Influence of the Protective Antigen, Produced by <i>Bacillus anthracis</i> Asporogenic Recombinant Strain, on the Immune System of Laboratory Animals

Assessment of immunogenicity and biological safety of protective antigen preparation obtained from asporogenic recombinant producer, B. anthracis 55ΔTPA-1(Spo-), is made on the mice (BALB/c species) and Guiney pigs models. It is shown that the development of adaptive immunity in the inoculated with purified protein laboratory animals is characterized by high titers of specific antibodies. Double immunization of biological models with antigen preparation confers protection from B. anthracis infection, commensurable with protective capacity of the live anthrax vaccine. Obtained are the data confirming the possibility to reduce the injected doze of the vaccine strain in case of subsequent single immunization with protective antigen. It is determined that recombinant protective antigen shows no sign of reactogenicity and does not damage thymocytes and splenocytes in laboratory animals when administered for immunization

CHARACTERIZATION OF AVIAN INFLUENZA H5N8 VIRUS STRAINS THAT CAUSED THE OUTBREAKS IN THE RUSSIAN FEDERATION IN 2016–2017

Objective of the study is to investigate biological properties of avian influenza virus strains that caused the outbreaks in Russia in 2016–2017.Materials and methods. The study was performed using advanced virological and molecular-biological methods in state-of-the-art equipment.Results and conclusion. In 2016, the outbreaks among wild birds and poultry caused by highly pathogenic avian influenza H5N8 virus have occurred in the territory of the Russian Federation. In May, 2016 an outbreak of H5N8 among wild birds was registered in the territory of the Republic of Tyva. In October-November, 2016 influenza virus H5N8 was isolated in the territory of the Republics of Tatarstan and Kalmykia, Krasnodar and Astrakhan Regions of Russia. In 2017 avian influenza H5N8 has become widespread in European part of Russia and caused multiple outbreaks among wild birds and poultry. Results of the investigations of the isolated strains show that all of them are highly pathogenic and belong to the clade 2.3.4.4. Molecular-genetic and virological analysis has revealed the differences between the viruses isolated in 2016–2017 and the virus of the same clade 2.3.4.4 that was isolated in 2014

Гуманизированные животные как модели экспериментальной онкологии (обзор литературы)

The humanization of immunodeficient animals allows us to study the growth of xenografts of human malignant tumors and their response to therapeutic effects, taking into account processes in the immune system and tumor zone, which have a significant impact on oncogenesis and the effectiveness of antitumor therapy. Such experimental models are currently considered as the most advanced tool in the development of personalized antitumor treatment. The lines of immunodeficient animals most commonly used for the transplantation of mature and stem human immune cells have been characterized. The main sources of human immune cells when implementing the hu-pbl and hu-cd34+ models, as well as the blt model (as an option to the cd34+ model) are described. The basic procedures necessary for reproducing each model, their modification in adult and newborn animals are outlined as well as the parameters of immunosuppressive radiation exposure, preceding the transplantation of human hematopoietic stem cells. The main results of the humanization of immunodeficient animals and examples of the use of these models for the purposes of fundamental and clinical oncology are described. The main problems of this direction are discussed. The review is based on an analysis of the literature presented in the scopus, web of science, medline, risc and others databases over the past 7 years (over 80 % of literature sources, with more than over 50 % of studies published over the last 3 years).Гуманизация иммунодефицитных животных позволяет исследовать рост ксенотрансплантатов злокачественных опухолей человека и их реакцию на лечебные воздействия с учетом процессов в иммунной системе и зоне опухоли, оказывающих значительное влияние на онкогенез и эффективность противоопухолевой терапии. Такие экспериментальные модели в настоящее время рассматриваются в качестве наиболее совершенного инструмента при разработке персонализированного противоопухолевого лечения. В обзоре охарактеризованы линии иммунодефицитных животных, используемых для трансплантации зрелых и стволовых клеток иммунной системы человека, описаны основные источники получения иммунных клеток человека при реализации Hu-pBl и Hu-cd34+ моделей, обозначены основные процедуры, необходимые для воспроизведения каждой модели, их модификации у взрослых и новорожденных животных, а также параметры иммуносупрессивного лучевого воздействия, предваряющего трансплантацию гемопоэтических стволовых клеток человека. Описаны основные результаты гуманизации иммунодефицитных животных и примеры использования этих моделей для целей фундаментальной и клинической онкологии. Обсуждаются основные проблемы данного направления. Обзор составлен на основе анализа литературы, представленной в базах данных scopus, Web of science, medline, РИНЦ и др. за последние 7 лет (более 80 % источников, при этом более 50 % работ были опубликованы за последние 3 года)

