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The basis for criteria of the taxonomic classification of DNA and RNA viruses based on data of the genomic sequencing are viewed in this review. The genomic sequences of viruses, which have genome represented by double-stranded DNA (orthopoxviruses as example), positive-sense single-stranded RNA (alphaviruses and flaviviruses as example), non-segmented negative-sense single-stranded RNA (filoviruses as example), segmented negative-sense single-stranded RNA (arenaviruses and phleboviruses as example) are analyzed. The levels of genetic variability that determine the assignment of compared viruses to taxa of various orders are established for each group of viruses.

Introduction: When a new disease occurs, one of the most affordable remedies is drugs containing specific antibodies to this infectious agent. The use of such drugs is aimed at reducing the amount of the pathogen in the macroorganism and the associated reduction in the severity of the symptoms of the disease or recovery. The purpose of this review is to analyze the experience of using immunoglobulins and monoclonal antibodies in the treatment of COVID-19 patients during the pandemic., Results and Conclusion: The two main groups of medical protective agents that block the penetration of the SARS-CoV-2 virus into permissive cells are drugs obtained from blood plasma of convalescents (immunoglobulin) and human monoclonal antibodies. The first group of drugs in the treatment of COVID-19 includes blood plasma of convalescents, which can be successfully used for emergency prevention. The main disadvantage of using blood plasma convalescents is the difficulty of standardization due to the different content of specific antibodies in donors. Another disadvantage is the undesirable side effects in recipients that occur after plasma administration. An alternative approach to COVID-19 therapy is the use of humanized and genetically engineered human monoclonal antibodies against certain epitopes of the SARS-CoV-2 virus. For example, monoclonal antibodies against receptor-binding domain of the S-protein, which prevents the virus from entering permissive cells and interrupts the development of infection. The advantages of these drugs are their safety, high specific activity, and the possibility of standardization. However, the complexity of their production and high cost make them inaccessible for mass use in practical medicine.

Relevance: Ebola virus disease (EVD) is an acute infectious disease with an extremely high case fatality rate reaching up to 90%. EVD has become widely known since 2014-2016, when outbreak in West Africa occurred and led to epidemic, which caused travel-related cases on the territory of other continents. There are two vaccines against EVD, prequalified by WHO for emergency use, as well as a number of vaccines, approved by local regulators in certain countries. However, even with the availability of effective vaccines, the lack of data on immune correlates of protection and duration of protective immune response in humans and primates is limiting factor for effectively preventing the spread of EVD outbreaks., Aims: This review highlights experience of use of EVD vaccines during outbreaks in endemic areas, summarizes data on vaccine immunogenicity in clinical trials, and discusses perspectives for further development and use of effective EVD vaccines.

WHO has declared the outbreak of monkeypox as a public health emergency of international concern. In less than three months, monkeypox was detected in more than 30 000 people and spread to more than 80 countries around the world. It is believed that the immunity formed to smallpox vaccine can protect from monkeypox infection with high efficiency. The widespread use of Vaccinia virus has not been carried out since the 1980s, which raises the question of the level of residual immunity among the population and the identification of groups requiring priority vaccination. We conducted a cross-sectional serological study of remaining immunity among Moscow residents. To do this, a collection of blood serum samples of age group over 30 years old was formed, an in-house ELISA test system was developed, and a virus neutralization protocol was set up. Serum samples were examined for the presence of IgG antibodies against Vaccinia virus ( n =2908), as well as for the ability to neutralize plaque formation with a Vaccinia virus MNIIVP-10 strain ( n =299). The results indicate the presence of neutralizing antibody titer of 1/20 or more in 33.3 to 53.2% of people older than 45 years. Among people 30-45 years old who probably have not been vaccinated, the proportion with virus neutralizing antibodies ranged from 3.2 to 6.7%. Despite the higher level of antibodies in age group older than 66 years, the proportion of positive samples in this group was slightly lower than in people aged 46-65 years. The results indicate the priority of vaccination in groups younger than 45, and possibly older than 66 years to ensure the protection of the population in case of spread of monkeypox among Moscow residents. The herd immunity level needed to stop the circulation of the virus should be at least 50.25 - 65.28%., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Gushchin, Ogarkova, Dolzhikova, Zubkova, Grigoriev, Pochtovyi, Iliukhina, Ozharovskaia, Kuznetsova, Kustova, Shelkov, Zrelkin, Odintsova, Grousova, Kan, Davtyan, Siniavin, Belyaeva, Botikov, Bessonova, Vasilchenko, Vasina, Kleymenov, Slutskiy, Tkachuk, Burgasova, Loginova, Rozhdestvensky, Shcheblyakov, Tsibin, Komarov, Zlobin, Borisevich, Naroditsky, Logunov and Gintsburg.)

