Search

This study examines the process of evacuating Soviet automotive industry enterprises during the Great Patriotic War using the example of the Moscow Automobile Plant named after I. V. Stalin. The relevance of the research is justified by the necessity to reconstruct the activities of the highest bodies of party-state management during the industrial evacuation. Archive documents of the Evacuation Council under the People’s Commissariat of the USSR were analyzed. The Council operated from June to December 1941 as a commission under the Soviet government and was responsible for evacuating enterprises and institutions. The sources of the study were documents of the State Defense Committee of the USSR, the highest body of party-state power in the country during the Great Patriotic War. Correspondence between the plant management and various institutions and departments, as well as evacuation reports, were used as research materials. The existing evacuation options for of the Moscow Automobile Plant named after I. V. Stalin, discussions among Soviet agencies on the location of the plant in rear areas of the country were examined. Based on statistical summaries and reports, the intensity of the evacuation process and its outcomes were studied. It is concluded that the evacuation of the Moscow Automobile Plant named after I. V. Stalin contributed to preserving the country’s industrial potential and had a long-term positive impact on the development of the Soviet automotive industry.

Scientific relevance. The use of recombinant antigens in vaccine production is limited because vaccines based on such antigens tend to have low immunogenicity. However, a COVID-19 vaccine that combines recombinant SARS-CoV-2 spike glycoprotein as its antigen and virus-like immune-stimulating complexes (ISCOMs) as its adjuvant (Nuvaxovid) induces a protective virus-neutralising response. The State Research Center of Virology and Biotechnology “Vector” (hereinafter, Vector) has developed the ISCOM adjuvant Matrix-V, which plays a key role in inducing virus-neutralising antibodies. Studying Matrix-V will provide for the wide use of recombinant antigens combined with this adjuvant in the development and production of novel Russian vaccines.Aim. This study aimed to evaluate the humoral immune responses of experimental animals to intramuscular injections of a complex combining the recombinant Wuhan-type SARS-CoV-2 spike RBD antigen and the virus-like ISCOM adjuvant containing Quillaja saponaria saponins.Materials and methods. The Matrix-V ISCOM adjuvant was produced using Vector’s proprietary technology, which involves cross-flow filtration through Sartorius VivaFlow cassettes. To determine the saponin and residual detergent concentrations in Matrix-V, the authors conducted high-performance liquid chromatography. Having produced the recombinant SARS-CoV-2 RBD antigen, the authors used electron microscopy to analyse the ultrastructure of the ISCOM–antigen complex. In the study of the ISCOM–antigen complex, 25 female Balb/c mice (5 groups) and 15 male and female outbred guinea pigs (3 groups) received two intramuscular injections with a 14-day interval. Serum tests relied on virus neutralisation (VN) and enzyme-linked immunosorbent assay (ELISA) methods and used antigens of 8 SARS-CoV-2 variants (State Collection of Viruses and Rickettsia, Vector). The authors used Statistica 10 to analyse the results.Results. Two injections of the SARS-CoV-2 RBD antigen (mice: 7 μg, guinea pigs: 1 μg) alone did not induce statistically significant virus-neutralising antibody responses, as shown by the VN results. Two injections of the SARS-CoV-2 RBD antigen (mice: 7 μg, guinea pigs: 1 μg) adjuvanted with Matrix-V (25 μg) resulted in geometric mean antibody titres of 1:83–1:178 (mice) and 1:174–1:587 (guinea pigs) in the VN tests with the Wuhan variant. One injection of the antigen (1 μg or 7 μg) with Matrix-V (25 μg) induced antibodies only in individual cases, as demonstrated by the VN and/or ELISA results. The most intensive immune response was observed in ELISA tests with the Delta variant after two injections of the Ecto-S-Wuhan (1 μg) and Matrix-V (25 μg) complex. Immune responses did not differ between the group that received two injections of the Ecto-S-Wuhan antigen (1 μg) without the ISCOM adjuvant and the negative control group (titres below 1:100; p=0.95). Two injections of the SARS-CoV-2 RBD antigen (7 μg) without the ISCOM adjuvant induced antibodies in mice (titres between 1:248 and 1:1477).Conclusions. Two intramuscular injections of the complex containing the recombinant SARS-CoV-2 RBD antigen and the Matrix-V ISCOM adjuvant induce virus-neutralising antibodies. The approach proposed by the authors has the potential for use in the development of immunobiological medicinal products to prevent and treat a wide range of infectious diseases.

