microbeПроблемы особо опасных инфекцийProblems of Particularly Dangerous Infections0370-10692658-719XRussian Research Anti-Plague Institute “Microbe”10.21055/0370-1069-2018-3-8-15microbe-495Research ArticleОБЗОРЫREVIEWSЭкспериментальные вакцины для профилактики геморрагической лихорадки Марбург и биомодели для изучения ее патогенезаExperimental Vaccines for Prevention of Marburg Hemorrhagic Fever and Animal Models for Studying PathogenesisВолковаН. В.VolkovaN. V.

630559, Новосибирская  обл.,  п. Кольцово

Kol’tsovo, Novosibirsk Region, 630559

tasha_wolkowa11.93@mail.ruКазачинскаяЕ. И.KazachinskayaE. I.

630559, Новосибирская  обл.,  п. Кольцово

Kol’tsovo, Novosibirsk Region, 630559

ЩербаковД. Н.ShcherbakovD. N.

630559, Новосибирская  обл.,  п. Кольцово

Kol’tsovo, Novosibirsk Region, 630559

ФБУН «Государственный научный центр вирусологии и биотехнологии «Вектор», КольцовоРоссияState Scientific Centre of Virology and Biotechnology “Vector”, Kol’tsovoRussian Federation20180310201803815Copyright © Волкова Н.В., Казачинская Е.И., Щербаков Д.Н., 20182018Волкова Н.В., Казачинская Е.И., Щербаков Д.Н.Volkova N.V., Kazachinskaya E.I., Shcherbakov D.N.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/495

Лихорадка Марбург – острое природно-очаговое заболевание, характеризующееся тяжелым течением, геморрагическим синдромом, высоким уровнем контагиозности и летальности. Возбудителем заболевания является РНК-содержащий вирус, принадлежащий к семейству филовирусов (Filoviridae). Отсутствие вакцин и профилактических препаратов является основной проблемой, с которой сталкиваются врачи и ученые, участвующие в борьбе с лихорадкой Марбург. Разработка эффективных вакцин актуальна для защиты населения, проживающего в природных очагах и медицинского персонала в очагах эпидемий, а также для обеспечения безопасной научной работы в лабораториях BSL-4. В обзоре рассматриваются биомодели, подходящие для изучения патогенеза филовирусных инфекций, доклинического исследования специфической активности и безвредности кандидатных вакцин против лихорадки Марбург, а также различные варианты этих вакцин.

Marburg fever is an acute natural-focal disease characterized by severe course, hemorrhagic syndrome, high level of contagiousness and lethality. The causative agent of the disease is the RNA-containing virus belonging to the family of filoviruses (Filoviridae). The main problem faced by doctors and scientists involved in the fight against Marburg fever is the lack of vaccines and preventive drugs against this disease. The development of effective vaccines against filovirus infection is relevant for protecting the population living in natural foci and medical personnel during epidemic outbreaks, as well as for ensuring safe research work in BSL-4 laboratories. In this regard, this review considers biomodels suitable for studying the pathogenesis of filovirus infections, preclinical studies of specific activity and harmlessness of prototype Marburg virus vaccines and variants of these vaccines.