Objective and Design: The existing biological models of diffuse alveolar damage (DAD) in mice have many shortcomings. To offset these shortcomings, we have proposed a simple, nonsurgical, and reproducible method of unilateral total damage of the left lung in ICR mice. This model is based on the intrabronchial administration of a mixture of bacterial lipopolysaccharide (LPS) from the cell wall of S. enterica and α-galactosylceramide (inducing substances) to the left lung., Methods: Using computer tomography of the lungs with endobronchial administration of contrast material, we have been able to perform an operative intravital verification of the targeted delivery of the inducer. The model presented is characterized by more serious and homogeneous damage of the affected lung compared to the existing models of focal pneumonia; at the same time, our model is characterized by longer animal survival since the right lung remains intact., Results: The model is also characterized by diffuse alveolar damage of the left lung, animal survival of 100%, abrupt increases in plasma levels of TNFa, INFg, and IL-6, and significant myocardial overload in the right heart. It can be used to assess the efficacy of innovative drugs for the treatment of DAD and ARDS as the clinical manifestations that are developed in patients infected with SARS-CoV-2. Morphological patterns of lungs in the noninfectious ("sterile") model of DAD induced by LPS simultaneously with α-galactosylceramide (presented here) and in the infectious model of DAD induced by SARS-CoV-2 have been compared., Conclusion: The DAD model we have proposed can be widely used for studying the efficacy of candidate molecules for the treatment of infectious respiratory diseases, such as viral pneumonias of different etiology, including SARS-CoV-2., (© 2022. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

Since the Dabie bandavirus (DBV; former SFTS virus, SFTSV) was identified, the epidemics of severe fever with thrombocytopenic syndrome (SFTS) caused by this virus have occurred in several countries in East Asia. The rapid increase in incidence indicates that this infectious agent has a pandemic potential and poses an imminent global public health threat.The analysis of molecular evolution of SFTS agent that includes its variants isolated in China, Japan and South Korea was performed in this review. The evolution rate of DBV and the estimated dates of existence of the common ancestor were ascertained, and the possibility of reassortation was demonstrated.The evolutionary rates of DBV genome segments were estimated to be 2.28 × 10-4 nucleotides/site/year for S-segment, 2.42 × 10-4 for M-segment, and 1.19 × 10-4 for L-segment. The positions of positive selection were detected in the viral genome.Phylogenetic analyses showed that virus may be divided into two clades, containing six different genotypes. The structures of phylogenetic trees for S-, M- and L-segments showed that all genotypes originate from the common ancestor.Data of sequence analysis suggest that DBV use several mechanisms to maintain the high level of its genetic diversity. Understanding the phylogenetic factors that determine the virus transmission is important for assessing the epidemiological characteristics of the disease and predicting its possible outbreaks.

Over the two years that have passed since the WHO announced on March 11, 2020, a pandemic of the new coronavirus disease COVID-19, more than 460 million cases of the disease have been detected in the world, of which more than five million have been fatal. During the natural evolution of the COVID-19 pathogen, dominant variants emerge that account for most new infections. The WHO constantly monitors coronavirus mutations that potentially pose an epidemiological danger. Currently, the WHO divides modified variants of the SARS-CoV-2 virus into variants of concern (VOC) and variants of interest (VOI). The WHO-designated group of variants of concern includes potentially the most dangerous lines, which are characterized by a complex of new properties. This group also includes the Omicron variant, which has become the dominant agent of the new wave of the COVID-19 pandemic. The aim of this work is to analyze the characteristics of the SARS-CoV-2 Omicron strain, the dominant agent of the new wave of the COVID-19 pandemic. The proposed mechanism of origin of the Omicron variant, its geographical distribution, the features of the disease caused by it, and the distinguishing features from diseases caused by the Delta variant and the original Wuhan strain of the SARS-CoV-2 virus, mutations of the Omicron variant compared to the parent strain of the SARS-CoV-2 virus, the genetic variability of the Omicron variant, and the epidemiological characteristics of the disease it causes are considered. Particular attention is paid to evaluation of the preventive and therapeutic effectiveness of the existing medical means of protection against COVID-19 in relation to the Omicron strain., Competing Interests: The authors declare that they have no conflicts of interest., (© Pleiades Publishing, Ltd. 2022, ISSN 1019-3316, Herald of the Russian Academy of Sciences, 2022, Vol. 92, No. 4, pp. 381–391. © Pleiades Publishing, Ltd., 2022.Russian Text © The Author(s), 2022, published in Vestnik Rossiiskoi Akademii Nauk, 2022, Vol. 92, No. 7, pp. 636–646.)