The monkeypox epidemic, which became unusually widespread among humans in 2022, has brought awareness about the necessity of smallpox vaccination of patients in the risk groups. The modern smallpox vaccine variants are introduced either intramuscularly or by skin scarification. Intramuscular vaccination cannot elicit an active immune response, since tissues at the vaccination site are immunologically poor. Skin has evolved into an immunologically important organ in mammals; therefore, intradermal delivery of a vaccine can ensure reliable protective immunity. Historically, vaccine inoculation into scarified skin (the s.s. route) was the first immunization method. However, it does not allow accurate vaccine dosing, and high-dose vaccines need to be used to successfully complete this procedure. Intradermal (i.d.) vaccine injection, especially low-dose one, can be an alternative to the s.s. route. This study aimed to compare the s.s. and i.d. smallpox immunization routes in a mouse model when using prototypic second- and fourth-generation low-dose vaccines (104 pfu). Experiments were conducted using BALB/c mice; the LIVP or LIVP-GFP strains of the vaccinia virus (VACV) were administered into the tail skin via the s.s. or i.d. routes. After vaccination (7, 14, 21, 28, 42, and 56 days post inoculation (dpi)), blood samples were collected from the retro-orbital venous sinus; titers of VACV-specific IgM and IgG in the resulting sera were determined by ELISA. Both VACV strains caused more profound antibody production when injected via the i.d. route compared to s.s. inoculation. In order to assess the level of the elicited protective immunity, mice were intranasally infected with a highly lethal dose of the cowpox virus on 62 dpi. The results demonstrated that i.d. injection ensures a stronger protective immunity in mice compared to s.s. inoculation for both VACV variants.

The process of the labor collective formation of the Ulyanovsk Automobile Plant during the Great Patriotic War is studied. The relevance of the study is due to the need for a detailed study of the mechanisms of the automotive industry functioning in the extreme conditions of the Great Patriotic War. Documents on the history of the enterprise evacuation, materials of the primary party organization of the automobile plant, office work documentation of the party and state authorities, factory and departmental reports, and eye-witness accounts of the events were used as sources. The process of creating the Ulyanovsk Automobile Plant, constructed on the basis of the evacuated equipment and labor resources of the Moscow Automobile Plant named after I.V. Stalin (ZIS), is considered. Changes in the number and composition of the enterprise's employees during 1941—1945 are analyzed. Particular attention is paid to the interdependence of the change in the number of employees of the plant on the volume of industrial output. It is concluded that thanks to the evacuation of experienced engineers, production managers and highly skilled workers, it was possible to maintain and recreate hightech production in the rear areas of the country. It was noted that the enterprises created during the evacuation laid the foundation for the development of automotive production in the Volga region and the Urals.

