Background Severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) is responsible for the ongoing global COVID‐19 pandemic. One possibility to control the pandemic is to induce sterilizing immunity through the induction and maintenance of neutralizing antibodies preventing SARS‐CoV‐2 from entering human cells to replicate in. Methods We report the construction and in vitro and in vivo characterization of a SARS‐CoV‐2 subunit vaccine (PreS‐RBD) based on a structurally folded recombinant fusion protein consisting of two SARS‐CoV‐2 Spike protein receptor‐binding domains (RBD) fused to the N‐ and C‐terminus of hepatitis B virus (HBV) surface antigen PreS to enable the two unrelated proteins serving as immunologic carriers for each other. Results PreS‐RBD, but not RBD alone, induced a robust and uniform RBD‐specific IgG response in rabbits. Currently available genetic SARS‐CoV‐2 vaccines induce mainly transient IgG 1 responses in vaccinated subjects whereas the PreS‐RBD vaccine induced RBD‐specific IgG antibodies consisting of an early IgG 1 and sustained IgG 4 antibody response in a SARS‐CoV‐2 naive subject. PreS‐RBD‐specific IgG antibodies were detected in serum and mucosal secretions, reacted with SARS‐CoV‐2 variants, including the omicron variant of concern and the HBV receptor‐binding sites on PreS of currently known HBV genotypes. PreS‐RBD‐specific antibodies of the immunized subject more potently inhibited the interaction of RBD with its human receptor ACE2 and their virus‐neutralizing titers (VNTs) were higher than median VNTs in a random sample of healthy subjects fully immunized with registered SARS‐CoV‐2 vaccines or in COVID‐19 convalescent subjects. Conclusion The PreS‐RBD vaccine has the potential to serve as a combination vaccine for inducing sterilizing immunity against SARS‐CoV‐2 and HBV by stopping viral replication through the inhibition of cellular virus entry.
Autophagy is a highly conserved lysosomal degradation system that involves the creation of autophagosomes, which eventually fuse with lysosomes and breakdown misfolded proteins and damaged organelles with their enzymes. Autophagy is widely known for its function in cellular homeostasis under physiological and pathological settings. Defects in autophagy have been implicated in the pathophysiology of a variety of human diseases. The new line of evidence suggests that autophagy is inextricably linked to skin disorders. This review summarizes the principles behind autophagy and highlights current findings of autophagy’s role in skin disorders and strategies for therapeutic modulation.
Neutrophils are the most numerous cells in the leukocyte population and essential for innate immunity. To limit their effector functions, neutrophils are able to modulate glycolysis and other cellular metabolic pathways. These metabolic pathways are essential not only for energy usage, but also for specialized effector actions, such as the production of reactive oxygen species (ROS), chemotaxis, phagocytosis, degranulation, and the formation of neutrophil extracellular traps (NETs). It has been demonstrated that activated viable neutrophils can produce NETs, which consists of a DNA scaffold able to bind granule proteins and microorganisms. The formation of NETs requires the availability of increased amounts of adenosine triphosphate (ATP) as it is an active cellular and therefore energy-dependent process. In this article, we discuss the glycolytic and other metabolic routes in association with neutrophil functions focusing on their role for building up NETs in the extracellular space. A better understanding of the requirements of metabolic pathways for neutrophil functions may lead to the discovery of molecular targets suitable to develop novel anti-infectious and/or anti-inflammatory drugs.
Use of azoximer bromide for treatment of children's inflammatory infections of respiratory system: a meta-analysis of controlled clinical studies.
The aim of the study was to determine efficiency of Glutoxim, aimed for correction of immune disorders. The drug was administered to the patients with chronic cerebral ischemia (CCI, Stage I and II) complicated by arterial hypertension. Increased contents of pro-and anti-inflammatory cytokines, IFNγ, IL-2, G-CSF, and activation of the complement system have been revealed for these conditions, at both functional stages of the disease. The patients with stage II CCI showed elevated markers of oxygen-dependent activity in polymorphonuclear leukocytes (increased levels of spontaneous and stimulated nitroblue tetrazolium (NBT) reduction tests, phagocytic capacity and stimulation index of neutrophils). Stage I of chronic cerebral ischemia was characterized by normal values of NBT reduction tests and functional reserve of neutrophils, along with decreased stimulation index of neutrophils. Among 26 parameters of immune status, 73.1% and 80.8% of indices proved to be changed, respectively, in the patients with stage I and II CCI. 66.7% of immune indices appeared similar in magnitude and direction of changes, whereas the resting 33% are identical in orientation. Usage of Cereton and Actovegin in treatment of the stage I CCI caused normalization of 5.3% immune parameters, with partial normalization of 26.3% tests, and 68.4% of the indexes remaining unchanged or increased posttreatment. Inclusion of Glutoxim into the combined pharmacotherapy proved to be more effective since it totally normalized 52.6% of the indexes, along with partial normalization of 21.1%, while 26.3% of the indicators were not affected by the therapy. Administration of Cereton and Actovegin at the second stage of chronic brain ischemia was followed by partial normalization for 47,6% of the tests, while leaving unchanged or increased 52.4% of the indicators. Glutoxim Use fully normalize 19.0% and partially normalizes 57.1% of immune parameters.