Background: While the world is experiencing another wave of COVID-19 pandemic, global vaccination program is hampered by an evident shortage in the supply of licensed vaccines. In an effort to satisfy vaccine demands we developed a new single-dose vaccine based on recombinant adenovirus type 26 (rAd26) vector carrying the gene for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike (S) glycoprotein - "Sputnik Light"., Methods: We conducted an open label, prospective, non-randomised phase 1/2 trial aimed to assess safety, tolerability, and immunogenicity of "Sputnik Light" vaccine in a single center in Russia. Primary outcome measures were antigen-specific humoral immunity (Anti-RBD-SARS-CoV-2 antibodies measured by ELISA on days 1, 10, 28, and 42) and safety (number of participants with adverse events monitored throughout the study). Secondary outcome measures were antigen-specific cellular immunity (measured by antigen-dependent CD4+ and CD8+ T-cell proliferation, number of antigen-specific interferon-γ-producing cells as well as interferon-γ concentration upon antigen restimulation) and change in neutralizing antibodies (measured in SARS-CoV-2 neutralization assay)., Findings: Most of the solicited adverse reactions were mild (66 · 4% from all vaccinees), few were moderate (5·5%). No serious adverse events were detected. Assessment of Anti-RBD-SARS-CoV-2 antibodies revealed a group with pre-existing immunity to SARS-CoV-2. Upon this finding we separated all safety and immunogenicity data based on pre-existing immunity to SARS-CoV-2. There were notable differences in the vaccine effects on immunogenicity by the groups. Vaccination of seropositive (N=14) volunteers rapidly boosted RBD-specific IgGs from reciprocal geometric mean titer (​GMT) 594·4 at a baseline up to 26899 comparing to 29·09 in seronegative group (N=96) by day 10. By day 42 seroconversion rate reached 100% (93/93) in seronegative group with GMT 1648. At the same time, in the seropositive group, seroconversion rate by day 42 was 92·9% (13/14) with GMT 19986. Analysis of neutralizing antibodies to SARS-CoV-2 showed 81·7% (76/93) and 92·9% (13/14) seroconversion rates by day 42 with median reciprocal GMT 15·18 and 579·7 in the seronegative and seropositive groups, respectively. Antigen-specific T cell proliferation, formation of IFNy-producing cells, and IFNy secretion were observed in 96·7% (26/27), 96% (24/25), and 96% (24/25) of the seronegative group respectively and in 100% (3/3), 100% (5/5), and 100% (5/5) of the seropositive vaccinees, respectively., Interpretation: The single-dose rAd26 vector-based COVID-19 vaccine "Sputnik Light" has a good safety profile and induces a strong humoral and cellular immune responses both in seronegative and seropositive participants., Funding: Russian Direct Investment Fund., Competing Interests: OVZ, TAO, IVD, OP, DVS, DMG, ASD, AIT, DNS, IBE, EAT, AGB, ASE, FMI, NAN, NLL, ASS, SVB, BSN, DYL, ALG report patents for an immunobiological expression vector, pharmaceutical agent, and its method of use to prevent COVID-19. All other authors declare no competing interests., (© 2021 The Author(s).)

Ebola fever is an acute, highly contagious viral disease with a mortality rate that can reach 90%. There are currently no licensed therapeutic agents specific to Ebola in the world. Monoclonal antibodies (MAbs) with viral-neutralizing activity and high specificity to the Ebola virus glycoprotein (EBOV GP) are considered as highly effective potential antiviral drugs. Over the past decade, nanobodies (single-domain antibodies, non-canonical camelid antibodies) have found wide use in the diagnosis and treatment of various infectious and non-infectious diseases. In this study, a panel of nanobodies specifically binding to EBOV GP was obtained using recombinant human adenovirus 5, expressing GP (Ad5-GP) for alpaca (Vicugna pacos) immunization, for the first time. Based on specific activity assay results, affinity constants, and the virus-neutralizing activity against the recombinant vesicular stomatitis virus pseudotyped with EBOV GP (rVSV-GP), the most promising clone (aEv6) was selected. The aEv6 clone was then modified with the human IgG1 Fc fragment to improve its pharmacokinetic and immunologic properties. To assess the protective activity of the chimeric molecule aEv6-Fc, a lethal model of murine rVSV-GP infection was developed by using immunosuppression. The results obtained in lethal model mice have demonstrated the protective effect of aEv6-Fc. Thus, the nanobody and its modified derivative obtained in this study have shown potential protective value against Ebola virus., (Copyright ® 2021 National Research University Higher School of Economics.)

Introduction: The outbreaks of the Zaire ebolavirus (ZE) disease (ZED) that have arisen in the last decade determine the need to study the infection pathogenesis, the formation of specific immunity forming as well as the development of effective preventive and therapeutic means. All stages of fight against the ZED spread require the experimental infection in sensitive laboratory animals, which are rhesus monkeys in case of this disease .The aim of the study is to evaluate the rhesus monkey cellular immunity following the ZE experimental infection by the means of flow cytometry (cytofluorimetry)., Material and Methods: Male rhesus monkeys were intramuscularly infected by the dose of 15 LD50 (dose of the pathogen that causes 50% mortality of infected animals) of the ZE, the Zaire strain (ZEBOV). Levels of 18 peripheral blood lymphocyte populations of the animals before the ZE experimental infection and at the terminal stage of the disease were assessed using flow cytometry., Results and Discussion: The certain changes in the levels of the lymphocyte populations were observed following infection, indicating simultaneous activation and suppression of the immune system during ZED. The increase in content was observed for T-lymphocytes, T-helper and cytotoxic T-lymphocytes expressing the corresponding markers of early activation. The decrease was recorded for T-lymphocytes and double-positive T-lymphocytes expressing corresponding markers of late activation, as well as natural killer cells expressing CD8 (p < 0.05)., Conclusion: For the first time in the Russian Federation, the rhesus monkey cellular immunity before and after the ZE experimental infection was assessed using flow cytometry.

Introduction: The pandemic spread of a new coronavirus infection, COVID-19, has caused a global emergency and attracted the attention of public health professionals and the population of all countries. A significant increase in the number of new cases of SARS-CoV-2 infection demonstrates the urgency of finding drugs effective against this pathogen.The aim of this work was to evaluate the in vitro antiviral efficacy of human recombinant alpha-2b interferon (IFN-α2b) against SARS-CoV-2 virus., Material and Methods: The experiments had been carried out on Vero Cl008, the continuous line of African green monkey (Chlorocebus sabaeus) kidney cells. The effectiveness of the drugs was assessed by the suppression of viral reproduction in vitro. The biological activity was determined using titration of a virus-containing suspension in a Vero Cl008 cell culture by the formation of negative colonies., Results: The antiviral efficacy of the IFN-α2b-based medications, which have a high safety profile and proven efficacy in the prevention and treatment of influenza and acute respiratory viral infections (ARVI), has been studied against the new pandemic SARS-CoV-2 virus in vitro experiments in Vero C1008 cell culture. IFN-α2b effectively inhibits the reproduction of the virus when applied both 24 hrs before and 2 hrs after infection. In the IFN-α2b concentration range 102-106 IU/ml a complete suppression of the reproduction of the SARS-CoV-2 virus had been demonstrated., Discussion: IFN-α2b demonstrated in vitro high antiviral activity against SARS-CoV-2. In addition, the substance has a high chemotherapeutic index (>1000)., Conclusion: Medications for intranasal use based on IFN-α2b have high antiviral activity and are promising drugs for in vivo study in terms of prevention and treatment of COVID-19.