At the present time, vast majority of human population lacks immunity against orthopoxvirus infections caused by variola (smallpox), monkeypox, cowpox, or buffalopox viruses. More and more mass outbreaks of orthopoxvirus infections are yearly registered among humans on different continents. To prevent transition of these outbreaks to widespread epidemics, we should develop appropriate immunoprophylaxis strategies. Currently, massive usage of the classic live vaccine based on vaccinia virus is not acceptable, due to its high reactogenicity. Therefore, it is necessary to develop the variants of vaccinia virus with reduced virulence and increased immunogenicity/protectivity. The aim of this work was to study protective effects against a lethal orthopoxvirus infection occuring after low-dose immunization of mice with vaccinia virus variants, i.e., carrying mutant A34R gene causing increased production of extracellular virions, or a A35R gene deletion encoding protein product inhibiting antigen presentation by the major histocompatibility complex class II. The LIVP viral strain used in Russia as a smallpox vaccine, and its recombinant variants (LIVP-A34R*, LIVP-dA35R and LIVP-A34R*-dA35R) were compared with intranasal or intradermal immunization of BALB/c mice at the doses of 105 or 103 PFU. 28 days following administration of viral preparations (experimental groups) or saline (control groups), the mice underwent intravital blood sampling from retroorbital venous sinus. The levels of virion-specific antibodies were determined in individual serum samples by enzyme immunoassay. On the day 30 of experiment, the mice were infected with cowpox virus at a dose of 32 LD50, which caused total death of control mice on days 6-10. In the groups immunized with the studied viruses at a dose of 105 PFU, all the animals survived, regardless of strain, or immunization method. Upon intradermal immunization (103 PFU) of mice immunized with the original LIVP virus, 83% of the animals survived, whereas all mutant strains of the vaccinia virus provided 100% protection of the mice from subsequent cowpox virus infection. Intranasal immunization of mice at a dose of 103 PFU with LIVP strain protected only 33% of animals from lethal infection with cowpox virus, while the mutant strains LIVP-A34R* and LIVP-A34R*-dA35R provided 67% protection, and the LIVP-dA35R strain has resqued 75% of the mice. The studied mutant vaccinia viruses can be considered not only new candidate vaccines against smallpox and other human orthopoxvirus infections, but also as vector platforms for creating live multivalent vaccines against other infectious diseases.

Smallpox eradication and lack of adequate animal model for smallpox infection underlies a necessity to assess immunogenic and protective properties of genetic engineering-created live attenuated smallpox vaccines in several animal models of orthopoxviral infections. Here we compared immunogenic and protective properties of the recombinant vaccinia virus (VACV) LIVP-GFP intradermally (i.d.) inoculated to mice, guinea pigs and rabbits. LIVP-GFP immunization in all animal species was applied at dose of 2 × 104 or 2 × 106 PFU. Control animals were injected with saline. Blood sampling was performed on day 28 after virus LIVP-GFP or saline inoculation. Blood samples were taken intravitally from the retro-orbital venous sinus in mice, heart in guinea pigs or marginal ear vein in rabbits. Serum samples were isolated by precipitating blood cells via centrifugation. The serum anti-VACV IgG titers were determined by ELISA. On day 30 post-immunization animals were intranasally challenged with lethal dose of host specific orthopoxvirus species. Mice were infected by cowpox virus (CPXV) strain GRI-90 at dose 68 LD50, guinea pigs – by VACV GPA at dose 56 LD50, rabbits — by VACV HB-92 at dose 100 LD50. All animals in control group died afterwards, whereas all animals immunized by attenuated recombinant virus LIVP-GFP at dose 2 × 106 PFU survived. In case of the LIVP-GFP immunization at dose 2 × 104 PFU, 88% of mice, 67% of rabbits and 50% of guinea pigs survived after being challenged with species-specific CPXV, VACV HB-92, and VACV GPA. ELISA data for the blood serum samples revealed a correlation between level of VACV-specific antibodies and level of protection in animal species. Based on the data obtained, it could be concluded that all three “animal–orthopoxvirus” models allow to provide with a proper evaluation of immunogenicity and protectiveness for generated modern attenuated vaccines against smallpox and other orthopoxviral human infections. Upon that, it was shown that BALB/c mouse strain was the most convenient investigational host species.

