РЕАКТОРНЫЕ И ПОСЛЕРЕАКТОРНЫЕ ИСПЫТАНИЯ И ИССЛЕДОВАНИЯ НА БЫСТРЫХ КРИТИЧЕСКИХ СБОРКАХ ВЫСОКОПЛОТНОГО НИЗКООБОГАЩЕННОГО УРАН-ЦИРКОНИЕВОГО КАРБОНИТРИДНОГО ТОПЛИВА

UZrCN fuel is a high-density, high-temperature fuel that has potential for application in different type reactors. In the past, reactor tests using UZrCN HEU (96% U-235) fuel have been performed to low burnup. However, reactor-testing data are still needed at high burnup to confirm the optimal performance of this-type fuel. The SM-3 research reactor, which is a high-flux reactor located at the State Scientific Center – Research Institute of Atomic Reactors, Dimitrovgrad, Russia, will be used to test a UZrCN LEU (19.73% U-235) fuel to ~40% of burnup. The fuel will then be examined to determine its performance during irradiation.On the “Giacint” and “Kristal” critical facilities located at the Joint Institute for Power and Nuclear Research – SOSNY of the National Academy of Sciences of Belarus, Minsk, Belarus, criticality experiments on multiplying systems modeling physical features of cores with UZrCN LEU (19.75% U-235) fuel have been prepared for use in works on fast reactors with gaseous and liquid-metal coolants. Critical assemblies represent uniform hexagonal lattices of fuel assemblies, each of which consists of 7 fuel rods and has no clad. The active fuel length is 500 mm. Clad material is stainless steel or Nb. Three types of fuel assemblies with different matrix material (air, aluminum and lead) are investigated. These are side radial, top and bottom reflectors – beryllium (internal layer) and stainless steel (external layer).This article desribes the design of the experiment that will be performed in the SM-3 reactor and discusses the results of different calculations that have been performed to show that the experiment design will meet all objectives. The description of construction and composition of critical assemblies with UZrCN fuel and the calculation results are also presented. Топливо UZrCN представляет собой высокоплотное высокотемпературное топливо, которое может применяться в реакторах различных типов. В прошлом реакторные испытания ВОУ (96% U-235) UzrCN-топлива были выполнены только с низким выгоранием. Вместе с тем данные реакторных испытаний необходимы при высоком выгорании для подтверждения оптимальных характеристик этого типа топлива. Высокопоточный исследовательский реактор СМ-3, расположенный в Государственном научном центре – Научно-исследовательский институт атомных реакторов (г. Димитровград, Россия), будет использоваться для испытания НОУ (19,73% U-235) UzrCN-топлива до ~40 % выгорания. Затем топливо будет исследоваться для определения его характеристик после облучения.На критических стендах «Гиацинт» и «Кристал» в Объединенном институте энергетических и ядерных исследований – Сосны Национальной академии наук Беларуси (г. Минск, Беларусь) осуществляется подготовка к экспериментам по критичности на размножающих системах, моделирующих физические особенности активных зон с НОУ (19,75% U-235) UzrCN-топливом для использования в работах по новому поколению быстрых реакторов с газообразными и жидкометаллическими теплоносителями. Критические сборки представляют собой однородные гексагональные решетки топливных сборок, каждая из которых состоит из семи топливных стержней и не имеет оболочки. Длина активной части топливного стержня составляет 500 мм. Материал оболочки – нержавеющая сталь или ниобий. Будут исследованы три типа топливных сборок с различным материалом матрицы в них (воздух, алюминий и свинец). Боковой радиальный, верхние и нижние отражатели – бериллий (внутренний слой) и нержавеющая сталь (внешний слой).В настоящей статье описываются проектные данные эксперимента, который будет осуществлен на реакторе СМ-3, и обсуждаются результаты расчетов, призванные показать, что эксперимент будет отвечать всем поставленным целям. Также представлены описания конструкции и состава критических сборок с топливом UZrCN и результаты их расчетов.