Background: A heterologous recombinant adenovirus (rAd)-based vaccine, Gam-COVID-Vac (Sputnik V), showed a good safety profile and induced strong humoral and cellular immune responses in participants in phase 1/2 clinical trials. Here, we report preliminary results on the efficacy and safety of Gam-COVID-Vac from the interim analysis of this phase 3 trial., Methods: We did a randomised, double-blind, placebo-controlled, phase 3 trial at 25 hospitals and polyclinics in Moscow, Russia. We included participants aged at least 18 years, with negative SARS-CoV-2 PCR and IgG and IgM tests, no infectious diseases in the 14 days before enrolment, and no other vaccinations in the 30 days before enrolment. Participants were randomly assigned (3:1) to receive vaccine or placebo, with stratification by age group. Investigators, participants, and all study staff were masked to group assignment. The vaccine was administered (0·5 mL/dose) intramuscularly in a prime-boost regimen: a 21-day interval between the first dose (rAd26) and the second dose (rAd5), both vectors carrying the gene for the full-length SARS-CoV-2 glycoprotein S. The primary outcome was the proportion of participants with PCR-confirmed COVID-19 from day 21 after receiving the first dose. All analyses excluded participants with protocol violations: the primary outcome was assessed in participants who had received two doses of vaccine or placebo, serious adverse events were assessed in all participants who had received at least one dose at the time of database lock, and rare adverse events were assessed in all participants who had received two doses and for whom all available data were verified in the case report form at the time of database lock. The trial is registered at ClinicalTrials.gov (NCT04530396)., Findings: Between Sept 7 and Nov 24, 2020, 21 977 adults were randomly assigned to the vaccine group (n=16 501) or the placebo group (n=5476). 19 866 received two doses of vaccine or placebo and were included in the primary outcome analysis. From 21 days after the first dose of vaccine (the day of dose 2), 16 (0·1%) of 14 964 participants in the vaccine group and 62 (1·3%) of 4902 in the placebo group were confirmed to have COVID-19; vaccine efficacy was 91·6% (95% CI 85·6-95·2). Most reported adverse events were grade 1 (7485 [94·0%] of 7966 total events). 45 (0·3%) of 16 427 participants in the vaccine group and 23 (0·4%) of 5435 participants in the placebo group had serious adverse events; none were considered associated with vaccination, with confirmation from the independent data monitoring committee. Four deaths were reported during the study (three [<0·1%] of 16 427 participants in the vaccine group and one [<0·1%] of 5435 participants in the placebo group), none of which were considered related to the vaccine., Interpretation: This interim analysis of the phase 3 trial of Gam-COVID-Vac showed 91·6% efficacy against COVID-19 and was well tolerated in a large cohort., Funding: Moscow City Health Department, Russian Direct Investment Fund, and Sberbank., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Background: We developed a heterologous COVID-19 vaccine consisting of two components, a recombinant adenovirus type 26 (rAd26) vector and a recombinant adenovirus type 5 (rAd5) vector, both carrying the gene for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike glycoprotein (rAd26-S and rAd5-S). We aimed to assess the safety and immunogenicity of two formulations (frozen and lyophilised) of this vaccine., Methods: We did two open, non-randomised phase 1/2 studies at two hospitals in Russia. We enrolled healthy adult volunteers (men and women) aged 18-60 years to both studies. In phase 1 of each study, we administered intramuscularly on day 0 either one dose of rAd26-S or one dose of rAd5-S and assessed the safety of the two components for 28 days. In phase 2 of the study, which began no earlier than 5 days after phase 1 vaccination, we administered intramuscularly a prime-boost vaccination, with rAd26-S given on day 0 and rAd5-S on day 21. Primary outcome measures were antigen-specific humoral immunity (SARS-CoV-2-specific antibodies measured by ELISA on days 0, 14, 21, 28, and 42) and safety (number of participants with adverse events monitored throughout the study). Secondary outcome measures were antigen-specific cellular immunity (T-cell responses and interferon-γ concentration) and change in neutralising antibodies (detected with a SARS-CoV-2 neutralisation assay). These trials are registered with ClinicalTrials.gov, NCT04436471 and NCT04437875., Findings: Between June 18 and Aug 3, 2020, we enrolled 76 participants to the two studies (38 in each study). In each study, nine volunteers received rAd26-S in phase 1, nine received rAd5-S in phase 1, and 20 received rAd26-S and rAd5-S in phase 2. Both vaccine formulations were safe and well tolerated. The most common adverse events were pain at injection site (44 [58%]), hyperthermia (38 [50%]), headache (32 [42%]), asthenia (21 [28%]), and muscle and joint pain (18 [24%]). Most adverse events were mild and no serious adverse events were detected. All participants produced antibodies to SARS-CoV-2 glycoprotein. At day 42, receptor binding domain-specific IgG titres were 14 703 with the frozen formulation and 11 143 with the lyophilised formulation, and neutralising antibodies were 49·25 with the frozen formulation and 45·95 with the lyophilised formulation, with a seroconversion rate of 100%. Cell-mediated responses were detected in all participants at day 28, with median cell proliferation of 2·5% CD4 + and 1·3% CD8 + with the frozen formulation, and a median cell proliferation of 1·3% CD4 + and 1·1% CD8 + with the lyophilised formulation., Interpretation: The heterologous rAd26 and rAd5 vector-based COVID-19 vaccine has a good safety profile and induced strong humoral and cellular immune responses in participants. Further investigation is needed of the effectiveness of this vaccine for prevention of COVID-19., Funding: Ministry of Health of the Russian Federation., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