Vaccination is the most simple and reliable approach of protection to virus infections. The most effective agents are live vaccines, usually low-virulence organisms for humans and closely related to pathogenic viruses or attenuated as a result of mutations/deletions in the genome of pathogenic virus. Smallpox vaccination with live vaccinia virus (VACV) closely related to smallpox virus played a key role in the success of the global smallpox eradication program carried out under the World Health Organization auspices. As a result of the WHO decision as of 1980 to stop smallpox vaccination, humankind has lost immunity not only to smallpox, but also to other zoonotic, orthopoxviruscaused human infections. This new situation allows orthopoxviruses to circulate in the human population and, as a consequence, to alter several established concepts of the ecology and range of sensitive hosts for various orthopoxvirus species. Classic VACV-based live vaccine for vaccination against orthopoxvirus infections is out of the question, because it can cause severe side effects. Therefore, the development of new safe vaccines against orthopoxviral infections of humans and animals is an important problem. VACV attenuation by modern approaches carried out by targeted inactivation of certain virus genes and usually leads to a decrease in the effectiveness of VACV in vivo propagation. As a result, it can cause a diminishing of the immune response after administration of attenuated virus to patients at standard doses. The gene for thymidine kinase is frequently used for insertion/inactivation of foreign genes and it causes virus attenuation. In this research, the effect of the introduction of two point mutations into the A34R gene of attenuated strain LIVP-GFP (ТК–), which increase the yield of extracellular enveloped virions (EEV), on the pathogenicity and immunogenicity of VACV LIVP-GFP-A34R administered intranasally to laboratory mice were studied. It was shown that increase in EEV production by recombinant strain VACV LIVP-GFP-A34R does not change the attenuated phenotype characteristic of the parental strain LIVP-GFP, but causes a significantly larger production of VACV-specific antibodies.

Vaccinia virus had played a key role in the global smallpox eradication. However, in case of mass vaccination with various Vaccinia virus strains severe side effects were revealed sometimes ending up with lethal outcomes, especially in immunocompromised humans. Hence, in 1980 the World Health Organization recommended to cancel smallpox vaccination after declaring about smallpox eradication. Over the last 40 years, human population virtually lost immunity not only against smallpox, but also against other zoonotic orthopoxvirus infections, such as monkeypox, cowpox, buffalopox, and camelpox. All of them pose a represent increasing threat to human health and heighten a risk of emerging highly contagious viruses due to natural evolution of previous zoonotic orthopoxviruses. In order to prevent development of small outbreaks into spreading epidemics and, thus, to decrease a risk of emergence due to natural evolution of highly pathogenic for humans orthopoxviruses, efforts should be applied to develop safe new generation live vaccines based on Vaccinia virus with target virulence genes inactivation. These strains should be examined in laboratory animal models inoculated via different routes. Currently, Vaccinia virus often becomes attenuated to create live recombinant vaccines due to inserting target DNA sequences into the virus virulence genes resulting in their inactivation. Vaccinia virus strain LIVP used in the Russian Federation as smallpox vaccine as well as derivative attenuated variant LIVP-GFP created by using genetic engineering methods with inactivating its thymidine kinase gene were examined. Such viruses were intracerebrally inoculated into suckling mice at doses of 101 or 102 PFU/animal for neurovirulence assessment. Adult mice were infected intranasally, subcutaneously or intradermally at doses of 107 or 108 PFU/animal and clinical manifestations were analyzed for 14 days. On the 28th day after the onset, blood serum samples were collected from individual mice to measure virus specific antibody level by using ELISA. It was shown that recombinant Vaccinia virus strain LIVP-GFP displayed markedly lowered neurovirulence and pathogenicity for mice as compared to parental LIVP. Finally, intradermal route turned out to demonstrate the most safe and effective profile for immunization with both examined Vaccinia virus strains.

