Vol 64, No 1 (2019)
- Year: 2019
- Articles: 7
- URL: https://journal-vniispk.ru/0507-4088/issue/view/6145
- DOI: https://doi.org/10.36233/0507-4088-2018-64-1
Full Issue
REVIEWS
ADJUVANTS OF INFLUENZA VACCINES: NEW POSSIBILITIES OF USING SULPHATED POLYSACCHARIDES FROM MARINE BROWN ALGAE
Abstract
The review article presents the characteristics of the main adjuvant groups (mineral salts of aluminum, synthetic squalene-based adjuvants - MF59 and AS03, CpG-oligodeoxynucleotides, virosomes, polyoxidonium, sovidone) included in the licensed influenza vaccine. The main mechanisms of adjuvant action, advantages and disadvantages of these adjuvants are shown. The vaccines adjuvants in the phase of experimental studies and clinical trials (ISCOMs, Advax™, chitosan) are described too. Particular attention is paid to sulfated polysaccharides (fucoidans) from marine brown algae as vaccine adjuvants. Numerous results of their application in compositions of experimental vaccines are presented. The prospects of sulfated polysaccharides using in the design of influenza vaccines are estimated. These prospects are determined by high biocompatibility, low toxicity and good tolerance of the human body to fucoidans, as well as mechanisms of their adjuvant activity. Sulfated polysaccharides are agonists of toll-like receptors of innate immunity cells and powerful inducers of the cellular and humoral immune response, which is important for the development of influenza vaccines. The review is based on the information presented in the bibliographic and abstract databases of scientific publications, search engines and publishers: RSCI, Web of Science, Scopus, MEDLINE, Google Scholar, PubMed, Springer Nature, Elsevier and others.
Problems of Virology. 2019;64(1):5-11
5-11
ANTIHIV/AIDS DRUG 6HP: ANTIVIRAL ACTIVITY, PRE-CLINICAL STUDY. EFFICIENCY IN ADULT HIV-INFECTED PATIENTS
Abstract
The new domestic antiretroviral drug 6HP, which is ammonium-3’-azido-3’-deoxythymidine-5’-carbomoylphosphonate, shows a high level of anti-HIV activity in cultures of lymphoblastoid cells. In a organism, the 6HP is converted to azidothymidine, and the its pharmacokinetic parameters indicate a prolonged nature of action of this compound in vivo. It is an important indicator that allows to formulate optimal therapeutic regimens during clinical application of 6HP. The complex of its antiviral properties and the results of its exhaustive preclinica study, as well as the results of studying its safety and tolerability in adult HIV-infected patients, including important first data of its use as a specific therapeutic anti-HIV / AIDS drug, certainly indicate on its prospects and its usefulness in clinical use in patients with HIV infection, including as part of combination antiretroviral therapy.
Problems of Virology. 2019;64(1):12-15
12-15
ORIGINAL RESEARCH
EVALUATION OF THE MOLECULAR-BIOLOGICAL PROPERTIES OF HUMAN ROTAVIRUS A STRAIN WA
Abstract
Introduction. Rоtaviruses are amоng the leading causes of severe diarrhea in children all over the Wоrld. Vaccination is considered to be the mоst effective way to cоntrоl the disease. Currently available vaccines for prevention of rоtavirus infection are based on live attenuated rotavirus strains human оr animal origin. Objectives and purposes. The aim of this investigation was to study the biological and genetic properties of an actual epidemic human rotavirus A (RVA) strain Wa G1P[8] genotype. Material and methods. RVA Wa reproduction in a monolayer continuous cell lines, purification and concentration of RVA antigen, PAAG electrophoresis and Western-Blot, electrophoresis of viral genomic RNA segments, sequencing. Results. Human RVA G1P[8] Wa strain biological and molecular genetic properties were assessed in the process of the adaptation to MARC145 continuous cell line. Cell cultured RVA antigen was purified, concentrated and then characterized by the method of PAAG electrophoresis and immunoblot. To verify RVA Wa genome identity, electrophoresis of viral genomic RNA segments was performed. The lack of accumulation of changes in the RVA Wa genome during adaptation to various cell cultures and during serial passages was demonstrated by sequencing fragments of the viral genome. Conclusion. RVA Wa strain is stable, it possesses high biological activity: it has been successfully adapted to the MARC145 cell line and RVA Wa virus titer after the adaptation reached 7,5-7,7 lg TCID50/ml. The identity of the cultivated RVA to the original strain Wa G1P[8] was confirmed.
