LIVE ANTIVARIOLIC VACCINES

Smallpox eradication due to global vaccination is still one of the paramount triumphs of medical science. Given the termination of the subsequent immunization, nowadays humanity virtually possesses no antivariolic immunity and is unprotected against the pathogenic for humans orthopoxviruses. Utilization of the first-generation traditional live vaccines, obtained with the help of the virus replication on calf skin, or the second-generation preparation, produced in mammalian cell cultures or grown on bird embryos, for mass vaccination is currently unacceptable in view of considerable increase in immune deficiency states among the human population within the recent decades. Attenuated non-replicating antivariolic vaccines of the third generation, obtained in the process of multiple vaccinia virus (VV) passage on cell cultures of heterologous host, induce weaker antivariolic response as compared to traditional vaccine. The most prospective approach is to produce the vaccines of the fourth generation, applying targeted VV genes’ mutation, which control protective reactions of an organism against viral infection, as well as host range genes and the genes involved in nucleic acid metabolism, while skipping the genes responsible for virus replication. Novel attenuated and highly immunogenic strain, VV LIVPΔ6, having mutations in 6 virulence genes, is presently in the phase of pre-clinical trial and later on it may turn an effective and safe vaccine of the fourth generation against smallpox and other orthopoxvirus infections in humans

Complex Approach to Species-Specific Detection of Cowpox Virus

Objective of the study is to develop and validate the method for species-specific detection of cowpox virus (CPV). Materials and methods. Utilized were oligonucleotide primers and fluorescence-labeled probes for genus-specific detection of orthopoxviruses (OPV) and species-specific detection of cowpox and ectromelia viruses (EV). Pairs of fluorescent dyes and corresponding fluorescence extinguishers were embodied into probes in accordance with their specificity: OPV-specific probe contained FAM/BHQ1 pair, CPVspecific probe – JOE/BHQ1, and EV-specific – Cy5/BHQ3. For evaluation of sensitivity and specificity of the method for species-specific detection of CPV, investigated were samples of 68 different strains of orthopoxviruses. Results and conclusions. Implemented was complex approach to species-specific detection of CPV using multiplex real-time PCR variant for simultaneous multilocus detection on the basis of three independent target genes of CPV, to genus-specific detection for the exclusion of false-negative results, and additional oligonucleotide primers and probes, providing for specific detection of EV, aimed at the exclusion of false-positive results

Orthopoxvirus Infections: Epidemiology, Clinical Picture, and Diagnostics (Scientific Review)

Lack of immunity among the population against pathogenic orthopoxviruses and an increased number of these infections human cases testify to the need of development of the rapid high-sensitive methods for species-specific orthopoxvirus diagnostics. The review presents current epidemiological situation on human orthopoxvirus infections. Addressed are clinical aspects of the disease, caused by small pox virus (SPV), Monkeypox virus, cowpox virus, and vaccinia virus. Represented is a historical survey of the conventional methods for diagnostics of these particular viruses. Reconsidered are the benefits of researches into the sphere of state-of-the-art molecular-diagnostic techniques taking into view both genus-specific and species-specific detection of agents, causing orthopoxvirus infections in humans. Demonstrated is the urgency of new-generation typing in view of occurrence of a novel SPV-like virus emerged as a result of natural evolution of existing zoonotic orthopoxviruses or SPV application as a biological terroristic agent

A Decadal Inversion of CO2 Using the Global Eulerian-Lagrangian Coupled Atmospheric Model (GELCA): Sensitivity to the Ground-Based Observation Network

We present an assimilation system for atmospheric carbon dioxide (CO2) using a Global Eulerian-Lagrangian Coupled Atmospheric model (GELCA), and demonstrate its capability to capture the observed atmospheric CO2 mixing ratios and to estimate CO2 fluxes. With the efficient data handling scheme in GELCA, our system assimilates non-smoothed CO2 data from observational data products such as the Observation Package (ObsPack) data products as constraints on surface fluxes. We conducted sensitivity tests to examine the impact of the site selections and the prior uncertainty settings of observation on the inversion results. For these sensitivity tests, we made five different sitedata selections from the ObsPack product. In all cases, the time series of the global net CO2 flux to the atmosphere stayed close to values calculated from the growth rate of the observed global mean atmospheric CO2 mixing ratio. At regional scales, estimated seasonal CO2 fluxes were altered, depending on the CO2 data selected for assimilation. Uncertainty reductions (URs) were determined at the regional scale and compared among cases. As measures of the model-data mismatch, we used the model-data bias, root-mean-square error, and the linear correlation. For most observation sites, the model-data mismatch was reasonably small. Regarding regional flux estimates, tropical Asia was one of the regions that showed a significant impact from the observation network settings. We found that the surface fluxes in tropical Asia were the most sensitive to the use of aircraft measurements over the Pacific, and the seasonal cycle agreed better with the results of bottom-up studies when the aircraft measurements were assimilated. These results confirm the importance of these aircraft observations, especially for constraining surface fluxes in the tropics

