There are no effective approaches to treatment and prevention of many infectious diseases representing a significant danger to humans. So far, mass vaccine immunization is among the most efficient and widely used approaches to prevent outbreaks of viral and bacterial infections. Mass immunization helps to reduce the number of carriers of infections, thus significantly decreasing probability of infection dissemination. Recent promising developments include genetically engineered vaccines based on adenoviral vectors, many of which are already at various stages of clinical trials. Genetic immunization with recombinant adenovirus-based vaccines allows delivery of the genes encoding only required antigens to human cells, thus allowing avoidance of conventional vaccines, e.g., live pathogenic viruses and bacteria, and providing versatile technologies for vaccine development. These advances significantly reduce the time needed for vaccine production and, respectively, the development and creation of new vaccines, thus being an important factor in decreasing risk of epidemics and pandemics. Advantages of adenoviral vectors include high ability of penetration into human cells, a potential for induction of both humoral and cellular immune response, rather long and active production of antigens following administration of adenoviral vectors into the human, safe usage, ease of obtaining preparative quantities of vaccines. In this review, we provide information about the ongoing worldwide clinical trials of adenoviral vector-based vaccines against various infectious diseases, like as to consider selection parameters of volunteers participating in the testing, vaccination schedule, doses and methods of drug administration, results of completed experiments, and preliminary data on currently ongoing research.

Over last decade, a substantial progress has been made, with respect to understanding of cancer biology and its interplay with the host immune system. Different immunotherapeutic drugs based on recombinant cytokines and monoclonal antibodies are widely used in cancer therapy, and a large number of experimental cancer treatments have been developed, many of which are currently undergoing various stages of clinical trials. Recent endorsement of a recombinant oncolytic herpesvirus T-VEC for the treatment of melanoma was an important step towards a more safe and efficient anticancer therapeutics. In this review, we shall mention only some of the most promising cancer immunotherapy strategies, namely, immune checkpoint inhibitors, cellular therapy and oncolytic viruses.

 

Conventional strategies for cancer treatment are close to their efficiency limits. Meanwhile, rapid development of experimental immunology and immunotherapy led to first successful experiences in antitumor vaccination. Over last decade, remarkable results were obtained by means of anticancer vaccination being implemented into clinical settings thus causing popularity and growth of interest to tumor-specific DNA vaccines. In this review, we discuss basic principles of a DNA vaccine construction, their structural characteristics and diversity, mechanisms of their biological action, pharmaceutical forms and delivery routes into the body.

 

So far, there is no effective treatment for a number of socially significant bacterial and fungal diseases. β-(1→3) glucans are polysaccharides consisting of glucose units linked together with β-(1→3)- glycoside bonds. They are principal components of the fungal cell wall including such dangerous nosocomial pathogens as Candida albicans, Aspergillus fumigatus and others. At the same time, β-(1→3) glucans are absent in humans and other mammals, thus making them to be promising components of carbohydrate-protein conjugate vaccines for prevention and treatment of fungal infections. The CRM197 protein is a non-toxic derivative of diphtheria toxin, which is widely used as a safe carrier for conjugate vaccines. The CRM197 extraction from lysogenic C. diphtheriae cultures is a classic way of its production. An alternative to the classic method is a transgene-driven CRM197 protein expression in E. coli, B. subtilis and Pseudomonas fluorescens. The advantage for using Escherichia coli in this case is that this method is more simple and inexpensive, and allows of producing recombinant CRM197 within short terms employing a non-pathogenic microorganism. The purpose of this study was to investigate antigenic activity in the samples of experimental conjugate vaccines based on synthetic oligosaccharide ligands and CRM197 carrier protein, by means of a competitive ELISA. A double immunization of laboratory Balb/c mice with experimental samples of conjugate vaccines based on oligosaccharide ligands and CRM197 protein caused induction of specific antibodies at high titers. All the samples of oligoglucoside-based conjugate vaccines with different contents of monomeric units (pentasaccharides, heptasaccharides, nanosaccharides, and undecasaccharides) caused the formation high antibody titer at the level 1: 51,200,following tandem injections. High avidity of antibodies to their oligosaccharide ligands was shown by competitive ELISA reaction. These data suggest a relevance of further pre-clinical trials of conjugate vaccines against Candida and Aspergillus, as well as selection of the most immunogenic and effective version of the conjugate vaccine.

 

Sixteen female patients with diabetes-associated osteoarthritis (DAOA) participated in an openlabel, randomized, cross-over study. The mean patients’ age was 65.5 (±5.4) years, the patients were obese (mean body mass index, 35.8±5.7 kg/m2 ). They suffered from durable osteoarthritis (14.5±7.6 years) associated with diabetes mellitus (13.08±3.43 years). Clinical and radiographic signs of knee OA were observed in 100% of the cases, all the patients had Kellgren–Lawrence grade III radiographic changes. First group of patients (n = 9) was randomized to Fenofibrate (145 mg/day for 12 weeks), the second group (n = 7) received chondroitine sulfate (1000 mg/day for 12 weeks). Then, following a two-week washout period, the first group was switched to chondroitine sulfate and the second group, to fenofibrate. Clinical examination was performed monthly, and laboratory evaluation was performed at the baseline and by the end of each treatment course. pain level according to VAS scale was used as the primary endpoint, whereas KOOS, WOMAC, ICOAP and other scores served as secondary endpoints. We have also assessed effects of Fenofibrate upon serum biomarkers (IL-6, IL-18, IL-10, lipid profiles, and CRP concentrations). Comparative effect of Fenofibrate was evaluated by means of generalized estimating equation (GEE) models adjusted for the treatment sequence. It was shown that clinical effects of Fenofibrate in patients with DAOA did not significantly differ from those of chondroitine sulfate. However, fenofibrate had broader spectrum of effects including improvement of lipid profiles. E.g., Fenofibrate treatment was associated with increased HDL levels (β coefficient, -0.19; р = 0.02), a decrease in total cholesterol (β coefficient, -0.78; р = 0.01), and triglycerides (β coefficient,0.85; р = 0.002). In addition, Fenofibrate therapy was associated with a decrease in ESR, a laboratory biomarker of systemic inflammation (β coefficient, -7.76; р = 0.01). Cytokine changes following the Fenofibrate treatment did not differ from those registered after chondroitine sulfate therapy. In conclusion, the results of this pilot study provide a rationale for further studies of PPARα agonists and their pleiotropic effects in large-scale controlled clinical trials.

