Известно, что белок норовируса VP1 способен самостоятельно собираться в вирусоподобные частицы (ВПЧ), на которые развивается достаточно сильный иммунный ответ. Нами получен рекомбинантный VP1 эпидемического варианта норовируса генотипа GII.4, доминировавшего на территории Нижегородской области в 2018 г. Показана способность VP1 к самосборке, его безопасность и иммуногенность. ВПЧ на основе VP1 норовируса использованы в качестве молекулярной платформы для разработки вакцины против коронавирусной инфекции. Для этого проведена замена части белка VP1, экспонированной на поверхности ВПЧ, на аминокислотную последовательность SARS-CoV-2, кодирующую сайты связывания с рецепторами (RBD). Для увеличения растворимости и корректного фолдинга N-концевая часть рекомбинантной химеры VP1 норовируса с RBD SARS-CoV-2 слита с периплазматическим мальтозосвязывающим белком E.coli с включением сайта для специфичного гидролиза. Проведена оптимизация экспрессии, растворения и очистки слитого белка VP1 норовируса с RBD SARS-CoV-2. Полученная химерная структура может быть использована в составе вакцины для профилактики COVID-19, применимой для интраназальной вакцинации.
Helicobacter pylori is considered the etiological agent of acute and chronic forms of gastritis, and is also capable of exerting a multifactorial effect on the host organism and on the nature of the immune response. The inflammatory response to H. pylori infection has its own characteristics. With an active course, inflammatory reactions, when the modulating effect of regulatory T-lymphocytes (T-reg) is weakened and populations of pro-inflammatory cells (T-helpers 1, 17, 22 type and follicular T-helpers) are activated, which have pronounced destructive changes in the gastric mucosa and the duodenum. guts. Macrophages, dendritic cells and neutrophils are cellular factors of the innate immune system, as well as adaptive immunity, which provides protection against infection. In turn, H. pylori uses a variety of mechanisms to evade the destruction of the host immune system. Long-term preservation of inflammation can cause local activation of mutagenesis, which initiates the development of malignant neoplasms of the gastric mucosa. A review of the host immune response to H. pylori is devoted to this analytical review.
Abstract. Helicobacter pylori is considered an etiological agent of chronic gastritis and a number of other diseases of the gastrointestinal tract. The immune response to H. pylori is characterized by the development of both pro-inflammatory and tolerogenic reactions. Against this background, the possibility of forming autoimmune shifts is also assumed. The purpose of the present work was to conduct a comparative analysis of the state of immunity in patients with chronic gastritis in the exacerbation stage associated with and not associated with H. pylori infection. There were used whole peripheral blood (n=50) and serum (n=49)samples from 162 patients with primary chronic gastritis at the exacerbation stage, in which the presence or absence of H. pylori DNA was tested by real-time PCR in gastric juice.In the peripheral blood of patients, the relative content of CD4+FoxP3+ cells (T regulators) and CD4+CD161+ cells (IL-17 producing cells) was evaluated using flow cytofluorometry and monoclonal antibodies, the level of mRNA FoxP3 and mRNA IL-17A was determined using real time RT-PCR, and the concentration of IL-2 and IL-23 was determined using enzyme immunoassay. It has been shown that in H. pylori-infected patients with chronic gastritis in the exacerbation stage in comparison with patients not infected with H. pylori, the content of CD4+FoxP3+ cells, CD4+CD161+ cells does not change in the blood, with also the level of mRNA FoxP3 and mRNA IL-17A. Since the equilibrium between the populations of Th17 cells and T regulators is modulated by IL-2, which is important for generating the population of T regulators, but inhibits polarization of the immune response towards the Th17 of cells, we conducted a comparative assessment of the serum IL-2 level in patients with chronic gastritis. All patients showed an increase in IL-2 content in comparison with the norm. In this case, the concentration of IL-2 in the blood of infected H. pylori patients was statistically significantly higher than in H. pylori-uninfected patients. An important regulator of the function of Th17 cells is also IL-23, which induces the differentiation of naive T-lymphocytes into Th17 cells involved in inflammatory and autoimmune reactions. In this regard, we determined the level of this cytokine in the blood of patients with chronic gastritis. Multiple increase of IL-23 concentration in comparison with normal level and higher content of IL-23 in H. pylori-infected patients in comparison with uninfected patients were revealed. On the basis of the obtained data, it can be concluded that an increase in the concentration of IL-23 does not exclude the possibility of forming autoimmune shifts with its participation in persons with helicobacter infection, but the issue requires further study.