вирус Марбург (MARV)биомоделивакциныMarburg virus (MARV)animal modelsvaccinesРабота выполнена в рамках темы ГЗ-№ 2904-р плана основных мероприятий ФБУН ГНЦ ВБ «Вектор» Роспотребнадзора на 2018 г.ReferencesSiegert R., Shu H.L., Slenczka W., Peters D, Müller G. On the etiology of an unknown human infection originating from monkeys. Dtsch. Med. Wochenschr.1967; 92(51):2341–3. DOI: 10.1055/s-0028-1106144.Siegert R., Shu H.L., Slenczka W., Peters D, Müller G. On the etiology of an unknown human infection originating from monkeys. Dtsch. Med. Wochenschr.1967; 92(51):2341–3. DOI: 10.1055/s-0028-1106144.Negredo A., Palacios G., Vazquez-Moron S., Gonzalez F., Dopazo H., Molero F., Juste J., Quetglas J., Savji N., dela CruzMartinez M., Herrera J.E., Pizarro M., Hutchison S.K., Echevarria J.E., Lipkin W.I., Tenorio A. Discovery of an EbolavirusLike Filovirus in Europe. PLoS Pathog. 2011; 7(10):e1002304. DOI: 10.1371/journal.ppat.1002304.Negredo A., Palacios G., Vazquez-Moron S., Gonzalez F., Dopazo H., Molero F., Juste J., Quetglas J., Savji N., dela CruzMartinez M., Herrera J.E., Pizarro M., Hutchison S.K., Echevarria J.E., Lipkin W.I., Tenorio A. Discovery of an EbolavirusLike Filovirus in Europe. PLoS Pathog. 2011; 7(10):e1002304. DOI: 10.1371/journal.ppat.1002304.Beer B., Kurth R., Bukreyev A. Characteristics of Filoviridae: Marburg and Ebola viruses. Naturwissenschaften. 1999; 86(1):8–17. DOI: 10.1007/s001140050562.Beer B., Kurth R., Bukreyev A. Characteristics of Filoviridae: Marburg and Ebola viruses. Naturwissenschaften. 1999; 86(1):8–17. DOI: 10.1007/s001140050562.Никифоров В.В., Туровской Ю.И, Калинин П.П. Случай лабораторного заражения лихорадкой Марбург. Микробиология. 1994; 63(3):104–10.Nikiforov V.V., Turovskoi Yu.I., Kalinin P.P. [A case of laboratory infection with Marburg fever]. Mikrobiologiya. 1994; 63(3):104–10. (In Russ.)Towner J.S., Khristova M.L., Sealy T.K., Vincent M. J., Erickson B. R., Bawiec D.A., Hartman A. L., Comer J. A., Zaki S.R Ströher U., Gomes da Silva F, del Castillo F., Rollin P. E., Ksiazek T. G., Nichol1 S. T. Marburgvirus genomics and association with a large hemorrhagic fever outbreak in Angola. J. Virol.2006; 80(13):6497–6. DOI: 10.1128/JVI.00069-06.Towner J.S., Khristova M.L., Sealy T.K., Vincent M. J., Erickson B. R., Bawiec D.A., Hartman A. L., Comer J. A., Zaki S.R Ströher U., Gomes da Silva F, del Castillo F., Rollin P. E., Ksiazek T. G., Nichol1 S. T. Marburgvirus genomics and association with a large hemorrhagic fever outbreak in Angola. J. Virol. 2006; 80(13):6497–6. DOI: 10.1128/JVI.00069-06.Mire C.E., Geisbert J.B., Agans K.N., Satterfield B.A., Versteeg K.M., Fritz E.A., Feldmann H., Hensley L.E., Geisbert T.W. Durability of a vesicular stomatitis virus based Marburg vi-rus vaccine in nonhuman primates. PLoS One.2014; 9(4):e94355. DOI: 10.1371/journal.pone.0094355.Mire C.E., Geisbert J.B., Agans K.N., Satterfield B.A., Versteeg K.M., Fritz E.A., Feldmann H., Hensley L.E., Geisbert T.W. Durability of a vesicular stomatitis virus based Marburg virus vaccine in nonhuman primates. PLoS One. 2014; 9(4):e94355. DOI: 10.1371/journal.pone.0094355.Qiu X., Wong G., Audet J., Cutts T., Niu Y., Booth S., Kobinger G.P. Establishment and characterization of a lethal mouse model for the Angola strain of Marburg virus. J. Virol. 