Safety and immunogenicity of rAd26 and rAd5 vector-based heterologous prime-boost COVID-19 vaccine against SARS-CoV-2 in healthy adolescents: an open-label, non-randomized, multicenter, phase 1/2, dose-escalation study

To protect young individuals against SARS-CoV-2 infection, we conducted an open-label, prospective, non-randomised dose-escalation Phase 1/2 clinical trial to evaluate the immunogenicity and safety of the prime-boost “Sputnik V” vaccine administered at 1/10 and 1/5 doses to adolescents aged 12–17 years. The study began with the vaccination of the older cohort (15-to-17-year-old participants) with the lower (1/10) dose of vaccine and then expanded to the whole group (12-to-17-year-old participants). Next, 1/5 dose was used according to the same scheme. Both doses were well tolerated by all age groups. No serious or severe adverse events were detected. Most of the solicited adverse reactions were mild. No significant differences in total frequencies of adverse events were registered between low and high doses in age-pooled groups (69.6% versus 66.7%). In contrast, the 1/5 dose induced significantly higher humoral and T cell-mediated immune responses than the 1/10 dose. The 1/5 vaccine dose elicited higher antigen-binding (both S and RBD-specific) as well as virus-neutralising antibody titres at the maximum of response (day 42), also resulting in a statistically significant difference at a distanced timepoint (day 180) compared to the 1/10 vaccine dose. Higher dose resulted in increased cross-neutralization of Delta and Omicron variants.;Clinical Trial RegistrationClinicalTrials.gov, NCT04954092, LP-007632

Adjuvantation of an influenza hemagglutinin antigen with tlr4 and nod2 agonists encapsulated in poly(D,l-lactide-co-glycolide) nanoparticles enhances immunogenicity and protection against lethal influenza virus infection in mice

Along with their excellent safety profiles, subunit vaccines are typically characterized by much weaker immunogenicity and protection efficacy compared to whole-pathogen vaccines. Here, we present an approach aimed at bridging this disadvantage that is based on synergistic collaboration between pattern-recognition receptors (PRRs) belonging to different families. We prepared a model subunit vaccine formulation using an influenza hemagglutinin antigen incorporated into poly-(D,L-lactic-co-glycolic acid) (PLGA) nanoparticles adjuvanted with monophosphoryl lipid A (TLR4 agonist) and muramyl dipeptide (NOD2 agonist). The efficacy studies were conducted in comparison to control vaccine formulations containing individual PRR agonists. We show that the complex adjuvant based on TLR4 and NOD2 agonists potentiates proinflammatory cell responses (measured by activity of transcription factors and cytokine production both in vitro and in vivo) and enhances the phagocytosis of vaccine particles up to comparable levels of influenza virus uptake. Finally, mice immunized with vaccine nanoparticles containing both PRR agonists exhibited enhanced humoral (IgG, hemagglutination-inhibition antibody titers) and cellular (percentage of proliferating CD4+ T-cells, production of IFNɣ) immunity, leading to increased resistance to lethal influenza challenge. These results support the idea that complex adjuvants stimulating different PRRs may present a better alternative to individual PAMP-based adjuvants and could further narrow the gap between the efficacy of subunit versus whole-pathogen vaccines. © 2020 by the authors. Licensee MDPI, Basel, Switzerland

THE CYTOKINE PROFILE OF MICE DENDRITIC CELLS UNDER THE INFLUENCE OF OprF AND aTox PROTEINS OF PSEUDOMONAS AERUGINOSA

Aim. To study the effect of OprF and aTox proteins of Pseudomonas aeruginosa on the cytokine profile of mice dendritic cells. Materials and methods. Dendritic cells (DC) were obtained from bone marrow cells of BALB/c mice when cultured with 20 ng/ml of recombinant GM-CSF and IL-4 (Biosource, USA). OprF and aTox of P. aeruginosa were used as the inducer of maturation of DC. The level of cytokines was determined in supernatants of DC using the Bio-Plex Pro™ Mouse Cytokine 23-plex Assay (BioRad, USA). Results. Evaluation of the profile and level of cytokines produced by dendritic cells of mice demonstrates the high activity of mature DC. Under the influence of recombinant proteins OprF+aTox, both large amounts of Th-1 cytokines were synthesized: IL-1a, IL-1P, IL-6, TNF-a, Th-2 cytokines: IL- 4, IL-10, IL-13, regulatory cytokines: IL-12, IFN-y, IL-17A and chemokines: KC (CXCL1), MIP-1a (CCL3), MIP-1e (CCL4), RANTES (CCL5). In our studies, we demonstrated the possibility of obtaining mature dendritic cells from the bone marrow of mice under the influence of a complex of P. aeruginosa antigens. Conclusion. The candidate Pseudomonas aeruginosa vaccine based on its recombinant proteins OprF and aTox induces the production of chemokines and Th-1, Th-2, Th-17 cytokines by mice dendritic cells