The Middle East Respiratory Syndrome (MERS) is an acute inflammatory disease of the respiratory system caused by the MERS-CoV coronavirus. The mortality rate for MERS is about 34.5%. Due to its high mortality rate, the lack of therapeutic and prophylactic agents, and the continuing threat of the spread of MERS beyond its current confines, developing a vaccine is a pressing task, because vaccination would help limit the spread of MERS and reduce its death toll. We have developed a combined vector vaccine for the prevention of MERS based on recombinant human adenovirus serotypes 26 and 5. Studies of its immunogenicity have shown that vaccination of animals (mice and primates) induces a robust humoral immune response that lasts for at least six months. Studies of the cellular immune response in mice after vaccination showed the emergence of a specific CD4 + and CD8 + T cell response. A study of the vaccine protectivity conducted in a model of transgenic mice carrying the human DPP4 receptor gene showed that our vaccination protected 100% of the animals from the lethal infection caused by the MERS-CoV virus (MERS-CoV EMC/2012, 100LD 50 per mouse). Studies of the safety and tolerability of the developed vaccine in rodents, rabbits, and primates showed a good safety profile and tolerance in animals; they revealed no contraindications for clinical testing., (Copyright ® 2020 National Research University Higher School of Economics.)

The Ebola virus (member of Ebolavirus genus Filoviridae family) is the etiologic agent of extremely hazard human disease with high mortality rates (up to 90%). The most important components of spectrum of therapeutics for special prophylactic and current of disease, caused by Ebola virus, are prepares, based on virus specific antibodies (convalescent's plasma, geterologic immunoglobulins, monoclonal antibodies. The use of different class therapeutics, based on virus specific antibodies, the possible improvements of its composition and strategy of its application for special prophylactic and current of disease, caused by Ebola virus, are considered in this review.

The Middle East respiratory syndrome coronavirus (MERS-CoV) was identified in 2012 during the first Middle East respiratory syndrome (MERS) outbreaks. MERS-CoV causes an acute lower-respiratory infection in humans, with a fatality rate of ~35.5%. Currently, there are no registered vaccines or means of therapeutic protection against MERS in the world. The MERS-CoV S glycoprotein plays the most important role in the viral life cycle (virus internalization). The S protein is an immunodominant antigen and the main target for neutralizing antibodies. In the present study, the immunogenicities of five different forms of the MERS-CoV S glycoprotein were compared: the full-length S glycoprotein, the full-length S glycoprotein with the transmembrane domain of the G glycoprotein of VSV (S-G), the receptor-binding domain (RBD) of the S glycoprotein, the membrane-fused RBD (the RBD fused with the transmembrane domain of the VSV G glycoprotein (RBD-G)), and the RBD fused with Fc of human IgG1 (RBD-Fc). Recombinant vectors based on human adenoviruses type 5 (rAd5) were used as delivery vehicles. Vaccination with all of the developed rAd5 vectors elicited a balanced Th1/Th2 response in mice. The most robust humoral immune response was induced after the animal had been vaccinated with the membrane-fused RBD (rAd5-RBD-G). Only immunization with membrane forms of the glycoprotein (rAd5-S, rAd5-S-G, and rAd5-RBD-G) elicited neutralizing antibodies among all vaccinated animals. The most significant cellular immune response was induced after vaccination of the animals with the full-length S (rAd5-S). These investigations suggest that the full-length S and the membrane form of the RBD (RBD-G) are the most promising vaccine candidates among all the studied forms of S glycoprotein.

The mosquitoes of Aedes genus are the most important vector such arboviral diseases as dengue, yellow, Chikungunya, West Nile and Zika fevers. Work is currently in progress to control the transmission of agents of these diseases by forming of transgenic mosquitoes in order to altering the capacity of wild mosquitoes to support of virus replication. There are two main strategies of genetic control of mosquitoes population. Sterile Insect Technique (SIT), that mainly uses population suppression methods for making self-sustaining genetic systems and Release of insects carrying of a Dominant Lethal (RIDL) that uses mainly gene transfer methods for making of self-limiting genetic systems. The RIDL is more expensive, but it has some significant preferences, according compares with SIT. The field trials of genetic control methods are conducted in several countries from 2009 to present time. Genetic control, transgenic technologies to induce sterility, genetic elimination and stable transformation of Aedes mosquitoes are viewed in this review., Competing Interests: The authors declare no conflict of interest.

