Search

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.

The emergence of the novel henipavirus, Langya virus, received global attention after the virus sickened over three dozen people in China. There is heightened concern that henipaviruses, as respiratory pathogens, could spark another pandemic, most notably the deadly Nipah virus (NiV). NiV causes near-annual outbreaks in Bangladesh and India and induces a highly fatal respiratory disease and encephalitis in humans. No licensed countermeasures against this pathogen exist. An ideal NiV vaccine would confer both fast-acting and long-lived protection. Recently, we reported the generation of a recombinant vesicular stomatitis virus–based (rVSV-based) vaccine expressing the NiV glycoprotein (rVSV-ΔG-NiVBG) that protected 100% of nonhuman primates from NiV-associated lethality within a week. Here, to evaluate the durability of rVSV-ΔG-NiVBG, we vaccinated African green monkeys (AGMs) one year before challenge with an uniformly lethal dose of NiV. The rVSV-ΔG-NiVBG vaccine induced stable and robust humoral responses, whereas cellular responses were modest. All immunized AGMs (whether receiving a single dose or prime-boosted) survived with no detectable clinical signs or NiV replication. Transcriptomic analyses indicated that adaptive immune signatures correlated with vaccine-mediated protection. While vaccines for certain respiratory infections (e.g., COVID-19) have yet to provide durable protection, our results suggest that rVSV-ΔG-NiVBG elicits long-lasting immunity.

Objective. Selection of indicators of lymphocyte populations in rhesus macaques determined by flow cytometry to evaluate variations of cellular constituent of their immune status.Materials and methods. Blood of 11 healthy rhesus macaque males, 2,0–2,5 years old, weighing 2,5–3,0 kg, was used. Monkeys were examined simultaneously in each of 7 months of observation (since May till November). Immunophenotyping was conducted by FC500 cytofluorimeter using Affymetrix eBioscience monoclonal antibodies. The following cellular constituent indicators of immune status were differentiated: total T lymphocytes (phenotype CD2+CD20-); total B lymphocytes (phenotype CD2-CD20+); natural killer cells (phenotype CD2+CD56+); T helper cells (phenotype CD2+CD4+); cytotoxic T lymphocytes (phenotype CD2+CD8+); double-positive T lymphocytes (phenotype CD4+CD8+) and T lymphocytes positive by antigens CD2 and CD20 (phenotype CD2+CD20+).Results and discussion. Statistical analysis of the obtained results revealed the absence of the effect of research time factor on the stated indicators. To assess changes in the cellular constituent of immune status of rhesus macaques, it is possible to use indicators that are less variable: total T and B lymphocytes, T helper cells, cytotoxic T lymphocytes and T lymphocytes with phenotype (CD2+CD20+). The use of CD56 as a marker of natural killer cells of rhesus macaques is impractical due to its low expression and a small size of the population bearing this marker. The research results may form the basis of the normative indicators of the subpopulation cell composition of immune system in rhesus macaques, which will allow the study of infected animals when assessing the quality of medical products in relation to dangerous and particularly dangerous infections.

The main triggers of new infectious diseases, including those with pandemic potential, are: spontaneous emergence of infectious strains which are more virulent for humans and contribute to transmission of pathogenic microorganisms, environmental changes, social and economic factors, increased contact rates between different regions. A successful pandemic response requires mass immunisation against a specific disease, aimed at the development of herd immunity which is based on the concept of indirect protection of the whole of the population by immunising a part of it. A well-grounded choice of the vaccine platform is central to dealing with this problem. The aim of the study was to compare characteristics of vaccine platforms (attenuated, inactivated, subunit, recombinant vector, DNA, and RNA vaccines) intended for mass immunisation against dangerous and extremely dangerous viral infections with pandemic potential. The study focused on the members of Poxviridae, Orthomyxoviridae and Coronaviridae families as potential pathogens. The vaccine platforms were compared in terms of the following parameters: capability of producing a robust immune response; protective efficacy; time required for vaccine development and testing; ability to produce vaccine in volumes required for mass immunisation; potential obstacles associated with the intended use of the vaccine. It is expected that in the next few decades DNA and RNA vaccine platforms will be most widely used for development of products against dangerous and extremely dangerous viral infections with pandemic potential, regardless of taxonomic groups of pathogens.