Chlamydial Type III Secretion System Needle Protein Induces Protective Immunity against Chlamydia muridarum Intravaginal Infection

Chlamydia trachomatis imposes serious health problems and causes infertility. Because of asymptomatic onset, it often escapes antibiotic treatment. Therefore, vaccines offer a better option for the prevention of unwanted inflammatory sequelae. The existence of serologically distinct serovars of C. trachomatis suggests that a vaccine will need to provide protection against multiple serovars. Chlamydia spp. use a highly conserved type III secretion system (T3SS) composed of structural and effector proteins which is an essential virulence factor. In this study, we expressed the T3SS needle protein of Chlamydia muridarum, TC_0037, an ortholog of C. trachomatis CdsF, in a replication-defective adenoviral vector (AdTC_0037) and evaluated its protective efficacy in an intravaginal Chlamydia muridarum model. For better immune responses, we employed a heterologous prime-boost immunization protocol in which mice were intranasally primed with AdTC_0037 and subcutaneously boosted with recombinant TC_0037 and Toll-like receptor 4 agonist monophosphoryl lipid A mixed in a squalene nanoscale emulsion. We found that immunization with TC_0037 antigen induced specific humoral and T cell responses, decreased Chlamydia loads in the genital tract, and abrogated pathology of upper genital organs. Together, our results suggest that TC_0037, a highly conserved chlamydial T3SS protein, is a good candidate for inclusion in a Chlamydia vaccine

Chlamydial Type III Secretion System Needle Protein Induces Protective Immunity against Chlamydia muridarum Intravaginal Infection

Chlamydia trachomatis imposes serious health problems and causes infertility. Because of asymptomatic onset, it often escapes antibiotic treatment. Therefore, vaccines offer a better option for the prevention of unwanted inflammatory sequelae. The existence of serologically distinct serovars of C. trachomatis suggests that a vaccine will need to provide protection against multiple serovars. Chlamydia spp. use a highly conserved type III secretion system (T3SS) composed of structural and effector proteins which is an essential virulence factor. In this study, we expressed the T3SS needle protein of Chlamydia muridarum, TC_0037, an ortholog of C. trachomatis CdsF, in a replication-defective adenoviral vector (AdTC_0037) and evaluated its protective efficacy in an intravaginal Chlamydia muridarum model. For better immune responses, we employed a heterologous prime-boost immunization protocol in which mice were intranasally primed with AdTC_0037 and subcutaneously boosted with recombinant TC_0037 and Toll-like receptor 4 agonist monophosphoryl lipid A mixed in a squalene nanoscale emulsion. We found that immunization with TC_0037 antigen induced specific humoral and T cell responses, decreased Chlamydia loads in the genital tract, and abrogated pathology of upper genital organs. Together, our results suggest that TC_0037, a highly conserved chlamydial T3SS protein, is a good candidate for inclusion in a Chlamydia vaccine

Camelid VHHs Fused to Human Fc Fragments Provide Long Term Protection Against Botulinum Neurotoxin A in Mice

The bacterium Clostridium botulinum is the causative agent of botulism—a severe intoxication caused by botulinum neurotoxin (BoNT) and characterized by damage to the nervous system. In an effort to develop novel C. botulinum immunotherapeutics, camelid single-domain antibodies (sdAbs, VHHs, or nanobodies) could be used due to their unique structure and characteristics. In this study, VHHs were produced using phage display technology. A total of 15 different monoclonal VHHs were selected based on their comlementarity-determining region 3 (CDR3) sequences. Different toxin lethal dose (LD50) challenges with each selected phage clone were conducted in vivo to check their neutralizing potency. We demonstrated that modification of neutralizing VHHs with a human immunoglobulin G (IgG)1 Fc (fragment crystallizable) fragment (fusionbody, VHH-Fc) significantly increased the circulation time in the blood (up to 14 days). At the same time, VHH-Fc showed the protective activity 1000 times higher than monomeric form when challenged with 5 LD50. Moreover, VHH-Fcs remained protective even 14 days after antibody administration. These results indicate that this VHH-Fc could be used as an effective long term antitoxin protection against botulinum type A