Cases of Orthopoxviral Infections around the World over a Period of 2008–2018

The eradication of smallpox has become one of the greatest successes of modern health science. This great achievement was made possible thanks to the widespread vaccination of the population. The last case of human infection with smallpox virus occurred in 1977. In 1980, at the 33rd session of the World Health Assembly, routine vaccination against that infection was recommended to be discontinued due to severe post-vaccination complications. However, humanity remains vulnerable to other orthopoxvirus infections closely related to smallpox virus. Recently, the cases of human infection with ortopoxviruses such as monkeypox virus, cowpox virus, vaccinia virus have become more frequent. Also, cases of infection of people with previously unknown orthopoxvirus species are recorded. Zoonotic orthopoxviruses pathogenic for humans, circulating in nature, require a detailed study and monitoring of the emergence of new strains. Their occurrence against the background of the cessation of planned vaccination of the population against smallpox virus can lead to the emergence of new highly pathogenic viruses. This review contains information on cases of human infection with orthopoxviruses around the world for the period 2008–2018. It also describes epidemiological anamnesis and the relations between cases of human infection in different countries due to the spread of viruses over a wide area, the movement of people between countries, population contacts with domestic and wild animals. Also, this paper provides information on the infection of people with previously unknown strains of orthopoxviruses

A comparative study of replicative properties of antitumor recombinant vaccinia viruses on human glioblastoma cell culture U87 and monkey kidney cell culture CV-1

In the world of today, virotherapy is one of the rapidly developing areas in the treatment of cancer, and its advantage is selective destruction of cancer cells with minimizing the destructive effect on normal cells of the body. A promising basis for the creation of oncolytic drugs is orthopoxviruses, which have a number of advantages over other viral vectors, and one of these advantages is a large capacity of the genome, which allows genes encoding proteins with antitumor properties to be cloned into their genome. In this study, we compared the replicative properties of ten variants of vaccinia virus (the strain LIVP of VACV) using human glioblastoma cell culture; some of these viruses have additional genes, such as the gene encoding granulocyte-macrophage colony stimulating factor, gene encoding apoptosis-inducing protein TRAIL and gene encoding green fluorescent protein. Furthermore, the virus with five virulence genes deleted (genes encoding hemagglutinin, γ-interferonbinding protein, thymidine kinase, complementbinding protein and Bcl2-like inhibitor of apoptosis), which has significantly lower reactogenicity and neurovirulence compared to the original strain LIVP of VACV, was studied. These data suggest that variants of vaccinia virus with a defective gene encoding thymidine kinase most actively replicate in glioblastoma cell culture

Obtainingvaccinia virus with increased production of extracellular enveloped virions and directing GM-CSF synthesis as a promising basis for development of antitumor drug

The problems of oncological disease treatment are considered relevant and timely issues of the current research programs. Since monotherapy is increasingly clear to be less effective than combination therapy, the novel studies seek for advancement of current treatments and development of new ones employing oncolytic immunotherapy being among the most rapidly evolving approaches. Modern genetic engineering techniques enable new applications of oncolytic viruses in the frames of combined cancer therapy. These applications are feasible, due to the abilities of oncolytic viruses to destruct tumor cells, like as by changing susceptibility of cancer cells to anti-tumor drug, and upon the whole body, thus overcoming the mechanisms conferring immunoresistance of tumor cells. In the present work, we have developed a recombinant vaccinia virus which is a promising platform for designing the antitumor drugs. The following modifications of viral genome were made by means of genetic engineering: gene encoding granulocyte-macrophage colony-stimulating factor was inserted into the region of viral thymidine kinase gene; viral A34R gene encoding a membrane glycoprotein, was replaced by A34R gene with two nucleotide substitutions resulting into D110N and K151E mutations which cause increased proportion of extracellular enveloped virions during the virus reproduction. Some properties of the recombinant virus were studied in vitro. The virus was shown to produce granulocyte-macrophage colony stimulating factor, and high numbers of extracellular enveloped virions. The genome modifications had no effect upon viral replication