Highly pathogenic avian influenza viruses (HPAIV) A(H5N8) of group B (Gochang1-like) have emerged in the Tyva Republic of eastern Russia in May 2016. Since November 2016, HPAIV A(H5N8) has spread throughout the European part of Russia. Thirty-one outbreaks were reported in domestic, wild and zoo birds in 2017. The present study aimed to perform a comparative analysis of new HPAIV A(H5N8) strains. Phylogenetic analysis revealed four genetically distinct subgroups in HPAIV A(H5N8) from the 2016-2017 season. Russian strains consisted of three subgroups with differences between isolates from Tyva, Siberia (Chany Lake), and the European part of Russia. Strains from the European part of Russia showed the beginnings of divergent evolution. Slight differences of the Voronezh strains were suggested by sensitivity to antiviral compounds. Testing for host-specific mutations in sequenced strains revealed the absence of mutations associated with possible increased tropism/virulence in mammalian species, including humans. Only one residue of polymerase basic-1, 13P, is discussed, because the L13P mutation increased complementary RNA synthesis in mammalian cells. We concluded that the evolution of HPAIV A(H5N8) is continuous. Surveillance in Russia revealed new cases of HPAIV A(H5N8) and led to the elaboration of prevention strategies, which should be implemented., (Copyright © 2018 Elsevier B.V. All rights reserved.)

The data on a recently revealed novel filovirus (Lloviu virus, family Filoviridae, genera Cuevavirus) in Europe are viewed in this issue. The molecular-biological properties of genome fragments of Lloviu virus were isolated from perished bats (Miniopterus sсhreibersii). Because infectious Lloviu virus has not been isolated yet, the capacity of virus to infect cells of different species and its potential to cause disease in humans is unclear. The recombinant vectors (vesicular stomatitis virus and plasmids) expressing structural proteins of Lloviu virus were used to study different elements of the virus. The question of interaction of structural proteins of Lloviu virus expressed by recombinant vectors with receptors of bat and human cells is considered. The possibility of pathogenicity of the novel agent for humans is considered. The conclusion is made about the necessity of continuous epidemical and epizootical monitoring of the new filovirus infection.

A new taxon of the subfamily Chordopoxvirinae that may represent a new genus of smallpox viruses is considered in this review. The distribution of gray squirrels (Sciurus carolinensis) throughout the UK during the 20th century and the decrease in the population of red squirrels (Sciurus vulgaris) is one of the most well-documented cases of ecological change of local fauna by the introduced species. The tendency to expand the distribution of the smallpox virus from Great Britain to the Western part of Europe has been noted. The genetic peculiarities of the genome of the poxvirus of squirrels, which determine its biological properties, as well as evolutionary relationships with other poxviruses, are separately described. Determination of the size of the genome by restriction analysis, sequencing of the whole genome, determination of the content of G/C nucleotide pairs, and functional mapping of the majority of genes made it possible to construct a phylogenetic tree. Phylogenetic analysis shows that this is a new representative of the subfamily Chordоpoxvirinae located between the viruses of the molluscum contagiosum and parapoxviruses. Serological and molecular biological methods are used to reveal and identify the causative agent of smallpox. The use of electron microscopy is limited in grey squirrels, due to the absence of organ damage and reproduction of the virus. Identification of the DNA of the causative agent of poxvirus of squirrels based on the use of different types of polymerase chain reaction (nested and in real time) overcomes all these limitations.

The brief review is devoted to description of the discovery of giant viruses belonging to the families of Mimiviridae and Marseilleviridae, as well as unassigned genera Pithoviruses, Pandoravirus, and Molliviruses. The review presents issues of their origin, evolution, and molecular-biological characteristics.

The reverse transcription - polymerase chain reaction method (RT-PCR) has leading position on diagnostic infections, caused by RNA-containing viruses. This method presents severe requirements to carrying out of everybody stages of analysis (extraction of nucleic acid, carry out reverse transcription, amplification of DNA). It is necessary to account the possibility of false positive or false negative results appearance. The use on RT-PCR only positive (PCS) and negative (NCS) control samples is insufficient for the control of stages of RNA extraction and reverse transcription. That is way there is necessity the construction of inner control sample (ICS) to control of these stages. The main goal of present is the ground of use genetic engineering constructions (GEC) as control samples (PCS and ICS) on evaluation of diagnostic kits for reveal of RNA of hazard and extremely hazard agents of virus infections by RT-PCR. The vector recombinant plasmids, containing the insertion of cDNA of agent´s genomic RNA are used as PCS, RNA was packed in membrane protein of MS2 bacteriophage, is used as ICS. It is demonstrated that ICS does no influence on sensitivity of RT-PCR both for use of native agents and for use of synthetic nucleic acids of Ebola, Marburg, Lassa, Machupo, Venezuelan encephalitis equine (VEE), Rift Valley fever and rabies viruses. The possibility of use of PCS and ICS for standardization of diagnostic kits is discussed., Competing Interests: The authors declare no conflict of interest.

Тhе kingdom Archaea, as well as Bacteria, belongs to the overkingdom Prokaryota. Halophilic archaea (Halorubrum lacusprofundi) isolated from Antarctic saline lakes contain plasmids (pR1SE) that code proteins taking part in the formation of membranes of archaea vesicles. The molecular and biological properties of pR1SE and the peculiarity of its interaction with sensitive cells are considered in this article. The role of structural proteins coded by pR1S in the process of formation of vesicle membrane complex is paid special attention. Plasmid-containing archaea vesicles model some properties of viruses. Archaea plasmids can be viewed as possible ancestors of DNA-containing viruses., Competing Interests: The authors declare no conflict of interest.