2014; 88(21):12703–14. DOI: 10.1128/JVI.01643-14.Qiu X., Wong G., Audet J., Cutts T., Niu Y., Booth S., Kobinger G.P. Establishment and characterization of a lethal mouse model for the Angola strain of Marburg virus. J. Virol. 2014; 88(21):12703–14. DOI: 10.1128/JVI.01643-14.Sridhar S. Clinical development of Ebola vaccines. Ther. Adv. Vaccines. 2015; 3(5–6):125–38. DOI: 10.1177/2051013615611017.Sridhar S. Clinical development of Ebola vaccines. Ther. Adv. Vaccines. 2015; 3(5–6):125–38. DOI: 10.1177/2051013615611017.Baron R.C., McCormick J.B., Zubeir O.A. Ebola virus disease in southern Sudan. Hospital dissemination and intrafamilial spread. Bull World Health Organ. 1983; 61(6):997–1003. PubMed PMID: 6370486.Baron R.C., McCormick J.B., Zubeir O.A. Ebola virus disease in southern Sudan. Hospital dissemination and intrafamilial spread. Bull World Health Organ. 1983; 61(6):997–1003. PubMed PMID: 6370486.Походаев В.А., Гончар Н.И., пшеничнов В.А. Экспериментальное изучение контактной передачи вируса Марбург. Вопросы вирусологии. 1991; (6): 506–8.Pokhodaev V.A., Gonchar N.I., Pshenichnov V.A. [Experimental study of Marburg virus contact-type transmission]. Voprosy Virusologii. 1991; (6):506–8. (In Russ.)Johnson E., Jaax N., White J. Lethal experimental infection of rhesus monkeys by aerosolized Ebola virus. Int. J. Exp. Pathol.1995; 76(4):227–36. PMCID: PMC1997182.Johnson E., Jaax N., White J. Lethal experimental infection of rhesus monkeys by aerosolized Ebola virus. Int. J. Exp. Pathol. 1995; 76(4):227–36. PMCID: PMC1997182.Kobinger G.P., Leung A., Neufeld J., Richardson J.S., Falzarano D., Smith G., Tierney K., Patel A., Weingartl H.M. Replication, pathogenicity, shedding, and transmission of Zaire ebolavirus in pigs. J. Infect. Dis.2011; 204(2):200–8. DOI: 10.1093/infdis/jir077.Kobinger G.P., Leung A., Neufeld J., Richardson J.S., Falzarano D., Smith G., Tierney K., Patel A., Weingartl H.M. Replication, pathogenicity, shedding, and transmission of Zaire ebolavirus in pigs. J. Infect. Dis.2011; 204(2):200–8. DOI: 10.1093/infdis/jir077.Weingartl H.M., Embury-Hyatt C., Nfon C., Leung A., Smith G., Kobinger G. Transmission of Ebola virus from pigs to nonhuman primates. Sci. Rep. 2012; 2:811. DOI: 10.1038/srep00811.Weingartl H.M., Embury-Hyatt C., Nfon C., Leung A., Smith G., Kobinger G. Transmission of Ebola virus from pigs to nonhuman primates. Sci. Rep. 2012; 2:811. DOI: 10.1038/srep00811.Schuh A.J., Amman B.R., Jones M.E.B., Sealy T.K., Uebelhoer L.S., Spengler J.R., Martin B.E., Coleman-McCray J.A.D., Nichol S.T., Towner J.S. Modelling filovirus maintenance in nature by experimental transmission of Marburg virus between Egyptian rousette bats. Nat. Commun. 2017; 8:14446. DOI: 10.1038/ncomms14446.Schuh A.J., Amman B.R., Jones M.E.B., Sealy T.K., Uebelhoer L.S., Spengler J.R., Martin B.E., Coleman-McCray J.A.D., Nichol S.T., Towner J.S. Modelling filovirus maintenance in nature by experimental transmission of Marburg virus between Egyptian rousette bats. Nat. Commun.2017; 8:14446. DOI: 10.1038/ncomms14446.Телесманич Н.Р., Микашинович З.И., Ломаковский Н.С., Лосева Т.Д., Чайка С.