Клинико-экономическая оценка эффективности и безопасности существующей практики проведения периоперационной антибиотикопрофилактики на оcнове фармакоэпидемиологического исследования в многопрофильных стационарах Санкт-Петербурга Применение метода многокритериального анализа принятия решений (MCDA) для разработки инструмента оценки уровня терапевтической ценности (инновационности) оригинальных лекарственных препаратов Том 10
1 ФГАОУ ВО Первый МГМУ им. И. М. Сеченова Минздрава России (Сеченовский Университет) Минздрава России, Москва 2 НПО Петровакс Фарм, Москва Обзор исследований вакцин семейства Гриппол и развития современных адъювантов Резюме Актуальность. Вакцинация остается основой профилактики наиболее значимых инфекционных заболеваний, включая грипп. На сегодняшний день разработано и применяется большое число вакцин, в том числе с применением различных адьювантов. Цель работы. Углубиться в историю поиска эффективных адъювантов и провести обзор клинических исследований вакцин семейства Гриппол; обобщить данные о значимости адъювантных вакцин, содержащих Полиоксидоний, который более 22 лет применяется для производства вакцин Гриппол. Вывод. Вакцина Гриппол ® показала высокий профиль безопасности и хорошую иммуногенность у привитых, в том числе у лиц с низкой отвечаемостью. В 2008 г. в России была зарегистрирована вакцина Гриппол ® плюс, содержащая сниженное количество антигенов и адъювант Полиоксидоний, но в отличие от вакцины Гриппол ® , лишенная консерванта тиомерсала. В многочисленных исследованиях с участием разных контингентов не отмечено серьезных поствакцинальных явлений, неожиданных реакций, осложнений на прививку. Вакцина Гриппол ® плюс эффективно индуцировала иммунный ответ. Доказано, что адъювантные вакцины Гриппол ® и Гриппол ® плюс со сниженным содержанием антигенов являются безопасными и эффективными препаратами и при массовом применении обладают хорошей профилактической эффективностью. В 2018 г. в России была зарегистрирована новая четырехвалентная гриппозная вакцина группы «Гриппол» -Гриппол ® Квадривалент. Клинические исследования 1-2 фазы показали, что вакцина соответствует критериям иммуногенности для инактивированных гриппозных вакцин. Продолжаются клинические исследования 3-й фазы по расширению показаний к применению данной вакцины. Все вакцины группы «Гриппол» имеют высокий профиль безопасности -уменьшение дозы вирусных антигенов снижает риск развития нежелательных реакций у вакцинированных. Полиооксидоний в вакцине в качестве адъюванта эффективно стимулирует иммунный ответ, не оказывая негативного влияния на организм вакцинируемого. Отмечено, что физико-химические свойства Полиоксидония (МНН: Азоксимер бромид) позволяют рассматривать его в качестве универсального адъюванта для других антигенов. Ключевые слова: вакцины против гриппа с адъювантом, Гриппол, Гриппол ® плюс, Гриппол ® Квадривалент, Полиоксидоний Конфликт интересов Караулов А. В., Быков А. С. -конфликт интересов не заявлен. Н. В. Волкова -сотрудник НПО Петровакс ФАРМ. Abstract Relevance. Vaccination remains the basis for the prevention of the most severe infectious diseases, including the prevention of influenza. The large number of vaccines have been developed and applied currently. The role of adjuvant vaccines is growing. Aims: To look back to the history of adjuvant vaccines and review the literature on clinical trials of influenza vaccines Grippol family. Conclusions: This review summarized principal data on adjuvanted vaccines containing Po...
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