Viability of sARs-CoV-2 Coronavirus strains on Different types of test surfaces, in Drinking Water and Their Resistance to Disinfectants

The purpose of the research was to study the dynamics of residual infectious activity of SARS-CoV-2 virus strains belonging to different genovariants, on different types of surfaces, in samples of drinking dechlorinated water at 24–28 °C, as well as their resistance to disinfectants.Materials and methods. The studies were carried out using SARS-CoV-2 coronavirus strains obtained from the State Collection of Causative Agents of Viral Infectious Diseases and Rickettsiosis, which operates at the premises of the SSC VB “Vector”. The evaluation of the residual infectivity of the SARS-CoV-2 coronavirus was carried out through titration of samples in cell culture.Results and discussion. The conducted studies have confirmed the ability of all investigated strains of the SARS-CoV-2 coronavirus to maintain their infectious activity at 24–28 °C on most of the examined types of test surfaces for at least 48 hours, while the virus is best preserved on stainless steel and plastic. All studied strains of the SARS-CoV-2 coronavirus are viable in drinking dechlorinated water for at least 48 hours. In addition, it has been found that all of them are sensitive to disinfectants of different groups, widely used for disinfection when working with pathogenic biological agents or for treating hands and surfaces contaminated with viruses. Chlorine-containing disinfectants are the most active. Skin antiseptics based on ethyl and isopropyl alcohols are suitable for disinfecting hands and objects contaminated with the SARS-CoV-2 virus

Regional CO2 flux estimates for 2009-2010 based on GOSAT and ground-based CO2 observations

We present the application of a global carbon cycle modeling system to the estimation of monthly regional CO2 fluxes from the column-averaged mole fractions of CO2 (XCO2) retrieved from spectral observations made by the Greenhouse gases Observing SATellite (GOSAT). The regional flux estimates are to be publicly disseminated as the GOSAT Level 4 data product. The forward modeling components of the system include an atmospheric tracer transport model, an anthropogenic emissions inventory, a terrestrial biosphere exchange model, and an oceanic flux model. The atmospheric tracer transport was simulated using isentropic coordinates in the stratosphere and was tuned to reproduce the age of air. We used a fossil fuel emission inventory based on large point source data and observations of nighttime lights. The terrestrial biospheric model was optimized by fitting model parameters to observed atmospheric CO2 seasonal cycle, net primary production data, and a biomass distribution map. The oceanic surface pCO2 distribution was estimated with a 4-D variational data assimilation system based on reanalyzed ocean currents. Monthly CO2 fluxes of 64 sub-continental regions, between June 2009 and May 2010, were estimated from GOSAT FTS SWIR Level 2 XCO2 retrievals (ver. 02.00) gridded to 5° � 5° cells and averaged on a monthly basis and monthly-mean GLOBALVIEW-CO2 data. Our result indicated that adding the GOSAT XCO2 retrievals to the GLOBALVIEW data in the flux estimation brings changes to fluxes of tropics and other remote regions where the surface-based data are sparse. The uncertainties of these remote fluxes were reduced by as much as 60 through such addition. Optimized fluxes estimated for many of these regions, were brought closer to the prior fluxes by the addition of the GOSAT retrievals. In most of the regions and seasons considered here, the estimated fluxes fell within the range of natural flux variabilities estimated with the component models

Overview of the Situation on Highly Pathogenic Avian Influenza Virus H5 in Russia in 2016–2017

In 2016–2017, several outbreaks among wild and domestic birds caused by highly pathogenic influenza virus were recorded in the territory of the Russian Federation. After isolation of the highly pathogenic influenza A (H5N8) virus in the territory of the Republic of Tyva in May 2016, the virus was introduced into the west by wild birds, where it caused a massive epizootic. The death of agricultural poultry was noted in several regions of the European part of Russia and epizootics continued until the end of 2017. This paper presents the data on circulation of highly pathogenic influenza virus over the past two years. The current status regarding H5 influenza in the territory of the Russian Federation is also considered, where for the first time since 2005 a large-scale epizooty caused by the influenza virus subtype A (H5N8) was recorded. It is shown that the territory of Russia plays an important geographical role in the spread of influenza virus by wild birds from Southeast Asia to Europe and North America, and the research also suggests the possible continuation of circulation of highly pathogenic viruses in the territory of Russia