 

Distinct changes of B-cell subpopulations are observed in most systemic rheumatic diseases associated with polyclonal B cell hyperreactivity. Immunosuppressive and cytostatic therapy may also differentially influence B lymphocyte subsets in these. We studied subpopulations of B cells in systemic rheumatic patients along treatment with cytostatics. We analyzed B cell phenotypes in ninety-nine blood samples from the patients with systemic lupus erythematosus (SLE, n = 25), systemic sclerosis (n = 27), Sjogren’s syndrome (n = 47) in the course of their hospital treatment. Control group consisted of 49 healthy blood donors. Phenotyping of blood B-cell subpopulations was performed by means of flow cytometry (Beckman Coulter, USA). Naïve B-cell subpopulations in SLE patients who underwent cyclophosphan treatment, were underrepresented, if compared with normal control group, whereas plasmablast levels were increased irrespectively of medication mode. B cell population exhibits a natural heterogeneity, thus making it necessary to analyze distinct B cell subpopulations as independent functional units, when studying different rheumatic diseases. The levels of plasmablasts which are active antibody producers, remain high, despite immunosuppressive therapy performed in SLE. Thus, therapy targeted against certain B cell subsets, could be able to provide a more effective treatment for the patients with systemic rheumatic diseases.

Search for molecular genetic markers of risk and prognosis of breast cancer is an important prospective of modern research. Many molecular mechanisms are involved in pathogenesis of breast cancer and define a wide range of possible candidate genes. The genes of pro-inflammatory cytokine receptors, such as tumor necrosis factor and interleukin-1, are also among potential candidate genes. Numerous functional allelic variants of these genes have been shown which are associated with changed expression of membranebound and soluble forms of the receptors. In addition, they are expressed both on immunе cells and epithelial and endothelial cells. They regulate functional status of the cells, synthesis and activities of enzymes controlling extracellular matrix and angiogenesis factors. These functions of tumor necrosis factor and interleukin-1 receptor proteins may contribute to pathogenesis of tumor growth. The aim of present study was to compare frequency of functional allelic variants of genes encoding TNF and IL-1 receptors in breast cancer patients and healthy women. We performed genotyping of distinct SNPs (rs4149569 TNFRSF1A, rs590368 TNFRSF1B, rs2234650 IL1RI, and rs4141134 IL1R2) that previously were shown to be associated with expression of TNF and IL-1 receptors on immune cells. Comparative analysis of the genotype frequencies in the samples under study showed a significantly reduced frequency of CC homozygotes for rs590368 polymorphism (TNFRSF1B gene), and increased ratio of CT heterozygotes for rs2234650 polymorphism (IL1R1 gene) among breast cancer patients. Hence, some gene polymorphisms associated with altered expression levels of TNF and IL-1 receptors on immune cells may represent a factor which may determine involvement of proinflammatory cytokines into pathogenesis of breast cancer.

 

Introduction: Mechanisms of immune response in COPD are still poorly understood, despite global challenge which this disorder presents to public medicine. The objective of this study was to evaluate IL-6R expression on the surface of immune cells in the course of COPD progression. Materials and methods. The study included 112 patients with stable mild, moderate and severe COPD (spirometry classes 1,2, and 3). A control group included 32 healthy subjects. The COPD patients were in remission phase. Expression of IL-6R on the surface of T lymphocytes, T helper cells, monocytes and granulocytes was determined by flow cytometry. Results and Discussion. Progression of the disease was accompanied by increase in the relative amounts of CD126+ immunocompetent cells. The number of CD4+CD126+ cells was maximally increased at all stages of COPD. Moreover, the number of CD126+ granulocytes proved to be significantly increased with increasing severity of COPD. Hence, it may be assumed that T-helper cells and granulocytes are primary target cells for IL-6 anti-inflammatory action, which is mediated by classic signaling.

At present time, there is an obvious need for a new generation of vaccines as the most effective preventive approach, in order to stop spreading of tuberculosis infection. So far, the most popular strategy is aimed at heterological vaccination. The idea is to use BCG, or improved BCG, or attenuated M. tuberculosis for primary vaccination. For the further booster vaccination one may apply thw s.c. subunit or vector vaccines, containing protective mycobacterial proteins. The aim of our investigation was to evaluate protective effects of a new vaccine based on recombinant bacterial proteins Ag85, ТВ10 and FliC. We used a model with aerosol M. tuberculosis H37Rv infection, and compared lung and spleen CFU counts and life-span of vaccinated versus non-vaccinated С57BL/6 mice. As a result, we revealed three vaccine variants with comparable protective capacity against BCG using our experimental model. The most promising variant is suggested for testing in preclinical trials.