The Ebola virus disease (EVD) is one of the most dangerous infections affecting humans and animals. The first EVD outbreaks occurred in 1976 in Sudan and Zaire. Since then, more than 20 outbreaks have occurred; the largest of which (2014-2016) evolved into an epidemic in West Africa and claimed the lives of more than 11,000 people. Although vaccination is the most effective way to prevent epidemics, there was no licensed vaccine for EVD at the beginning of the latest outbreak. The development of the first vaccines for EVD started in 1980 and has come a long technological way, from inactivated to genetically engineered vaccines based on recombinant viral vectors. This review focuses on virus-vectored Ebola vaccines that have demonstrated the greatest efficacy in preclinical trials and are currently under different phases of clinical trial. Particular attention is paid to the mechanisms of immune response development, which are important for protection from EVD, and the key vaccine parameters necessary for inducing long-term protective immunity against EVD.

Severe fever with thrombocytopenia syndrome (SFTS) is an emerging infectious disease caused by a new virus (SFTS virus) reported to be endemic to central and northeastern parts of China. SFTS virus, which is classified into the genus Phlebovirus (the Bunyaviridae family), is suspected to be a tick-borne virus owing to evidence in two species of ticks: Haemaphysalis longicornis and Rhipicephalus microplus. SFTS virus is detected among many species of domestic animals in China. The clinical symptoms of SFTS include fever, thrombocytopenia, leucocytopenia, gastrointestinal symptoms, neural symptoms, bleeding tendency. The fatality rate of SFTS is 6-30%. Person-to-person transmission of SFTS virus is possible through blood contact. Clinical and epidemiological studies of SFTS, the cases of SFTS outside China, person-to-person transmission of SFTS virus, evolutionary and molecular analysis of the emergent SFTS virus, and risk assessment of human infection with a novel phlebovirus are considered in this review.

Ebola hemorrhagic fever, also known as Ebola virus disease or EVD, is one of the most dangerous viral diseases in humans and animals. In this open-label, dose-escalation clinical trial, we assessed the safety, side effects, and immunogenicity of a novel, heterologous prime-boost vaccine against Ebola, which was administered in 2 doses to 84 healthy adults of both sexes between 18 and 55 years. The vaccine consists of live-attenuated recombinant vesicular stomatitis virus (VSV) and adenovirus serotype-5 (Ad5) expressing Ebola envelope glycoprotein. The most common adverse event was pain at the injection site, although no serious adverse events were reported. The vaccine did not significantly impact blood, urine, and immune indices. Seroconversion rate was 100 %. Antigen-specific IgG geometric mean titer at day 42 was 3,277 (95 % confidence interval 2,401-4,473) in volunteers immunized at full dose. Neutralizing antibodies were detected in 93.1 % of volunteers immunized at full dose, with geometric mean titer 20. Antigen-specific response in peripheral blood mononuclear cells was also detected in 100 % of participants, as well as in CD4+ and CD8+ T cells in 82.8 % and 58.6 % of participants vaccinated at full dose, respectively. The data indicate that the vaccine is safe and induces strong humoral and cellular immune response in up to 100 % of healthy adult volunteers, and provide a rationale for testing efficacy in Phase III trials. Indeed, the strong immune response to the vaccine may elicit long-term protection. This trial was registered with grls.rosminzdrav.ru (No. 495*), and with zakupki.gov.ru (No. 0373100043215000055).

Lujo hemorrhagic fever (LHF) is a viral disease accompanied with fever, headache, vomiting, diarrhea, arthralgia, myalgia and numerous signs of hemorrhagic syndrome. LHF causes a clinical syndrome remarkably similar to Lassa hemorrhagic fever. The first case of LHF occurred in Johannesburg, South Africa, in 2008. There was a secondary transmission from the index patient to four healthcare workers. Four of the five patients died. The etiologic agent of LHF is Lujo virus (LUJV) belonging to Arenavirus genus of the Arenaviridae Family. Virus Lujo is the second pathogenic arenavirus, after Lassa virus, to be recognized in Africa during the last 40 years. Data about epidemiology, clinical characteristics and diagnostics of LHF, properties of Lujo virus (according to phylogenetic analysis), and recommended precautions for preventing secondary transmission are considered in this paper., Competing Interests: The authors declare no conflict of interest.

The aim of this work was to estimate the efficacy and safety of single intramuscular introduction of specific heterologous immunoglobulin as prophylactic drug against Ebola hemorrhagic fever. Materials and methods. The specific heterologous immunoglobulin was introduced as a special prophylactic drug to 28 patients in epidemic situations, after skin hurt with infectious materials or contact with infectious blood. Clinico-laboratory observation was performed in 24 subjects after single intramuscular introduction of heterologous immunoglobulin Ebola. The samples of blood serum were investigated for immunoglobulin Ebola and antibodies to horse gamma-globulin on the 30th and 60th days after prophylaxis. Results. None of the subjects of the study contracted Ebola fever. There were no anaphylactic reactions after special prophylaxis with specific heterologous immunoglobulin. Among the subjects with normal allergic state 31% responded with local reactions; 13%, with a general reaction (mild case of the serum disease). Almost no reaction was observed in patients with unfavorable allergic state subjected to desensitizing therapy; in the absence of desensitizing therapy, 50% of patients with unfavorable allergic state exhibited local reactions; 17%, mild cases of the serum disease; 33%, moderate cases of the serum disease. In summary, if the tactics of immunoglobulin application was right, the quantity of local allergic reactions was 28%; of wide spread reactions, 6%. Weak serum disease was observed in 11% of the subjects. The prognostic period of resistance to Ebola fever was less than 30 days. Conclusion. The prophylactic use of specific immunoglobulin from horse blood serum against hemorrhagic Ebola fever is effective and relatively safe in patients subjected to desensitizing therapy.

