as clinical virus-containing material. Monoclonal anti-idiotypic antibodies m(anti-ID)Ab were used to assess the expression level of alpha/beta and gamma interferon receptors (α/β and γIFN-R)Ab, imitating the biological effects of alpha/beta and gamma interferons (α/β and γIFN) of humans. The cultural, virological, immunochemical and serological research methods were applied in the study.

Results. Attenuation of the vRub-Ant clinical isolate of rubella virus was carried out for 20 consecutive passages on LECH-3 diploid cells at a reduced temperature of 30°C. The main biological markers of attenuation were determined to be ts and ca phenotypes. The avirulence of the attenuated viral strain (att-phenotype) was assessed by the level of expression of α/β and γIFN-R. A lower level of α/β and γIFN-R expression was found on the membranes of human PBMC induced by the vaccine strain vRub-Ant in comparison with the parent wild variant of the rubella virus. This trait,the att phenotype, is characteristic of attenuated viral strains. It has been shown that the vaccine strain vRub-Ant has lost neurotropism and was unable to bind to the membrane receptors of the brain (MRB) of guinea pig embryos, unlike its parent rubella virus strain. The high immunogenicity of the domestic cold-adapted strain vRub-Ant was confirmed by high titers of neutralizing rubella antibodies observed in guinea pigs immunized subcutaneously with one vaccination dose of the virus.

Conclusion. A domestic attenuated vaccine strain vRub-Ant of the rubella virus that has the main biological markers of attenuation (ts-ca and att phenotypes) has been developed. The vaccine strain vRub-Ant induces a high levels of neutralizing antibodies in guinea pigs following the immunization with a single vaccination dose of the vaccine. The viral strain vRub-Ant has lost its tropism to the MRB of guinea pig embryos, unlike its parent variant.

Background. Children and adolescents with infection caused by the hepatitis C virus (HCV) have not been given sufficient attention due to mild forms of HCV and delays in approval of antiviral treatment regimens. Omissions in the studies of pediatric cohorts and shortcomings of management policies aimed at children should be eliminated by improving screening coverage and access to treatment.

The aim of the study was to present the results of the cascade sequence of diagnostic testing, care and treatment of children with HCV in the Moscow Region (MR).

Materials and methods. The study included all HCV seropositive children of MR (n = 175), who underwent screening tests, and it did not include patients living with HIV/HCV coinfection. Children were observed from 2017 to 2022. The HCV RNA was detected in 164 children and HCV genotypes were identified in 99 children. The stage of liver fibrosis was assessed in 73 children by transient elastography and by FIB-4 index calculation.

Results. In MR, 93.7% of seropositive children were tested for HCV RNA; 71.2% of adolescents over 12 years of age received treatment. The prevalence of HCV seropositivity was estimated at 0.113/1,000 children population; the prevalence of chronic HCV infection was at least 0.059/1,000. The dominant HCV subtypes were GT 1b (43.4% [the 95% confidence interval, 33.5–53.8%]), GT 3a (23.2% [15.3–32.8%]) and GT 3a/3b (20.2% [12.8–29.5%]). The incidence of viremic HCV infection per 100,000 children was 3.3 among children under 3 years of age; 7.0 – among children aged 3–6 years; 7.7 – among children aged 7–11 years, 4.4 – among adolescents older than 12 years. Natural HCV clearance was reported at the frequency of 19.5% [13.8–26.4%]. Extrahepatic manifestations were of rare occasion – 2.9% [0.9–6.5%]. Vertical transmission was the primary route of HCV transmission (78.3% [71.4–84.2%]); infection is assumed to occur during medical invasive procedures — 7.4% [4.0–12.4%], drug using — 0.6% [0.01–3.10%], in the family household – 0.6% [0.01–3.10%]. New cases of HCV infection were more frequently detected during routine examination of children prior to hospitalization or children born to mothers with HCV. Viremic HCV was confirmed in 90.2% [84.6–94.3%], including HCV infection – in 53.4% [45.0–61.6%], chronic liver disease – in 35.8% [28.1–44.1%] having low activity and occasional consequences (the fibrosis METAVIR score of F1 and F1-2 – 17.8% [9.8–28.5%]). No significant clinical and epidemiological differences between the natural course of chronic HCV infection and the liver disease caused by HCV have been found. The burden of pediatric HCV in MR is aggravated by a significant proportion of socially vulnerable patients and patients with comorbid conditions.

Conclusion. One of the solutions for detection of new pediatric cases of HCV infection in MR can be offered by improvement of collaboration and continuity of care among healthcare organizations and early treatment of women of childbearing age. Further research is required to evaluate the effectiveness of routine testing of all socially vulnerable pediatric groups. Early application of pan-genotypic antiviral treatment regimens can contribute significantly to control of the HCV infection incidence in children.

Aim. Study the effect of trypsin, lidase (hyaluronidase) and fluimucil (N-acetyl-L-cysteine) on the growth of biofilms of Bordetella pertussis strains on the abiotic substrate.

Materials and methods. In the experiments, the strains of the main B. pertussis serotypes isolated in the Russian Federation from whooping cough patients in 2001–2010 were used: No. 178 (serotype 1.2.0), No. 287 (serotype 1.0.3) and No. 317 (serotype 1.2.3), grown on a dense nutrient medium. The intensity of biofilm formation in a liquid nutrient medium in the presence of trypsin, lidase and fluimucil in round-bottomed polystyrene 96-well plates was estimated by staining with 0.1% gentian-violet solution.