О. Биохимия вируса Эбола и молекулярные аспекты биологической защиты. Журнал фундаментальной медицины и биологии. 2015; (3):28–34.Telesmanich N.R., Mikashinovich Z.I., Lomakovsky N.S., Loseva T.D., Chaika S.O. [Biochemistry of Ebola virus and molecular aspects of biological protection]. Zhurnal Fundamental’noi i Molekulyarnoi Meditsiny i Biologii.2015; (3):28–34. (In Russ.)Matassov D., Mire C.E., Latham T., Geisbert J.B., Xu R., Ota-Setlik A., Agans K.N., Kobs D.J., Wendling M.Q.S., Burnaugh A., Rudge T.L. Jr., Sabourin C.L., Egan M.A., Clarke D.K., Geisbert T.W., Eldridge J.H. Single dose trivalent vesiculovax vaccine protects macaques from lethal Ebolavirus and Marburgvirus challenge. J. Virol. 2017; 92(3):e01190–17. DOI: 10.1128/JVI.01190-17.Matassov D., Mire C.E., Latham T., Geisbert J.B., Xu R., Ota-Setlik A., Agans K.N., Kobs D.J., Wendling M.Q.S., Burnaugh A., Rudge T.L. Jr., Sabourin C.L., Egan M.A., Clarke D.K., Geisbert T.W., Eldridge J.H. Single dose trivalent vesiculovax vaccine protects macaques from lethal Ebolavirus and Marburgvirus challenge. J. Virol. 2017; 92(3):e01190–17. DOI: 10.1128/JVI.01190-17.Paweska J. T., Storm N., Grobbelaar A.A., Markotter W., Kemp A., van Vuren P.J. Experimental inoculation of Egyptian fruit bats (Rousettus aegyptiacus) with Ebola virus. Viruses. 2016; 8(2):E29. DOI: 10.3390/v8020029.Paweska J. T., Storm N., Grobbelaar A.A., Markotter W., Kemp A., van Vuren P.J. Experimental inoculation of Egyptian fruit bats (Rousettus aegyptiacus) with Ebola virus. Viruses. 2016; 8(2):E29. DOI: 10.3390/v8020029.Han Z., Bart S.M., Ruthel G., VandeBurgt N.H., Haines K.M., Volk S.W., Vite C.H., Freedman B.D., Bates P., Harty R.N. Ebola virus mediated infectivity is restricted in canine and feline cells. Vet. Microbiol.2016; 182:102–7. DOI: 10.1016/j.vetmic.2015.11.011.Han Z., Bart S.M., Ruthel G., VandeBurgt N.H., Haines K.M., Volk S.W., Vite C.H., Freedman B.D., Bates P., Harty R.N. Ebola virus mediated infectivity is restricted in canine and feline cells. Vet. Microbiol. 2016; 182:102–7. DOI: 10.1016/j.vetmic.2015.11.011.WHO Report. Ebola Reston vAirus detected pigs in the Philippines. 2009; 14(4):19105. PubMed PMID: 19215709.WHO Report. Ebola Reston virus detected pigs in the Philippines. 2009; 14(4):19105. PubMed PMID: 19215709.Краснянский В.П., Михайлов В.В., Борисевич И.В., Градобоев В.Н., Евсеев А.А., Пшеничнов В.А. Получение гипериммунной лошадиной сыворотки против вируса Эбола. Вопросы вирусологии. 1994; 39(2):91–2.Krasnyansky V.P., Mikhailov V.V., Borisevich I.V., Gradoboev V.N., Evseev A.A., Pshenichnov V.A. [Production of hyper-immune equine serum against Ebola virus]. Voprosy Virusologii. 1994; 39(2):91–2. (In Russ.)Чепурнов А.А., Мерзликин Н.В., Чепурнова Т.С, Воробьева М.С. Получение кроличьих антисывороток к вирусу Эбола. Вопросы вирусологии. 1994; 39(6):286–8.Chepurnov A.A., Merzlikin N.V., Chepurnova T.S., Vorob’eva M.S. [Production of rabbit anti-sera to Ebola virus]. Voprosy Virusologii. 1994; 39(6):286–8. (In Russ.)Чепурнов А.А., Кудоярова-Зубовичине Н.М., Дедкова Л.