Aim: Determination of values of coefficients of thermal stability of TEOVac for prognosis of conservation of the vaccine (specific biological activity) during the process of warranty period storage., Materials and Method: TEOVac (masticatory tablets) in primary packaging was kept at increased temperature (accelerated and stress-tests) and at the conditions established by PAP for the preparation (long-term tests). Biological activity of the vaccine was determined by titration on 12-day chicken embryos., Results: A correlation between the value of coefficients of thermal stability and conservation of the prepared series of the condition preparation at the final date of storage was experimentally established., Conclusion: Coefficients of thermal stability could be used as a prognostic indicator of quality of the produced pelleted formulation of the preparation for evaluation of conservation of the vaccine during warranty period storage.

Buffalopox is a contagious viral disease affecting milch buffaloes (Bubalus Bubalis) and, rarely, cows. The disease has zoonotic implications, as outbreaks are frequently associated with human infections, particularly in the milkers. Buffalopox is associated with high morbidity (80%). The clinical symptoms of the disease are characterized by wartline lesions on the udder, teats, inguinal region, base of the ears, and over the parotid. In the severe form, generalized rash is observed. Although the disease does not lead to high mortality, it has an adverse effect on the productivity and working capacity of the animals resulting in large economic losses. The outbreaks of buffalopox occurred frequently in India, Pakistan, Bangladesh, Nepal, Iran, Egypt, and Indonesia, where buffaloes are reared as milch animals. The buffalopox is closely related with other Orthopoxviruses. In particular, it is close to the vaccinia virus. There is a view that the buffalopox virus might be derived from the vaccinia virus. It is possible that it became pathogenic to humans and animals through adaptive evolution of the genome by obtaining the virulence genes. PCR is performed for the C18L gene for the purpose of specific detection and differentiation of the buffalopox virus from other orthopoxviruses. The C18L gene encodes the ankyrin repeat protein, which determines the virus host range. The open reading frame of this gene is only 150-nucleotide long as against 453 nucleotide in the vaccinia virus, 756 - in the camelpox virus, and 759 - in the cowpox virus. It can be concluded that a systematic study based on the epidemiology of the virus, existence of reservoirs, biological transmission, and the molecular organization of the buffalopox virus from buffalo, cow, and humans may pave the way to a better understanding of the circulating virus and contribute to the control of the disease using the suitable diagnostic and prophylactic measures.

Aim: Detection-and identification of Venezuelan equine encephalomyelitis (VEE) virus RNA in biological samples by reverse-transcription polymerase chain reaction (RT-PCR) and RT-PCR in real time (rRT-PCR)., Materials and Methods: VEE, Sindbis, West Nile, Japanese and tick-borne encephalitis viruses were studied. Cell culture of chicken fibroblasts, outbred mice and rats, Javanese macaques were used in the experiments. Biological activity determination of the running culture of causative agents used in the experiments was carried out by negative colony method in monolayer cell culture under agar coating. and using intra-cerebral infection of mice. Reagent kits developed in the 48th Central Research Institute and Institute of Analytical Instrument Engineering were used during execution of experiments of VEE virus RNA detection by RT-PCR and rRT-PCR., Results: VEE virus was detected in biological samples by various methods. Data from RT-PCR and rRT-PCR are in accordance with the results of virus detection in samples using sensitive animals., Conclusion: Use of molecular-diagnostics methods for detection in biological samples of a causative agent of a dangerous infectious disease is important for procuring biological safety of Russian Federation.

Aim: Experience of study and possible ways of elimination of false positive and false negative results during execution of polymerase chain reaction on an example of Junin virus RNA detection. MATERIALSS AND METHODS: Junin virus--causative agent of Argentine hemorrhagic fever (AHF) strain XJpR37/5787 was obtained from the State collection of pathogenicity group I causative agents of the 48th Central Research Institute. Reagent kit for detection of Junin virus RNA by RT-PCR was developed in the Institute and consists of 4 sets: for isolation of RNA, execution of reverse-transcription reaction, execution of PCR and electrophoretic detection of PCR products. RT-PCR was carried out by a standard technique. Continuous cell cultures of African green monkey Vero B, GMK-AH-1(D) were obtained from the museum of cell culture department of the Centre., Results: An experimental study of the effect of various factors of impact on the sample under investigation ("thawing-freezing", presence of formaldehyde, heparin) on the obtaining of false negative results during Junin virus RNA detection by using RT-PCR was studied. Addition of 0.01% heparin to the samples was shown to completely inhibit PCR. Addition of 0.05% formaldehyde significantly reduces sensitivity of the method. A possibility of reduction of analysis timeframe from 15 to 5 days was shown during detection of the causative agent in samples with low concentration of the latter by growing the samples and subsequent analysis of the material obtained by using RT-PCR., Conclusion: During detection of causative agent by using RT-PCR false negative results could appear in the presence of formaldehyde and heparin in the sample. A possibility of elimination of false negative PCR results due to concentration of the causative agent in the sample under investigation at a level below sensitivity threshold was shown on the example of Junin virus RNA detection by using growing of the pathogen in appropriate accumulation system with subsequent analysis of the material obtained using PCR.