mimmunМедицинская иммунологияMedical Immunology (Russia)1563-06252313-741XSPb RAACI10.15789/1563-0625-PQI-2346mimmun-2346Research ArticleОБЗОРЫREVIEWSПроблемные вопросы при разработке средств специфической профилактики лихорадки денгеProblematic questions in the development of specific prevention of dengue feverhttps://orcid.org/0000-0002-1856-6147КазачинскаяЕ. И.KazachinskaiaE. I.

Д.б.н., ведущий научный сотрудник отдела экспериментального моделирования патогенеза инфекционных заболеваний ФГБНУ «Федеральный исследовательский центр фундаментальной и трансляционной медицины»; ведущий научный сотрудник отдела биоинженерии ФБУН «Государственный научный центр вирусологии и биотехнологии «Вектор» Роспотребнадзора

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

Тел.: 8 (909) 530-74-41

PhD, MD (Biology), Leading Research Associate, Department of Experimental Modeling of Pathogenesis of Infectious Diseases, Federal Research Center for Fundamental and Translational Medicine; Leading Research Associate, Department of Bioengineering, State Research Centre of Virology and Biotechnology “Vector”

630559, Novosibirsk Region, Koltsovo, 32-1

Phone: 7 (909) 530-74-41

lena.kazachinskaia@mail.ruШаньшинД. В.ShanshinD. V.

Младший научный сотрудник отдела биоинженерии

р. п. Кольцово, Новосибирская обл.

Junior Research Associate, Department of Bioengineering

Koltsovo, Novosibirsk Region

shanshin_dv@vector.nsc.ruЩербаковД. Н.ScherbakovD. N.

Ведущий научный сотрудник, заведующий лабораторией иммунохимии отдела биоинженерии

р. п. Кольцово, Новосибирская обл.

PhD (Biology), Leading Research Associate, Department of Bioengineering

Koltsovo, Novosibirsk Region

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

Д.б.н., профессор, заведующий отделом экспериментального моделирования патогенеза инфекционных заболеваний

г. Новосибирск

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

Novosibirsk

shestopalov2@mail.ruФГБНУ «Федеральный исследовательский центр фундаментальной и трансляционной медицины»; ФБУН «Государственный научный центр вирусологии и биотехнологии «Вектор» РоспотребнадзораРоссияFederal Research Center for Fundamental and Translational Medicine; State Research Centre of Virology and Biotechnology “Vector”Russian FederationФБУН «Государственный научный центр вирусологии и биотехнологии «Вектор» РоспотребнадзораРоссияState Research Centre of Virology and Biotechnology “Vector”Russian FederationФГБНУ «Федеральный исследовательский центр фундаментальной и трансляционной медицины»РоссияFederal Research Center for Fundamental and Translational MedicineRussian Federation2022100320222411930Copyright © Казачинская Е.И., Шаньшин Д.В., Щербаков Д.Н., Шестопалов А.М., 20222022Казачинская Е.И., Шаньшин Д.В., Щербаков Д.Н., Шестопалов А.М.Kazachinskaia E.I., Shanshin D.V., Scherbakov D.N., 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/2346

Лихорадка денге, известная, по литературным источникам, с эпохи династии Цинь (265-420 гг.), развивается у человека при укусе комарами рода Aedes, инфицированных вирусом денге (dengue virus, DENV) и проявляется как гриппоподобное заболевание. Лихорадочное состояние может сопровождаться диспепсическими расстройствами (тошнотой, рвотой, диареей) и сыпью. Приблизительно 1-2% случаев инфекции клинически представлены как наиболее тяжелая форма – это геморрагическая лихорадка денге/синдром шока денге (dengue hemorrhagic fever/dengue shock syndrome (DHF/DSS), приводящие в эндемичных районах к 500 тыс. ежегодных госпитализаций с летальностью около 5%. Четыре генетически удаленных серотипа DENV (1, 2, 3 и 4), открытые в середине XX в., классифицируются как разные виды вирусов внутри одного антигенного комплекса и имеют почти идентичную эпидемиологическую картину вызываемых ими заболеваний. В 2013 г. был выделен новый серотип DENV-5. До 1980-х гг. в большинстве географических регионов мира, где регистрировалась лихорадка денге, выявлялся вирус, относящийся только к одному или двум серотипам. С течением времени наблюдается увеличение ко-циркуляции четырех видов вирусов, что может служить ключевым индикатором их глобального распространения. По мере того, как «следы» четырех видов DENV все больше пересекаются, угроза развития тяжелой болезни возрастает из-за феномена антитело-зависимого усиления инфекции при повторном инфицировании гетерологичным вирусным серотипом.

Разработка средств специфической профилактики лихорадки денге ведется с 1944 г. (с момента выделения этиологического возбудителя этой болезни), но первая и пока единственная лицензированная в 2015 г. четырехвалентная вакцина – Dengvaxia, разработанная французской фармацевтической компанией Sanofi Pasteur, оказалась в разной степени эффективна при инфицировании каждым из вирусных серотипов и, кроме того, опасной для ранее серонегативных людей. Исследования, направленные на получение безопасной и эффективной вакцины, продолжаются. Нейтрализующие моноклональные антитела являются необходимым инструментом изучения антигенной структуры вирусных иммуногенов – основы профилактических препаратов против лихорадки денге.

Dengue fever known from literary sources since the Qin dynasty (265-420) is caused in humans when bitten by Aedes mosquitoes infected with the dengue virus (DENV) and manifests as a flu-like disease. A feverish state can be accompanied by dyspeptic disorders (nausea, vomiting, diarrhea) and a rash. Approximately 1-2% of infections are clinically presented as the most severe form – it is dengue hemorrhagic fever/dengue shock syndrome (DHF/DSS) leading to 500 thousand annual hospitalizations with a mortality rate of about 5% in endemic areas.

Four genetically removed DENV serotypes (1, 2, 3, and 4) are classified as different types of viruses within the same antigen complex and have almost identical epidemiological features. In 2013 a new serotype DENV-5 was isolated.

Until the 1980s in most geographical regions of the world where dengue fever was registered only one or two viral serotypes were detected as an etiological agent of the disease. Over time there is an increase in the cocirculation of four types of viruses which can serve as a key indicator of their global spread. As the “traces” of the four DENV species overlap more and more the threat of severe disease increases due to the phenomenon of antibody-dependent of infection when re-infected with a heterologous viral serotype.

Development of specific dengue fever prevention has been underway since 1944 (since the discovery of viral agents of this disease) but the first and so far only licensed in 2015 tetravalent vaccine-Dengvaxia developed by the French pharmaceutical company Sanofi Pasteur has been effective in varying degrees of protection against infection with each of the viral serotypes and in addition dangerous for previously seronegative people. Research aimed at obtaining a safe and effective vaccine is continuing. Neutralizing monoclonal antibodies are a necessary tool for studying the antigenic structure of viral immunogens as base of prevention preparates against dengue fever.

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