Paradoxical Effects of Rapamycin on Experimental House Dust Mite-Induced Asthma

The mammalian target of rapamycin (mTOR) modulates immune responses and cellular proliferation. The objective of this study was to assess whether inhibition of mTOR with rapamycin modifies disease severity in two experimental murine models of house dust mite (HDM)-induced asthma. In an induction model, rapamycin was administered to BALB/c mice coincident with nasal HDM challenges for 3 weeks. In a treatment model, nasal HDM challenges were performed for 6 weeks and rapamycin treatment was administered during weeks 4 through 6. In the induction model, rapamycin significantly attenuated airway inflammation, airway hyperreactivity (AHR) and goblet cell hyperplasia. In contrast, treatment of established HDM-induced asthma with rapamycin exacerbated AHR and airway inflammation, whereas goblet cell hyperplasia was not modified. Phosphorylation of the S6 ribosomal protein, which is downstream of mTORC1, was increased after 3 weeks, but not 6 weeks of HDM-challenge. Rapamycin reduced S6 phosphorylation in HDM-challenged mice in both the induction and treatment models. Thus, the paradoxical effects of rapamycin on asthma severity paralleled the activation of mTOR signaling. Lastly, mediastinal lymph node re-stimulation experiments showed that treatment of rapamycin-naive T cells with ex vivo rapamycin decreased antigen-specific Th2 cytokine production, whereas prior exposure to in vivo rapamycin rendered T cells refractory to the suppressive effects of ex vivo rapamycin. We conclude that rapamycin had paradoxical effects on the pathogenesis of experimental HDM-induced asthma. Thus, consistent with the context-dependent effects of rapamycin on inflammation, the timing of mTOR inhibition may be an important determinant of efficacy and toxicity in HDM-induced asthma

АВАРИЯ НА АЭС «ФУКУСИМА-1»: ПЕРВЫЕ ИТОГИ АВАРИЙНОГО РЕАГИРОВАНИЯ. СООБЩЕНИЕ 2: ДЕЙСТВИЯ ОРГАНОВ РОСПОТРЕБНАДЗОРА ПО РАДИАЦИОННОЙ ЗАЩИТЕ НАСЕЛЕНИЯ РОССИЙСКОЙ ФЕДЕРАЦИИ НА РАННЕЙ СТАДИИ АВАРИИ

Basic measures of the Rospotrebnadzor emergency response during the early stage of the «Fukushima-I» NPP radiation accident are being analyzed in the article. Radiation monitoring of the environmental objects of the territories of the Russian Federation Far East Federal District, radiation control of arriving from Japan vehicles, freights and passengers as well as imported from Japan food products were promptly organized. This allowed to get reliable evaluations of the levels of radioactive contamination at the Russian Federation territory and population exposure doses due to the «Fukushima-I» NPP accident, timely exclude the possibility of import to the Russian territory for the freights, vehicles, food products having contamination exceeding established in the Russian Federation standards.В статье проанализированы основные мероприятия по аварийному реагированию Роспотребнадзора в ранней стадии развития радиационной аварии на АЭС «Фукусима-1». Оперативно организован ради- ационный мониторинг объектов окружающей среды на территории субъектов Российской Федерации Дальневосточного Федерального округа, входной радиационный контроль транспортных средств, грузов и пассажиров, прибывающих из Японии, а также импортируемых из Японии пищевых продуктов. Это позволило получить достоверные оценки уровней радиоактивного загрязнения территории России и доз облучения населения вследствие аварии на АЭС «Фукусима-1», своевременно исключить возможность ввоза на территорию России грузов, транспортных средств, пищевых продуктов, имеющих радиоак- тивное загрязнение свыше установленных в Российской Федерации нормативов