Vaccination of the population is one of the most effective countermeasures in responding to the pandemic caused by novel coronavirus infection. Therefore, scientists all over the world have been working to develop effective and safe vaccines. We have developed a synthetic peptide vaccine, EpiVacCorona, against novel SARS-CoV-2 coronavirus, which is a suspension for intramuscular administration containing a composition of chemically synthesized peptide immunogens of the S protein of SARS-CoV-2 coronavirus conjugated to a carrier protein and adsorbed on aluminum hydroxide. Phase I–II clinical trials of the vaccine have started that consist of two stages: Stage 1 is an open study of the safety, reactogenicity, and immunological activity of the vaccine with the involvement of 14 volunteers aged 18–30 years; Stage 2 is a single blind, comparative, randomized placebo-controlled study with the involvement of 86 volunteers. The study involved volunteers aged 18–60 years; the vaccine was injected intramuscularly twice, spaced 21 days apart between injections. All local reactions in response to vaccine administration were mild, such as a short-term pain at the injection site. There were no signs of development of local or systemic adverse reactions. The two-dose vaccination scheme induced the production of antibodies, specific to the antigens that make up the vaccine, in 100% of the volunteers. Seroconversion with a neutralizing antibody titer ≥ 1:20 was reported in 100% of the volunteers 21 days following the second immunization dose. No seroconversion was reported in the groups of volunteers vaccinated with a placebo. The peptide-based EpiVacCorona Vaccine has low reactogenicity and is a safe, immunogenic product. Clinical Trials Identifier: NCT04527575.

The causative agent of Zika fever (ZIKV) belongs to the genus Flavivirus of the family Flaviviridae. The flavivirus genus consists of more than 70 members. Based on virion structural organization and amino acid composition of proteins, this virus resembles other flaviviruses such as dengue (DENV), yellow fever and West Nile (WNV) posing a threat to human health. ZIKV is an arbovirus and may be transmitted by diverse mosquito species of the genus Aedes. It is believed that the main carriers are also able to transmit dengue virus, yellow fever virus as well as other flavivirus infections. In 1947, ZIKV was isolated for the first time from blood samples obtained from rhesus macaques inhabiting the Zika Forest (Uganda). Long time this virus was not considered as a dangerous to human pathogen, as Zika fever mostly occurs asymptomatically. However, analysis of Zika fever course in pregnant women unveiled a link between this disease and severe congenital disorders of the nervous system, including microcephaly, that allowed to deal with it as a dangerous infection thereafter. Rapid ZIKV spread outlined a number of problems faced by medical doctors, among which the main issue was the lack of assays for its virus-specific diagnostics. ZIKV displays a marked antigenic similarity with other flaviviruses. The majority of dengue-specific monoclonal antibodies binds to Zika virus. It is expected given the high degree of amino acid sequence similarity found for flavivirus polyprotein. Several antigens bearing ZIKV E surface protein fragments were constructed to assess an opportunity for conducting differential diagnostics for distinct flaviviruses based on detection of virus-specific antibodies. Vector plasmid pET32 was selected for producing recombinant antigens in E. coli cells. After creating constructs encoding the ZEa187 and ZEa40 proteins, the chimeric proteins were produced in amount necessary for performing ELISA with blood serum samples. Protein samples were prepared by isolating them from bacterial biomass via lysis followed by chromatographic purification. Blood sera obtained from human subjects recovered after Zika, Dengue and West Nile fevers were used to examined immunochemical properties of chimeric proteins. Human sera containing no antibodies against flavivirus types were used as a negative control. It was found that serum IgM class antibodies derived from patients with flavivirus infections demonstrated a high level of cross-reactivity by interacting with ZEa187 and ZEa40. Upon that, despite increment of mean specific interaction signal observed for such proteins and IgG of ZIKV sera, a marked cross-reactivity with the IgG of WNV and DENV sera was found. Thus, with some certainty it may be concluded that in immunochemical assays use of natural amino acid sequence specific to Zika virus surface protein as antigenic material does not allow to achieve high specificity for antibody detection.

