mimmunМедицинская иммунологияMedical Immunology (Russia)1563-06252313-741XSPb RAACI10.15789/1563-0625-LVC-2060mimmun-2060Research ArticleОБЗОРЫREVIEWSВирус Ласса: характеристика инфекционного агента, биологические модели для исследования патогенеза, варианты вакцинных препаратовLassa virus: characterization of infectious agent, biological models for pathogenesis studies and variants of vaccinehttps://orcid.org/0000-0002-1856-6147КазачинскаяЕ. И.KazachinskayaE. I.

Казачинская Елена Ивановна– д.б.н., ведущий научныйтсотрудник отдела экспериментального моделированиятпатогенеза инфекционных заболеваний; ведущий научный сотрудник отдела биоинженерии

630559, Новосибирская обл., р. п. Кольцово, 32-1

Kazachinskaya Elena I. - PhD, MD (Biology), Leading Research Associate, Department of Experimental Pathogenesis Modeling of Infectious Diseases; Leading Research Associate, Department of Bioengineering

630559, Novosibirsk Region, Koltsovo, 32-1.

lena.kazachinskaia@mail.ruАриповВ. С.AripovV. S.

аспирант, стажер-исследователь отдела биоинженерии

р. п. Кольцово, Новосибирская обл.

Postgraduate Student, Research Trainee, Department of Bioengineering

Koltsovo, Novosibirsk Region

aripov_vs@vector.nsc.ruЗайковскаяА. В.ZaikovskayaA. V.

к.б.н., старший научный сотрудник отдела «Коллекция микроорганизмов»

р. п. Кольцово, Новосибирская обл.

PhD (Biology), Senior Research Associate, Department “Collection of Microorganisms”

Koltsovo, Novosibirsk Region

zaykovskaya_av@vector.nsc.ruШестопаловА. М.ShestopalovA. M.

д.б.н., профессор, заведующий отделом экспериментального моделированияпатогенеза инфекционных заболеваний

г. Новосибирск

PhD, MD (Biology), Professor, Head, Department of Experimental Pathogenesis Modeling of Infectious Diseases

Novosibirsk

shestopalov2@mail.ruФГБНУ «Федеральный исследовательский центр фундаментальной и трансляционной медицины» Министерства науки и высшего образования РФ; ФБУН «Государственный научный центр вирусологии и биотехнологии “Вектор”» РоспотребнадзораРоссияFederal Research Center for Fundamental and Translational Medicine; Vector State Research Centre of Virology and BiotechnologyRussian FederationФБУН «Государственный научный центр вирусологии и биотехнологии “Вектор”» РоспотребнадзораРоссияVector State Research Centre of Virology and BiotechnologyRussian FederationФГБНУ «Федеральный исследовательский центр фундаментальной и трансляционной медицины» Министерства науки и высшего образования РФРоссияFederal Research Center for Fundamental and Translational MedicineRussian Federation2021260220212313548Copyright © Казачинская Е.И., Арипов В.С., Зайковская А.В., Шестопалов А.М., 20212021Казачинская Е.И., Арипов В.С., Зайковская А.В., Шестопалов А.М.Kazachinskaya E.I., Aripov V.S., Zaikovskaya A.V., Shestopalov A.M.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://www.mimmun.ru/mimmun/article/view/2060

Вирус Ласса (Lassa virus, LASV), отнесенный к роду Mammarenavirus семейства Arenaviridae, является этиологическим агентом лихорадки Ласса (ЛЛ) – заболевания, широко распространенного в Африке и которое протекает без симптомов в среднем у четырех из пяти инфицированных. Ежегодная заболеваемость колеблется от 100 до 500 тыс. зарегистрированных клинических cлучаев с летальностью 1-2% от этого числа, но среди госпитализированных пациентов с тяжелыми симптомами геморрагической лихорадки этот показатель может быть от 14 до 89,5%. Открытое кровотечение и нарушения ЦНС (судороги, тремор, дезориентация и кома) являются признаками неблагоприятного исхода. Смерть наступает от полиорганной недостаточности. У тяжело переболевших людей при медленно протекающей реконвалесценции возможны рецидивы заболевания и осложнения – пневмонии, миокардиты, психозы, потеря слуха.