М. Разработка методов получения специфических иммуноглобулинов для экстренной профилактики лихорадки Эбола и изучение их свойств. Вестник Российской академии медицинских наук. 1998; 68(4):24–9.Chepurnov A.A., Kudoyarova-Zubovichine N.M., Dedkova L.M. [Development of the methods for specific immunoglobulin production for emergency prophylaxis of Ebola fever and investigation of the immunoglobulin properties]. Bulletin of the Russian Academy of Medical Sciences (Vestnik Rossiiskoi Akademii Meditsinskikh Nauk).1998; 68(4):24–9. (In Russ.)Nakayama E., Saijo M. Animal models for Ebola and Marburg virus infections. Front. Microbiol. 2013; 4:267. DOI: 10.3389/fmicb.2013.00267.Nakayama E., Saijo M. Animal models for Ebola and Marburg virus infections. Front. Microbiol. 2013; 4:267. DOI: 10.3389/fmicb.2013.00267.Marzi A., Banadyga L., Haddock E., Thomas T., Shen K., Horne EJ., Scott D.P., Feldmann H., Ebihara H. A hamster model for Marburg virus infection accurately recapitulates Marburg hemorrhagic fever. Sci. Rep. 2016; 6:39214. DOI: 10.1038/srep39214.Marzi A., Banadyga L., Haddock E., Thomas T., Shen K., Horne EJ., Scott D.P., Feldmann H., Ebihara H. A hamster model for Marburg virus infection accurately recapitulates Marburg hemorrhagic fever. Sci. Rep. 2016; 6:39214. DOI: 10.1038/srep39214.Natesan M., Jensen S.M., Keasey S.L., Kamata T., Kuehne A.I., Stonier S.W., Lutwama J.J., Lobel L., Dye J.M., Ulrich R.G. Human survivors of disease outbreaks caused by Ebola or Marburg virus exhibit cross-reactive and long-lived antibody responses. Clin. Vaccine Immunol. 2016; 23(8):717–24. DOI: 10.1128/CVI.00107-16.Natesan M., Jensen S.M., Keasey S.L., Kamata T., Kuehne A.I., Stonier S.W., Lutwama J.J., Lobel L., Dye J.M., Ulrich R.G. Human survivors of disease outbreaks caused by Ebola or Marburg virus exhibit cross-reactive and long-lived antibody responses. Clin. Vaccine Immunol. 2016; 23(8):717–24. DOI: 10.1128/CVI.00107-16.Hevey M., Negley D., VanderZanden L., Tammariello R.F., Geisbert J., Schmaljohn C., Smith J.F., Jahrling P.B., Schmaljohn A.L. Marburg virus vaccines: comparing classical and new approaches. Vaccine. 2001; 20(3–4):586–93. PubMed PMID: 11672925.Hevey M., Negley D., VanderZanden L., Tammariello R.F., Geisbert J., Schmaljohn C., Smith J.F., Jahrling P.B., Schmaljohn A.L. Marburg virus vaccines: comparing classical and new approaches. Vaccine. 2001;20(3–4):586–93. PubMed PMID: 11672925.Игнатьев Г.М., Агафонов А.П., Стрельцова М.А., Кузьмин В.А. Сравнительное изучение некоторых иммунологических показателей при введении инактивированного вируса марбург морским свинкам. Вопросы вирусологии. 1991; 36(2):421–3.Ignat’ev G.M., Agafonov A.P., Strel’tsova M.A., Kuz’min V.A. [Comparative study of certain immunological features in case of inoculation of guinea pigs with inactivated Marburg virus]. Voprosy Virusologii. 1991; 36(2):421–3. (In Russ.)Ignat’ev G.M., Agafonov A.P., Streltsova M.A., Kashentseva E. A. Inactivated Marburg virus elicits a nonprotective immune response in Rhesus monkeys. J. Biotechnol. 1996; 44(1–3):111–18. DOI: 10.1016/0168-1656(95)00104-2.Ignat’ev G.M., Agafonov A.P., Streltsova M.A., Kashentseva E. A. Inactivated Marburg virus elicits a nonprotective immune response in Rhesus monkeys. J. Biotechnol. 