Epidemic vector-borne viral infections pose a serious threat to public health worldwide. There is currently no specific preventive treatment for most of them. One of the promising solutions for combating viral fevers is development of vector vaccines, including MVA-based vaccines, which have virtually no adverse side effects. The safety of the MVA strain and absent reactogenicity of recombinant MVA vaccines have been supported by many clinical trials.The article focuses on test results for similar preventive products against viral fevers: Crimean-Congo hemorrhagic fever, Rift Valley fever, yellow fever, Chikungunya and Zika fevers.Their immunogenicity was evaluated on immunocompetent and immunocompromised white mice; their protective efficacy was assessed on immunocompromised white mice deficient in IFN-α/β receptors, that are used for experimental modeling of the infection. Nearly all the new recombinant vaccines expressing immunodominant antigens demonstrated 100% protective efficacy. It has been found that although the vaccine expressing Zika virus structural proteins induced antibodies against specific viral glycoproteins, it can be associated with high risks when used for prevention of Zika fever in individuals who had dengue fever in the past, due to the phenomenon known as antibody-dependent enhancement of infection, which can occur in diseases caused by antigenically related flaviruses. For this reason, the vaccine expressing non-structural protein 1 (NS1) was developed for vaccination against Zika fever.The yellow fever vaccine developed on the MVA platform had immunogenicity similar to that of the commercial 17D vaccine, outperforming the latter in safety.

The pandemic of the new coronavirus (COVID-19) disease that began in December 2019 in China is still having a huge impact on all spheres of human life. The herd immunity, which is the most effective tool for preventing the spread of the disease, is formed in two ways: the passive way (i.e., the formation of a population not susceptible to re-infection due to the natural spread of the disease) and the active way (mass immunisation). High rates of COVID-19 vaccination were achieved thanks to the development and mass production of new vaccines. The selection of the most promising vaccine platforms is one of the key aspects of successful mass immunisation. The aim of the study was to compare the characteristics of COVID-19 vaccines used for mass immunisation. The paper analyses the vaccine technology platforms, efficacy of different types of vaccines based on clinical trial results, safety of vaccines for different population groups, and potential for scaling up vaccine production in order to ensure the necessary vaccination coverage. The vaccines currently used for mass immunisation are: BNT162b2 (Pfizer/BioNTech), mRNA1273 (Moderna), Gam-COVID-Vac (N.F. Gamaleya National Research Center for Epidemiology and Microbiology), Ad26.COV2.S (Johnson & Johnson), ChAdOx1-S (AZD1222) (AstraZeneca), BBIBP-CorV (Sinopharm), CoronaVac (Sinovac Biotech), and NVX-CoV2373 (Novavax). The comparison of the main characteristics of the vaccines demonstrated that the most promising types of vaccines for COVID-19 specific prophylaxis are RNA vaccines and recombinant adenovirus vector-based vaccines.

Although successes in antiretroviral therapy (ART) turned AIDS from lethal illness into sluggishly progressing disease, its prevention and treatment remain one of the most socially significant concerns. The increase in the number of patients infected with human immunodeficiency virus (HIV), especially in the USA, South America and Europe, determines the need in creating a vaccine against this disease. Existing vaccination practice has demonstrated efficiency of priming/boosting scheme for the development of immune responses. As anti-vector immunity of priming vector can constrain the response to boosting immunization with the same vaccine, heterologous priming/boosting vector constructs are used. An ideal AIDS vaccine would prevent virus dissemination and control viral replication, but it also must be safe for HIV-infected contingent. The vaccination of HIV-infected individuals is used for enhancing immune-mediated elimination of persistently HIV-infected CD4+ Т-cells during long-term ART in order to purge the latently infected viral reservoirs. The paper considers the results of clinical trials of DNA-anti-HIV/AIDS vaccines and recombinant MVA strain of vaccinia virus, expressing different combination of HIV genes, which demonstrated the safety and tolerability both, in HIV-infected and non-HIV-infected volunteers. All implemented schedules of vaccination induced cell-mediated and humoral immune responses in all volunteers. And though there are no data on acquiring AIDS by HIV-uninfected volunteers from groups at low risk of HIV-infection, there are no grounds to conclude the sufficiency of induced protection for the prevention of possible HIV infection.

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%.