На эндемичных территориях передача вируса происходит алиментарным, воздушно-пылевым и воздушно-капельным путем от зоонозного источника – грызунов вида «африканская многососковая крыса» (Mastomys natalensis), при случайном контакте людей с выделениями (мочой, калом, слюной) животных, а также при разделывании тушек и употреблении в пищу. Для этих грызунов характерно бессимптомное носительство, сопровождаемое пожизненной персистенцией вируса. Описаны случаи передачи вируса от человека к человеку через кровь или другие биологические жидкости организма заболевших. Больной человек является источником инфекции в течение двух месяцев, т.к. вирус циркулирует в крови на фоне высокого уровня антител. Инфицирование медицинских работников происходит при экстренных хирургических операциях или при несоблюдении правил контактных мер предосторожности. В настоящее время, при продолжающейся с 2016 г. вспышке ЛЛ в Нигерии, в больницах зарегистрированы 22 и 8%-ные уровни летальности пациентов и медицинских работников соответственно. В течение 1969-2016 гг. описано 33 импортированных случая этой болезни из Западной Африки на не эндемичные территории (в США, Канаду, Великобританию, Нидерланды, Германию, Израиль и Японию). Летальность среди этих заболевших составила 39%.

Отсутствие профилактических вакцин и специфических терапевтических препаратов является основной проблемой для профилактики ЛЛ, в связи с этим в данном обзоре рассматриваются биологические модели (культуры клеток и животные), подходящие для изучения патогенеза этой болезни, доклинического исследования специфической активности и безвредности кандидатных вакцин, а также варианты этих разработок на основе таких платформ, как: инактивированный LASV и его ДНК, реассортант аренавируса Мопея, аттенуированные штаммы вирусов желтой лихорадки и кори, рекомбинантные и репликативно-дефектные вирусы (осповакцины, венесуэльского энцефалита лошадей, везикулярного стоматита крупного рогатого скота, аденовируса шимпанзе) и вирусоподобные частицы.

Lassa virus (LASV) is classified into genus Mammarenavirus of Arenaviridae family. This virus is etiological agent of Lassa fever (LF) which is widespread in Africa. On average, in four out of five infected people, LF occurs without symptoms. The annual incidence ranges from 100,000 to 500,000 registered clinical cases, at a mortality rate of 1-2%. Among hospitalized patients with severe symptoms of hemorrhagic fever, this figure may be from 14 to 89.5%. Signs of an adverse outcome in LF are open bleeding and disorders of CNS (convulsions, tremor, disorientation and coma). Death occurs from multiple organ failure. Severely ill people recover slowly and may have relapses and complications such as pneumonia, myocarditis, psychosis, and hearing loss.

Transmission of the virus in endemic territories occurs by alimentary way, air-dust and airborne droplets from a zoonotic source – rodents of the species African multimammate rat (Mastomys natalensis), by accidental contacts of people with their secretions (urine, feces, saliva) as well as when butchering carcasses and eating rodents. These animals are characterized by asymptomatic carrier and life-long persistence of the virus. Cases of transmission of the virus from person to person through the blood or other body fluids of patients are described. A sick person is contagious for two months, because the virus circulates in the blood despite high levels of antibodies. Infection of medical staff occurs during emergency surgical operations, or when the rules of contact precautions are not observed. Currently, with the ongoing LF outbreak in Nigeria, since 2016, hospitals have registered mortality rates of 22 and 8% for patients and health workers, respectively. During 1969-2016, 33 imported cases of this disease were described from West Africa to non-endemic territories (in the USA, Canada, Great Britain, the Netherlands, Germany, Israel and Japan). The mortality rate among these patients was 39%.

The lack of prophylactic vaccines and specific therapeutic drugs is the major challenge for the prevention of LF. Thus, this review considers biological models (cell cultures and animals) that are suitable for studying the pathogenesis of this disease, preclinical studies of the specific activity and harmlessness of candidate vaccines, as well as options for these developments based on the platforms such as inactivated LASV and its DNA, the reassortant of Mopeia arenavirus, and measles virus attenuated strains, recombinant and replication-defective viruses (smallpox vaccine, Venezuelan equine encephalitis, bovine vesicular stomatitis, adenovirus of chimpanzee) and virus-like particles.

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The authors declare that there are no conflicts of interest present.