Ebola virus disease is dangerous viral infection, occurring in the form of hemorrhagic fever, characterized by acute clinical symptoms and high mortality rate due to multiple organ failure. Ebola virus natural foci are located in forested areas of the central and western parts of Africa. It was believed for many years, the incidence of Ebola virus disease has been sporadic and the burden of it is true only in endemic areas. However, the unprecedented Ebola epidemic caused by Zaire virus in 2013 — 2016, has significantly changed our understanding of this disease and the patterns of its distribution. We have also identified weaknesses in the organization of anti-epidemic measures, the effectiveness of which was not very effective at the onset of the epidemic, in particular due to weak development of in vitro diagnostics (IVD). However, during the elimination of the epidemic in West Africa, anti-epidemic system has been modified substantially, largely due to quickly developed IVD kits. This review is devoted to analysis of trends in IVD for Ebola virus disease based on the experience obtained in the course of the West-African epidemic in 2013 — 2016.

The possibility to use the global numerical (NWP) models ICON and GFS/NCEP for We consider the applicability of ICON and GFS/NCEP global numerical atmospheric model data for calculating the snow water equivalent (SWE) in the Selenga River basin located the semiarid zone. SWE was calculated for the cold periods of 2020–2022 based on the empirical methodology previously developed for the Kama River basin and adapted to the semiarid conditions. The main components of the SWE balance that are taken into account in the calculation are atmospheric precipitation (liquid or solid phase), snowmelt, sublimation from the snow surface and precipitation interception by vegetation with subsequent sublimation. The validation of the results was performed for the Russian part of the basin using the data of snow surveys carried out in the second half of the winter of 2021/22. In general, reasonable estimates of the SWE spatial distribution were obtained. While in 2021, both overestimation and underestimation by 1–15 mm (20–50%) of the calculated SWE was observed at different sites compared to the measurements, in 2022, its systematic underestimation was observed, especially significant in calculations using the ICON model data. In the steppe zone, SWE is significantly underestimated, which may be due to overestimation of the intensity of sublimation from the snow surface. The comparison of these results with the ERA5-Land reanalysis data and MODIS satellite images showed that the ERA5-Land reanalysis significantly overestimates the SWE and the snow cover area. The simulation results based on the GFS/NCEP and ICON models underestimated the snow cover area in 2022 and reproduced well in 2021, which correlates with the results of the SWE calculation.

The paper highlights the features of the creation of the basin GIS, developed to support the environmental monitoring, assessment and forecasting of negative consequences in the areas of technogenic disaster (on the example of abandoned Kizel coal basin, located in Perm Region, Russia). The world experience of applying GIS-technologies for solving environmental problems of coal-mining regions is also being discussed. The information basis and structure of the cartographic and attributive database of the Kizel coal basin GIS are presented. The main tasks of creating the GIS, including inventory of man-made impact sources, identification of the spatio-temporal distribution patterns of pollutants, quantification and mapping of the territory ecological status, forecasting of the environmental situation and planning of environmental measures have been identified. A system of spatial criteria for the integrated assessment of the territory ecological status within coal basins is proposed, which will allow monitoring of environmental changes and identifying areas with the critical environmental situation. These criteria include the pH value and the sulfates concentration in the streams, the complex of heavy metals, the species composition of microorganisms in surface waters, the area of degraded land and dead forest stands. The degree of negative impact of the abandoned coal mines on streams and groundwater is described, and the priority pollutants are identified.The estimates of the extent of contaminated streams, as well as areas of potential contamination of floodplain lands have been obtained using LANDSAT satellite imagery data. The significance of the creation of the algorithms for the integration of heterogeneous spatial information (ground-based and remote sensing observations) for compiling synthetic maps that objectively estimate the ecological situation has been noted.

This article analyzes the application of remote sensing data for operational monitoring of hydrometeorological hazards, and estimation of their consequences on the territory of Perm region. The author shows the necessity of application of remote sensing data on the example of three problems in the study area. There are problems of monitoring of hydrological hazards in the period of spring high water, monitoring of the development of droughts and estimation of damage from hydrometeorological hazards for forest resources of the region.