1996; 44(1–3):111–18. DOI: 10.1016/0168-1656(95)00104-2.Grant-Klein R.J., Altamura L.A., Badger C.V., Bounds C.E., VanDeusen N.M., Kwilas S.A., Vu H.A., Warfield K.L., Hooper J.W., Hannaman D., Dupuy L.C., Schmaljohn C.S. Codon-optimized filovirus DNA vaccines delivered by intramuscular electroporation protect cynomolgus macaques from lethal Ebola and Marburg virus challenges. Hum. Vaccin. Immunother. 2015; 11(8):1991–2004. DOI: 10.1080/21645515.2015.1039757.Grant-Klein R.J., Altamura L.A., Badger C.V., Bounds C.E., VanDeusen N.M., Kwilas S.A., Vu H.A., Warfield K.L., Hooper J.W., Hannaman D., Dupuy L.C., Schmaljohn C.S. Codon-optimized filovirus DNA vaccines delivered by intramuscular electroporation protect cynomolgus macaques from lethal Ebola and Marburg virus challenges. Hum. Vaccin. Immunother.2015; 11(8):1991–2004. DOI: 10.1080/21645515.2015.1039757.Riemenschneider J., Garrison A., Geisbert J., Jahrling P., Hevey M., Negley D., Schmaljohna A, Leea J, Harta M. K., Vanderzandena L, Custera D, Braya M, Ruffa A, Ivinsb B, Bassettb A, Rossic C, Schmaljohna C. Comparison of individual and combination DNA vaccines for B. anthracis, Ebola virus, Marburg virus and Venezuelan equine encephalitis virus. Vaccine. 2003; 21(25–26):4071–80. DOI: 10.1016/S0264-410X(03)00362-1.Riemenschneider J., Garrison A., Geisbert J., Jahrling P., Hevey M., Negley D., Schmaljohna A, Leea J, Harta M. K., Vanderzandena L, Custera D, Braya M, Ruffa A, Ivinsb B, Bassettb A, Rossic C, Schmaljohna C. Comparison of individual and combination DNA vaccines for B. anthracis, Ebola virus, Marburg virus and Venezuelan equine encephalitis virus. Vaccine. 2003; 21(25–26):4071–80. DOI: 10.1016/S0264-410X(03)00362-1.Geisbert T. W., Bailey M., Geisbert J. B., Asiedu C., Roederer M., Grazia-Pau M., Custers J, Jahrling P, Goudsmit J, Koup R, Nancy J. Sullivan N.J. Vector choice determines immunogenicity and potency of genetic vaccines against Angola Marburg virus in nonhuman primates. J. Virol.2010; 84(19):10386–94. DOI: 10.1128/JVI.00594-10.Geisbert T. W., Bailey M., Geisbert J. B., Asiedu C., Roederer M., Grazia-Pau M., Custers J, Jahrling P, Goudsmit J, Koup R, Nancy J. Sullivan N.J. Vector choice determines immunogenicity and potency of genetic vaccines against Angola Marburg virus in nonhuman primates. J. Virol. 2010; 84(19):10386–94. DOI: 10.1128/JVI.00594-10.Sarwar U.N., Costner P., Enama M.E., Berkowitz N., Hu Z., Hendel C.S., Sitar S., Plummer S., Mulangu S., Bailer R.T., Koup R.A., Mascola J.R., Nabel G.J., Sullivan N.J., Graham B.S., Ledgerwood J.E; VRC 206 Study Team. Safety and immunogenicity of DNA vaccines encoding Ebolavirus and Marburgvirus wildtype glycoproteins in a phase I clinical trial. J. Infect. Dis. 2015; 211(4):549–57. DOI: 10.1093/infdis/jiu511.Sarwar U.N., Costner P., Enama M.E., Berkowitz N., Hu Z., Hendel C.S., Sitar S., Plummer S., Mulangu S., Bailer R.T., Koup R.A., Mascola J.R., Nabel G.J., Sullivan N.J., Graham B.S., Ledgerwood J.E; VRC 206 Study Team. Safety and immunogenicity of DNA vaccines encoding Ebolavirus and Marburgvirus wildtype glycoproteins in a phase I clinical trial. J. Infect. Dis. 2015; 211(4):549–57. DOI: 10.1093/infdis/jiu511.Kibuuka H., Berkowitz N.M., Millard M., Enama M.E., Tindikahwa A., Sekiziyivu A.B., Costner P., Sitar S., Glover D., Hu Z., Joshi G., Stanley D., Kunchai M., Eller L.A., Bailer R.T., Koup R.A., Nabel G.J., Mascola J.R., Sullivan