Antibody-dependent enhancement (ADE) is a phenomenon where virus-specific antibodies paradoxically cause enhanced viral replication and/or excessive immune responses, leading to infection exacerbation, tissue damage, and multiple organ failure. ADE has been observed in many viral infections and is supposed to complicate the course of COVID-19. However, the evidence is insufficient. Since no specific laboratory markers have been described, the prediction and confirmation of ADE are very challenging. The only possible predictor is the presence of already existing (after previous infection) antibodies that can bind to viral epitopes and promote the disease enhancement. At the same time, the virus-specific antibodies are also a part of immune response against a pathogen. These opposite effects of antibodies make ADE research controversial. The assignment of immunoglobulins to ADE-associated or virus neutralizing is based on their affinity, avidity, and content in blood. However, these criteria are not clearly defined. Another debatable issue (rather terminological, but no less important) is that in most publications about ADE, all immunoglobulins produced by the immune system against pathogens are qualified as pre-existing antibodies, thus ignoring the conventional use of this term for natural antibodies produced without any stimulation by pathogens. Anti-glycan antibodies (AGA) make up a significant part of the natural immunoglobulins pool, and there is some evidence of their antiviral effect, particularly in COVID-19. AGA have been shown to be involved in ADE in bacterial infections, but their role in the development of ADE in viral infections has not been studied. This review focuses on pros and cons for AGA as an ADE trigger. We also present the results of our pilot studies, suggesting that AGAs, which bind to complex epitopes (glycan plus something else in tight proximity), may be involved in the development of the ADE phenomenon.

The virucide activity of Monclavit-1 against the influenza virus A/Chicken/Kurgan/2/Russia/05 (H5N1) was investigated in the MDCK cell culture. It was shown that at a temperature of 14.0±1.0°C Monclavit-1 in a 20-fold dilution within an hour inactivated the cytopathic activity of the virus and the specific hemagglutinin generation by 100 and 87.5% respectively. In a 40-fold dilution it inactivated at the average by 50% both the cytopathic activity and the specific hemagglutinin generation. In an 80-fold dilution it inactivated the cytopathic activity at the average by 20%. In a 160-fold dilution it did not inactivate the pathogen. At a temperature of 25.0±1.0°C Monclavit-1 inactivated the influenza virus A/Chicken/Kurgan/2/Russia/05 (H5N1) by 90.0% only in the highest concentration.

Analysis of the efficacy of Grippferon vs. the reference drugs Realdiron and Reaferon-EC against the influenza virus A(H1N1)/2009 in susceptible static cell cultures showed that in the concentrations tested it was efficient in inhibition of the virus cytopathic activity and generation of specific hemagglutinin.

High in vitro and in vivo efficacy of Ingavirin® against the Mexican pandemic influenza virus A/H1N1/2009, strains A/California/ 04/2009 (H1N1) and A/California/07/2009 (H1N1) vs. the reference drug Arbidol® was studied and verified when used therapeutically and prophylactically.

Zika virus (ZIKV) is a representative of the viruses of the genus Flavivirus in the family Flaviviridae, it belongs to the zoonotic arbovirus infections transmitted by mosquitoes of the genus Aedes. In humans, this flavivirus causes a disease known as zika fever, etymologically related to yellow fever, dengue, West Nile and Chikungunya viruses. There is no specific treatment for zika fever, just as there is no vaccine or preventive measures available to date. A comparative analysis of the effectiveness of chemotherapy medications, interferon inducers and two classes of interferon α-, β-, and γ- showed that interferon drugs effectively inhibit the reproduction of Zika virus in Vero cell culture in a wide range of concentrations. Chemotherapy medications Triazavirin®, Virazole®, Zovirax®, Cytarabine®, and Ingavirin® did not affect the reproduction of Zika virus strain MR 766V in Vero cell culture. The size of negative Zika virus colonies was significantly reduced in the presence of Virazole® and Ribavirin® at a concentration of 100 μg/ml. zika virus, Triazavirin®, Ribavirin®, Ingavirin®, Reaferon-EU®, Rebif(fila)®, antiviral efficacy

Ebola outbreak in eastern parts of the Democratic Republic of the Congo in 2018–2020 proved that the virus remains highly hazardous for humans, and the outbreak in West Africa in 2014–2016, which was the largest Ebola outbreak in history, showed that it could be imported to other continents, including Russia. In 1993 the Federal State Budgetary Institution “48th Central Scientific Research Institute” of the Russian Ministry of Defence developed a specific equine immunoglobulin for emergency prophylaxis of Ebola in risk groups. The evaluation and improvement of the product’s properties is an important area in the development of biological defence technologies.The aim of the study was to examine the properties of the equine anti-Ebola immunoglobulin which had been stored for a long time at 2–8 °C.Materials and methods: the authors studied batches of heterologous anti-Ebola immunoglobulin that had been stored for 17–22 years. The properties of the product were evaluated according to the requirements of the State Pharmacopoeia of the Russian Federation, 14th ed. (Ph. Rus. 14 ed.). The specific activity of the product was determined in a plaque reduction neutralisation test using Ebola virus and African green monkey kidney cells (GMK-AH-1(D)). Immunoglobulin molecular parameters were determined by size-exclusion high-performance liquid chromatography using the test methods described in the European Pharmacopoeia 9.6 and Ph. Rus. 14 ed.Results: the storage of anti-Ebola immunoglobulin for 17–22 years at 2–8 °C resulted in a four-fold reduction of the level of virus-neutralising antibodies against Ebola, decrease in the proportion of monomers from 98 to 74–90%, increase in the proportion of dimers and polymers, and formation of immunoglobulin molecules’ fragments. Signs of toxicity for mice were observed in one of the three product batches. Conclusions: the obtained results suggest the need to perform more studies to test the quality of antiEbola immunoglobulin batches that were stored for shorter periods of time in order to assess the stability of their initial characteristics.