Results. Trypsin suppressed the growth of biofilms and destroyed the formed biofilms. Lidase suppressed the growth of biofilms less actively, without affecting the formed biofilms. Fluimucil did not affect both the growth of biofilms and the formed biofilms. The growth of colonies typical for B. pertussis was noted when planting fluids from cultures in the presence of preparations, as well as from culture control wells on a dense nutrient medium.

Conclusion. The different effect of the drugs studied by us may be related to the different quantitative content of targets for trypsin (proteins), lidase (mucopolysaccharides, containing uronic acids), fluimucil (acid mucopolysaccharides) in the biofilm matrix. The growth of the typical morphological properties of the colony of B. pertussis during the sowing of culture seedlings on a dense nutrient medium testifies to the destruction of the biofilm matrix by trypsin and lidase in the absence of influence on plankton cells.

The aim of study was to carry out comparative investigation of biological properties of site-specific mutants of Influenza A virus and variant of live cold-adapted (CA) influenza reassortant vaccine.

Materials and methods. The genetic stability of site-specific mutants (SSM) of the A/WSN/33 (H1N1) strain with ts (temperature sensitive)-mutations in polymerase genes was studied using a stress-test in Madin–Darby Canine Kidney (MDCK) culture. A comparative study of immunogenicity of U2 and M26 mutants with the high genetic stability and the CA-reassortant with similar surface proteins was carried out. The increase in the antibody titer was investigated using enzyme-linked immunosorbent assay and the reaction of delayed hemagglutination. Ability of the studied viruses to induce type 1 interferon in A549 cells was determined using real-time polymerase chain reaction (real-time PCR).

Results. It was shown that U2 and M26 mutants, which have 3 ts-mutations or more in polymerase genes have high genetic stability. It was found that U2 and M26 mutants induced a higher antibody titers than the CA reassortant in mice following the intranasal immunization. The ability of site-specific mutants and CA reassortant to induce type 1 interferon was also investigated. Mutants U2 and M26 increased the level of interferon to a greater extent than the CA-reassortant.

Conclusion. The data obtained indicate that SSM U2 and M26 with 3 ts-mutations or more in the genome have a significant level of genetic stability. Mutants U2 and M26 have a higher immunogenicity and a higher ability to induce interferon in comparison with the CA reassortant. These facts allow us to conclude that SSM of the influenza virus with a set of mutations in polymerase genes can be considered as promising candidates for live influenza vaccines.

Introduction. The prevalence of Streptococcus pneumoniae strains causing invasive forms of pneumococcal infection and the growing rates of antibiotic resistance of individual serotypes of the pathogen pose a number of urgent and socially significant tasks the search for new antimicrobial agents for prevention and treatment.

Objective. To analyze the data of scientific publications of domestic and foreign authors on the problems of practical use and prospects for the development of the bacteriophage S. pneumoniae drug aimed at the actual serotypes of the pathogen.

Results. Analysis of literary sources in scientific electronic databases and publishing houses eLibrary.Ru, ScienceDirect, Scopus, PubMed, Springerlink, Wiley Online Library, Annual reviews allowed us to summarize information about four isolated lytic bacteriophages of S. pneumoniae and their endolysins, as well as about two lysogenic phages, to present data on the clinical efficacy of streptococcal bacteriophage in pneumococcal infection in animals and humans. The results of search queries on the most significant and widespread serotypes of S. pneumoniae in the territory of the Russian Federation have established the predominance in the structure of variants 19F, 14, 9V/A, 15 A/F, 6 A/B/C/D, 3 and 23F. Some of them are characterized by a high level of antibiotic resistance and cause invasive forms of the disease, and serotypes 15 A/F/C, 6 C/D are not represented in modern vaccines, which increases the relevance of the development and use of pneumococcal bacteriophage, including intraspecific typing of significant and common serotypes.

Conclusion. Based on the analysis of the current state of the issue of pneumococcal bacteriophages, the information obtained on the circulation of topical strains of S. pneumoniae on the territory of the Russian Federation and their serotype landscape, it is concluded that the development of the bacteriophage S. pneumoniae drug is relevant as a means of targeted action for the prevention, diagnosis and personalized therapy of human diseases of pneumococcal etiology.

Understanding the entire pathogenesis of HIV infection, from penetration at the gates of infection to the induction of severe immunodeficiency, is an essential tool for the development of new treatment methods. Less than 40 years of research into the mechanisms of HIV infection that lead to the development of acquired immunodeficiency syndrome have accumulated a huge amount of information, but HIV's own unique variability identifies new whitespaces.

Despite the constant improvement of the protocols of antiretroviral therapy and the success of its use, it has not yet been possible to stop the spread of HIV infection. The development of new protocols and the testing of new groups of antiretroviral drugs is possible, first of all, due to the improvement of animal models of the HIV infection pathogenesis. Their relevance, undoubtedly increases, but still depends on specific research tasks, since none of the in vivo models can comprehensively simulate the mechanism of the infection pathology in humans which leads to multi-organ damage.

The aim of the review was to provide up-to-date information on known animal models of HIV infection, focusing on the method of their infection and anatomical, physiological and pathological features.