Problems of Virology. 2019;64(1):16-22
16-22
INFLUENCE OF INGARON ON THE DYNAMICS OF INTERFERON-α AND -γ PRODUCTION AND ON THE MANIFESTATION OF CLINICAL SYMPTOMS IN PATIENTS WITH CHRONIC VIRUS EРSTHTEIN-BARR INFECTION
Abstract
Introduction. Patients with chronic herpes virus infection develop impaired IFN-α and IFN-γ products due to secondary immunodeficiency, which leads to impaired elimination of the intracellular virus and the development of chronic recurrent infection. It has been shown that IFN-γ is a potent immunoregulatory cytokine and has an antiviral effect. The aim of the study is to study the effect of Ingaron therapy on the dynamics of IFN-α and IFN-γ production and the clinical picture in patients with chronic Epstein-Barr virus infection (ChEBVI). Material and methods. 32 patients with ChEBVI were examined. The average age of patients was 35.06 ± 1.60 years. There were 22 women, 10 men. Serum IFN-α and IFN-γ, spontaneous and induced cytokine production in blood lymphocyte cultures were determined. As an inducer of IFN-α products, the Newcastle disease virus was used (obtained in the LA Tarasevich State Medical Institute, St. Petersburg) with an infectious titer of 8 lg EID / 0.2 ml in a volume of 8 μl per well, as an inducer of IFN-γ products, phytohemagglutinin (PanEco, Russia) was used at a dose of 10 µg / ml. The quantitative content of cytokines was determined in the serum and supernatant of a 24-hour whole blood culture using enzyme-linked immunosorbent assay (ELISA) using test systems (Vector Best, Russia). Results. It was shown that the content of IFN-γ decreased (P = 0.013) after Ingaron therapy in patients with initially high levels of induced IFN-γ (4435.64 ± 1343.50 pg/ml). In patients with initially low levels of induced IFN-γ (234.25 ± 34 , 31 pg / ml) the content of IFN-γ increased (P = 0.002). Ingaron leads to an increase in spontaneous and serum IFN-γ production in patients. Conclusions. Conducting Ingaron therapy with ChEBVI is shown independently of the initial production of IFN-γ-induced lymphocyte culture. Ingaron is recommended for the treatment of patients with ChEBVI at a dose of 500,000 IU with a course dose of 10 or more injections.
Problems of Virology. 2019;64(1):23-29
23-29
LOW CONCENTRATIONS OF HEPATITIS C VIRUS RNA IN SEROLOGICALLY MILD INFECTION
Abstract
Occult HCV infection (OCI) provides significant interest recently. HCV RNA in this case can be detected not in plasma, but in blood cells and/or in liver tissue. In case of antibody genesis impairment anti-HCV detection may lead to negative or “uncertain” result. The aim of the study was to estimate infection type in blood donors and patients with hematological diseases by exploration of samples with uncertain anti-HCV detection results. Blood samples of 30 180 potential blood donors’ and 4322 patients with hematological diseases were tested. Comparative analysis of wide pattern of HCV markers was performed. 33 blood donors and 42 patients were enrolled in follow-up examination. Uncertain results of Anti-HCV detection in donors’ samples were in 0.18% of cases. Follow-up examination of 33 donors provided discordant results using immunochemiluminescence assay and ELISA. 15.2% donors’ samples contained HCV RNA in low concentration. Follow-up observation of 42 patients with incomplete antiviral antibody pattern showed HCV RNA presence in 40.5% cases (21.4% high viremia and 19.0% low viremia). Samples with low RNA concentration contained low titers of anti-core antibodies. Samples with high titers of anti-core antibodies contained high HCV RNA level. Uncertain results of anti-HCV in 15.2% of potential blood donors’ samples were confirmed by detection of HCV RNA in low concentration. It proved OCI presence in these individuals and called for testing for wide pattern of HCV markers in addition to routine screening. Patients with hematological diseases showed low level of HCV RNA along with low titers of antibodies against one or two viral antigens.