The review considers the relevant aspects of laboratory diagnosis of rabies. The methods of laboratory diagnostics of rabies infection, standardized by WHO in 2018, and their use in the Russian Federation are presented. The scheme of laboratory diagnostics of rabies, applied by specialists of the “48th CRI” of the Ministry of Defense of Russia, for the study of biological samples from deceased people is outlined. Between 2002 and 2018, the study of biomaterial was carried out using molecular-biological, virological methods of diagnosis and in some cases electron microscopy, which allowed to detect and identify the pathogen in 257 samples from 71 people, to certify and deposit new isolates of the rabies virus. Accumulation and analysis of the lessons learned in the application of molecular-biological method of rabies diagnosis allows us to recommend the use of RT-PCR, real-time RT-PCR sets (having a certificate of state registration) in healthcare and veterinary medicine practice to identify the causative agent of rabies infection. The use of molecular-biological methods is promising in terms of the development of rabies diagnosis to improve epidemiological surveillance and raise the efficiency of the biological protection of the population of the Russian Federation.

A wealth of fascinating phenomena have been discovered at the BiFeO3 domain walls, examples such as domain wall conductivity, photovoltaic effects, and magnetoelectric coupling. Thus, the ability to precisely control the domain structures and accurately study their switching behaviors is critical to realize the next generation of novel devices based on domain wall functionalities. In this work, the introduction of a dielectric layer leads to the tunability of the depolarization field both in the multilayers and superlattices, which provides a novel approach to control the domain patterns of BiFeO3 films. Moreover, we are able to study the switching behavior of the first time obtained periodic 109° stripe domains with a thick bottom electrode. Besides, the precise controlling of pure 71° and 109° periodic stripe domain walls enable us to make a clear demonstration that the exchange bias in the ferromagnet/BiFeO3 system originates from 109° domain walls. Our findings provide future directions to study the room temperature electric field control of exchange bias and open a new pathway to explore the room temperature multiferroic vortices in the BiFeO3 system.

The introduction of SARS-CoV-2 coronavirus from a natural reservoir into the human population subsequently caused the COVID-19 pandemic, that had a huge impact on all spheres of human activity dramatically increased interest in this group of viruses. Given that such an introduction of the coronavirus was already the third in a row in 21 century (after outbreaks caused by SARS-CoV and MERS-CoV viruses), there are quite good reasons to fear the appearance of new diseases, the etiological agents of which will be representatives of the Coronaviridae family in the future. The purpose of this review is to assess the potential risk of coronaviruses of animals as possible human pathogens. When preparing the review, the following data were used: data published in leading foreign journals as well as in Internet sources that address some aspects of the COVID-19 pandemic. The following main aspects of this problem are considered: a spontaneous formation during the evolution of animal coronaviruses, highly pathogenic to humans; a possibility of transmission of human coronavirus to animals, its genetic interaction with the coronavirus, the owner of which is this animal, the acquisition of viral progeny, a set of new properties and reverse transmission from animal to man a pathogen that may have increased pathogenicity. Animal coronaviruses are considered by belonging to a certain taxonomic group of their natural hosts. The main focus is on bat coronaviruses (as a reservoir of SARS-CoV, MERS-CoV and SARS-CoV-2 viruses), as well as avian coronaviruses, due to the potential ability of these animals to become vectors of spread of new emergent diseases and the coronaviruses of carnivores, due to the established during the COVID-19 pandemic fact of transmission of the SARS-CoV-2 virus from man to mink and from mink to man. Studying the features of molecular evolution it will help you better understand the mechanisms of occurrence and adaptation to humans pathogens of emergent viral diseases.

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.