N.J., Graham B.S., Roederer M., Michael N.L., Robb M.L., Ledgerwood J.E; RV 247 StudyTeam. Safety and immunogenicity of Ebola virus and Marburg virus glycoprotein DNA vaccines assessed separately and concomitantly in healthy Ugandan adults: a phase 1b, randomised, double-blind, placebo-controlled clinical trial. Lancet.2015; 385(9977):1545–54. DOI: 10.1016/S0140-6736(14)62385-0.Kibuuka H., Berkowitz N.M., Millard M., Enama M.E., Tindikahwa A., Sekiziyivu A.B., Costner P., Sitar S., Glover D., Hu Z., Joshi G., Stanley D., Kunchai M., Eller L.A., Bailer R.T., Koup R.A., Nabel G.J., Mascola J.R., Sullivan N.J., Graham B.S., Roederer M., Michael N.L., Robb M.L., Ledgerwood J.E; RV 247 StudyTeam. Safety and immunogenicity of Ebola virus and Marburg virus glycoprotein DNA vaccines assessed separately and concomitantly in healthy Ugandan adults: a phase 1b, randomised, double-blind, placebo-controlled clinical trial. Lancet.2015; 385(9977):1545–54. DOI: 10.1016/S0140-6736(14)62385-0.Milligan I.D., Gibani M.M., Sewell R., Clutterbuck E.A., Campbell D., Plested E., Nuthall E., Voysey M., Silva-Reyes L., Mc Elrath M.J., DeRosa S.C., Frahm N., Cohen K.W., Shukarev G., Orzabal N., van Duijnhoven W., Truyers C., Bachmayer N., Splinter D., Samy N., Pau M.G., Schuitemaker H., Luhn K., Callendret B., Van Hoof J., Douoguih M., Ewer K., Angus B., Pollard A.J., Snape M.D. Safety and immunogenicity of novel adenovirus type 26- and modified vaccinia Ankara-vectored Ebola vaccines: a randomized clinical trial. JAMA. 2016; 315(15):1610–23. DOI: 10.1001/jama.2016.4218.Milligan I.D.,Gibani M.M., Sewell R., Clutterbuck E.A., Campbell D., Plested E., Nuthall E., Voysey M., Silva-Reyes L., Mc Elrath M.J., DeRosa S.C., Frahm N., Cohen K.W., Shukarev G., Orzabal N., van Duijnhoven W., Truyers C., Bachmayer N., Splinter D., Samy N., Pau M.G., Schuitemaker H., Luhn K., Callendret B., Van Hoof J., Douoguih M., Ewer K., Angus B., Pollard A.J., Snape M.D. Safety and immunogenicity of novel adenovirus type 26- and modified vaccinia Ankara-vectored Ebola vaccines: a randomized clinical trial. JAMA. 2016; 315(15):1610–23. DOI: 10.1001/jama.2016.4218.Dolzhikova I.V., Tokarskaya E.A., Dzharullaeva A.S., Tukhvatulin A.I., Shcheblyakov D.V., Voronina O.L., Syromyatnikova S.I., Borisevich S.V., Pantyukhov V.B., Babira V.F., Kolobukhina L.V., Naroditsky B.S., Logunov D.Y., Gintsburg A. L. Virus-vectored Ebola vaccines. Acta Naturae.2017; 9 (3):4–12.Dolzhikova I.V., Tokarskaya E.A., Dzharullaeva A.S., Tukhvatulin A.I., Shcheblyakov D.V., Voronina O.L., Syromyatnikova S.I., Borisevich S.V., Pantyukhov V.B., Babira V.F., Kolobukhina L.V., Naroditsky B.S., Logunov D.Y., Gintsburg A. L. Virus-vectored Ebola vaccines. Acta Naturae.2017; 9 (3):4–12.Li J.X., Hou L.H.,Meng F.Y., Wu S.P., Hu Y.M., Liang Q., Chu K., Zhang Z., Xu J.J., Tang R., Wang W.J., Liu P, Hu J.L., Luo L., Jiang R., Zhu F.C., Chen W. Immunity duration of a recombinant adenovirus type-5 vector-based Ebola vaccine and a homologous prime-boost immunisation in healthy adults in China: final report of a randomised, double-blind, placebo-controlled, phase 1 trial. Lancet Glob. Health. 