microbeПроблемы особо опасных инфекцийProblems of Particularly Dangerous Infections0370-10692658-719XRussian Research Anti-Plague Institute “Microbe”10.21055/0370-1069-2023-4-24-31microbe-1893Research ArticleОБЗОРЫREVIEWSСравнение эффективности различных схем применения рекомбинантных векторных вакцин против лихорадки Эбола на основе вируса вакцины, штамм MVAComparison of the Efficacy of Different Schemes for Using Recombinant Vector Vaccines against Ebola Fever, Based on Vaccinia Virus, MVA Strainhttps://orcid.org/0000-0002-7985-5516СтовбаЛ. Ф.StovbaL. F.

141306, Московская обл., Сергиев Посад-6, ул. Октябрьская, 11

11, Oktyabrskaya St., Sergiev Possad-6, Moscow Region, 141306

https://orcid.org/0000-0002-2603-0860ЧухраляО. В.ChukhralyaO. V.

141306, Московская обл., Сергиев Посад-6, ул. Октябрьская, 11

11, Oktyabrskaya St., Sergiev Possad-6, Moscow Region, 141306

https://orcid.org/0000-0003-3204-1897ПавельевД. И.Pavel’evD. I.

141306, Московская обл., Сергиев Посад-6, ул. Октябрьская, 11

11, Oktyabrskaya St., Sergiev Possad-6, Moscow Region, 141306

https://orcid.org/0000-0002-1491-6293ЧерниковаН. К.ChernikovaN. K.

141306, Московская обл., Сергиев Посад-6, ул. Октябрьская, 11

11, Oktyabrskaya St., Sergiev Possad-6, Moscow Region, 141306

https://orcid.org/0000-0002-6742-3919БорисевичС. В.BorisevichS. V.

11, Oktyabrskaya St., Sergiev Possad-6, Moscow Region, 141306

11, Oktyabrskaya St., Sergiev Possad-6, Moscow Region, 141306

48cnii@mil.ruФГБУ «48 Центральный научно-исследовательский институт» Министерства обороны Российской ФедерацииРоссия48th Central Research Institute of the Ministry of Defense of the Russian FederationRussian Federation202307012024042431Copyright © Стовба Л.Ф., Чухраля О.В., Павельев Д.И., Черникова Н.К., Борисевич С.В., 20242024Стовба Л.Ф., Чухраля О.В., Павельев Д.И., Черникова Н.К., Борисевич С.В.Stovba L.F., Chukhralya O.V., Pavel’ev D.I., Chernikova N.K., Borisevich S.V.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://journal.microbe.ru/jour/article/view/1893

Цель обзора – оценка применения вакцин на основе вируса вакцины, штамм MVA, и аденовирусных векторов для профилактики болезни, вызываемой вирусом Эбола. Рассмотрены рекомбинантные штаммы MVA, экспрессирующие антигенные детерминанты представителей семейства филовирусов как возможные кандидаты в вакцинные препараты. Применение этого вируса в качестве вакцинного вектора обусловлено отсутствием противооспенного популяционного иммунитета и его безопасностью для здоровых взрослых волонтеров, для детей, подростков и лиц, больных туберкулезом, людей в возрасте 56–80 лет, лиц, больных атопическим дерматитом, СПИДом. Кроме того, иммунизация вакциной на основе вируса вакцины, штамм MVA, не вызывает осложнений со стороны сердечно-сосудистой системы. Доклиническая оценка иммуногенности и защитной эффективности проводилась на иммунокомпетентных и иммунокомпромиссных мышах, морских свинках, адаптированных к вирусу Эбола, обезьянах макаках-резусах и макаках cynomolgus. Представлены результаты экспериментов по созданию вакцин, экспрессирующих либо только вирусный гликопротеин, либо вирусный гликопротеин и структурный белок Vp40. Поскольку вспышки лихорадки Эбола и других филовирусных инфекций трудно спрогнозировать, были созданы мультивалентные вакцины, которые будут защищать против всех филовирусных видов. Клинические испытания по применению в одном и том же эксперименте вакцин на основе рекомбинантных аденовирусных векторов и штамма MVA подтвердили более выраженную безопасность вакцин на основе рекомбинантного штамма MVA. Результаты индуцированного гуморального и Т-клеточного иммунных ответов показали, что этот вектор целесообразнее применять в качестве бустерного при гетерологичной прайм/бустерной схеме иммунизации. Оценены схемы вакцинации для формирования сильного длительного иммунитета. Эпидемиологическое моделирование установило, что профилактическая иммунизация, вызывающая длительный иммунитет у здорового населения в местах с высоким эпидемическим риском, будет предпочтительнее для ограничения будущих вспышек по сравнению с кольцевой иммунизацией, что было показано в кампании по ликвидации натуральной оспы в мире. Повышенный уровень иммунитета, индуцируемый при прайм/бустерной схеме иммунизации, сохраняющийся в течение длительного времени, будет иметь преимущество над ускоренной кольцевой иммунизацией, когда длительность защиты является более важным фактором, чем скорость, с которой эта защита формируется.

The aim of this review was to investigate the use of the vaccines based on vaccinia virus, MVA stain, and adenovirus vectors for the prevention of Ebola virus disease. The recombinant MVA strains expressing antigen determinants of Filoviridae family representatives were assessed as possible candidates for vaccine preparations. Application of this virus as a vaccine vector is conditioned by the absence of herd immunity to smallpox and its safety for healthy adult volunteers, children, adolescents, individuals suffering from tuberculosis, persons aged 56–80 years, people with diagnosed atopic dermatitis, AIDS. Furthermore, immunization with the vaccine on the basis of vaccinia virus, MVA strain, does not cause complications associated with cardiovascular diseases. Preclinical trials on immunogenicity and protective efficiency were carried out on immune-competent and immune-compromised mice; guinea pigs adapted to Ebola virus; rhesus macaques and cynomolgus monkeys. Presented are the results of experiments on the creation of vaccines expressing either only viral glycoprotein or viral glycoprotein and structural protein Vp40. Given that Ebola fever and other filovirus infection outbreaks are hard to predict, multivalent vaccines that would be able to provide protection against all filovirus species were designed. Clinical trials on simultaneous use of the vaccines based on recombinant adenovirus vectors and MVA strain showed more pronounced safety of vaccines on the basis of recombinant MVA strain. Studies of humoral and T-cell immune responses have revealed that this vector is more suitable for booster vaccination in case of heterologous prime/booster immunization scheme. Vaccination regimens for forming strong durable immune responses have been analyzed. Epidemiological modeling provided evidence that preventive immunization leading to long-term immunity in healthy population in areas of high epidemic risk will be of greater benefit in terms of controlling future outbreaks compared to ring immunization that was effective during smallpox eradication campaign. Increased immunity level, induced by prime/booster vaccination, persisting for a long period of time, will have an advantage over accelerated ring immunization; when the duration of protection is more significant than the speed it is formed at.

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