Helicobacter pylori (H. pylori) increases the risk of diseases associated with mucous membrane inflammation of gastrointestinal tract, in particular, gastritis, stomach ulcers, and duodenal ulcers. It may also induce a chronic immune response, causing damage to the mucous membrane and development of these diseases. In addition, the role of H. pylori in the initiation of a wide range of autoimmune diseases is discussed. The aim of this study was to assess the level of autoantibodies – markers of various autoimmune diseases in the blood of H. pylori-infected patients with chronic gastritis. We used samples of whole peripheral blood from 267 primary patients with chronic gastritis in the acute stage. The presence of H. pylori in gastric juice from patients was determined using real-time PCR. The level of autoantibodies to double-stranded and single-stranded DNA, autoantibodies to thyroglobulin, thyroid peroxidase, concentration of rheumatoid factor, IgG autoantibodies to the cyclic citrullinated peptide, IgM and IgG autoantibodies to beta(2)-glycoprotein were determined by the enzyme immunoassay. The average level of rheumatoid factor in blood serum was similar for H. pylori-infected and non-infected patients, and did not exceed the normal values. The level of antibodies to cyclic citrullinated peptide, one of the sensitive markers of rheumatoid arthritis, was increased in all patients, being, however, significantly lower in H. pylori-infected patients compared with non-infected persons. Autoantibodies to thyroglobulin, thyroid peroxidase are considered classic markers of autoimmune diseases of the thyroid gland. In blood of H. pylori-infected patients we have found an increased concentration of autoantibodies to thyroglobulin and thyroid peroxidase in comparison with non-infected ones, but the average level of these antibodies did not exceed the normal range. Any differences in the levels of systemic lupus erythematosus serological markers, i.e., autoantibodies to double-stranded and single-stranded DNA, were found between H. pylori-infected and non-infected patients. The levels of thrombosis risk marker in patients with systemic lupus erythematosus (IgG and IgM autoantibodies to beta(2)-glycoprotein) were also within the normal ranges. However, in H. pylori-infected patients, it even turned out to be statistically significantly lower than in non-infected ones. Thus, no data have been obtained on increased levels of the tested markers of autoimmune pathology in blood of H. pylori-infected patients with chronic gastritis at the acute stage. However, this does not allow us to make an unambiguous conclusion that the influence of H. pylori does not affect the development of immunological changes associated with autoimmune diseases.
The virologists’ attention to bats (Сhiroptera) changed in the late 20th century as the concept of emerging infections grew in popularity. Since the beginning of the COVID-19 pandemic, the number of publications on bat viruses has increased profoundly.History of the problem; biodiversity of Chiroptera and related viruses; medical and veterinary significance of some viral genera and subgenera (Lyssavirus, Henipavirus, Marburgvirus, Ebolavirus, Sarbecovirus, Merbecovirus), as well as problems of bat protection, are addressed in a concise form. Literature search was carried out in electronic databases, mainly for the period of 2000–2021. Publications in Russian that are poorly represented in English-language reviews are also included. The purpose of the review is to substantiate the importance of an interdisciplinary approach in the context of increased interest in the study of viral infections in bats. This review was written for researchers who have not previously dealt with this problem.Since the beginning of this century, the number of known virus species associated with bats has increased by an order of magnitude (>200). The families Rhabdoviridae, Coronaviridae, Paramyxoviridae are in the first ranks according to the number of findings, and the highest diversity of viruses has been established for the families Vespertilionidae, Pteropodidae, Molossidae. Interdisciplinary cooperation positively influences the efficiency, biological safety and practical significance of the ongoing research. The best results were achieved by multidisciplinary teams with good cross-training in several specialties. Many papers emphasize the need to balance health and conservation interests.The analysis of scientific publications indicates a change in research approaches in this area: from collecting individual facts within the framework of narrow specialties to a comprehensive assessment of new knowledge from ecological, evolutionary and socio-economic positions. Results of the research emphasize the need to maintain complex approaches addressing public health needs and environmental protection. The importance of bat-borne viral infections determines the necessity for correction and interdepartmental coordination of scientific research and surveillance of wildlife zoonoses in the Russian Federation.
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