Problems of Virology. 2019;64(1):30-35
30-35
HEMORRHAGIC FEVER WITH RENAL SYNDROME GROUP OUTBREAK CAUSED BY SOCHI VIRUS
Abstract
Introduction. Hemorrhagic fever with renal syndrome (HFRS) occupies a leading place among natural focal human diseases in the Russian Federation. Sporadic incidence of HFRS-Sochi has been annually recorded in the Krasnodar Territory since 2000. The group outbreak of the HFRS-Sochi was first registered in Gelendzhik in the fall of 2013. Material and methods. Serological methods were used: indirect immunofluorescence, enzyme immunoassay, FRNT in Vero cells, and methods for the viral RNA detection: PCR and RT-PCR. Results. Data of clinical, epidemiological, immunological and molecular studies of 3 out of 4 cases in HFRS-Sochi outbreak are presented. Severity of the disease correlated with early gastrointestinal disorders appearance. Patient MA gastrointestinal disorders were joined on day 3 of a fever. Clinical and laboratory studies revealed signs of kidneys, liver, pancreas damage, bilateral hydrothorax, bilateral polysegmental pneumonia and polyneuropathy. As a result of long-term treatment, the patient recovered. Patient AA had gastrointestinal disturbances the next day after fever onset. The patient was not saved, despite early hospitalization. Hantavirus antigen and RNA were detected in the lung tissues 2 out of 10 Black-Sea field mice captured in the affected area, as well as in the organs of deceased patient. Discussion. The most severe clinical course of the disease in close relatives, son and father, with a fatal outcome in the latter case may be the result of genetic features. The severity and outcome of the disease was not depend on day of hospitalization and correlated with the early manifestations of gastrointestinal disorders. Conclusion. Presented data confirm high virulence and pantropism of the Sochi virus, as well as the epidemiological role of Black-Sea field mouse (Apodemus ponticus) as the host of the Sochi virus and the source of human infection.
Problems of Virology. 2019;64(1):36-41
36-41
DISCUSSION
СASES OF HUMAN CONVALESCENCE FROM RABIES AND LIFETIME DIAGNOSTICS OF LYSSAVIRUS ENCEPHALITIS
Abstract
Notwithstanding the availability of effective vaccines, 40 - 60 thousand rabies cases in humans are reported every year. Almost always the disease is fatal because therapeutic treatment of lyssavirus encephalitis has not been developed. Since 1970 the number of reports on rare cases of convalescence including those using experimental treatment protocols has been gradually increasing 20 cases of convalescence, “partial” convalescence or long-term survival of humans (1970-2015) were selected as they were complaint with laboratory criteria of active lyssavirus infection. Children and teenagers were predominant in the analyzed group (85%). The cases were irregularly spread between the continents: Asia - 6 cases, North America - 6 cases, Africa - 2 cases and Europe - 1 case. India and the USA were on the top of the list of countries by the number of described cases. More than 60% humans were infected from dogs, three cases got infection from bats and 2 cases were allegedly associated with an unknown lyssavirus and an unidentified infection source. 70% cases were vaccinated and 10% cases were treated with gamma globulin before the disease onset. Serological tests for detection of antibodies to lyssaviruses in cerebrospinal fluid of infected humans were typically used for diagnostic laboratory verification. Less than 30% IFA and PCR positives were obtained. Lyssaviruses were never detected. Only 4 convalescent patients were treated using experimental protocols. 80% cases demonstrated severe neurological consequences, four (may be more) patients died afterwards within the period from two months to four years. Different perspectives on prospects of Milwaukee protocol use and other therapeutic techniques are given.
Problems of Virology. 2019;64(1):42-48
42-48