2017; 5(3):e324–e334. DOI: 10.1016/S2214-109X (16)30367-9.Li J.X., Hou L.H., Meng F.Y., Wu S.P., Hu Y.M., Liang Q., Chu K., Zhang Z., Xu J.J., Tang R., Wang W.J., Liu P, Hu J.L., Luo L., Jiang R., Zhu F.C., Chen W. Immunity duration of a recombinant adenovirus type-5 vector-based Ebola vaccine and a homologous prime-boost immunisation in healthy adults in China: final report of a randomised, double-blind, placebo-controlled, phase 1 trial. Lancet Glob. Health. 2017; 5(3):e324–e334. DOI: 10.1016/S2214-109X (16)30367-9.Coller B.G.,Blue J., Das R., Dubey S., Finelli L., Gupta S., Helmond F., Grant-Klein R.J., Liu K., Simon J., Troth S., Van Rheenen S., Waterbury J., Wivel A., Wolf J., Heppner D.G., Kemp T., Nichols R., Monath T.P. Clinical development of a recombinant Ebola vaccine in the midst of an unprecedented epidemic. Vaccine. 2017; 35(35 Pt A):4465–4469. DOI: 10.1016/j.vaccine.2017.05.097.Coller B.G., Blue J., Das R., Dubey S., Finelli L., Gupta S., Helmond F., Grant-Klein R.J., Liu K., Simon J., Troth S., Van Rheenen S., Waterbury J., Wivel A., Wolf J., Heppner D.G., Kemp T., Nichols R., Monath T.P. Clinical development of a recombinant Ebola vaccine in the midst of an unprecedented epidemic. Vaccine. 2017; 35(35 Pt A):4465–4469. DOI: 10.1016/j.vaccine.2017.05.097.Geisbert T.W., Geisbert J.B., Leung A., Daddario-Dicaprio K.M., Hensley L.E., Grolla A., Feldmann H. Single-injection vaccine protects nonhuman primates against infection with Marburg virus and three species of Ebola virus. J. Virol.2009; 83(14):7296–304. DOI: 10.1128/JVI.00561-09.Geisbert T.W., Geisbert J.B., Leung A., Daddario-Dicaprio K.M., Hensley L.E., Grolla A., Feldmann H. Single-injection vaccine protects nonhuman primates against infection with Marburg virus and three species of Ebola virus. J. Virol. 2009; 83(14):7296–304. DOI: 10.1128/JVI.00561-09.Noda T., Sagara H., Suzuki E., Takada A, Kida H., Kawaoka Y. Ebola virus VP40 drives the formation of virus-like filamentous particles along with GP. J. Virol. 2002; 76(10):4855–65. PubMed PMID: 11967302.Noda T., Sagara H., Suzuki E., Takada A, Kida H., Kawaoka Y. Ebola virus VP40 drives the formation of virus-like filamentous particles along with GP. J. Virol. 2002; 76(10):4855–65. PubMed PMID: 11967302.Licata J., Johnson R.F., Han Z. Harty R.N. Contribution of Ebola virus glycoprotein, nucleoprotein, and VP24 to budding of VP40 virus-like particles. J. Virol.2004; 78(14):7344–51. DOI: 10.1128/JVI.78.14.7344-7351.2004.Licata J., Johnson R.F., Han Z. Harty R.N. Contribution of Ebola virus glycoprotein, nucleoprotein, and VP24 to budding of VP40 virus-like particles. J. Virol. 2004; 78(14):7344–51. DOI: 10.1128/JVI.78.14.7344-7351.2004.Swenson D.L., Warfield K.L., Larsen T., Alves D.A., Coberley S.S., Bavari S. Monovalent virus-like particle vaccine protects guinea pigs and nonhuman primates against infection with multiple Marburg viruses. Expert. Rev. Vaccines.2008; 7(4):417–29. DOI: 10.1586/14760584.7.4.417.Swenson D.L., Warfield K.L., Larsen T., Alves D.A., Coberley S.S., Bavari S. Monovalent virus-like particle vaccine protects guinea pigs and nonhuman primates against infection with multiple Marburg viruses. Expert. Rev. Vaccines. 2008; 7(4):417–29. DOI: 10.1586/14760584.7.4.417.Dye J.M., Warfield K.L., Wells J.B., Unfer R.C., Shulenin S., Vu H., Nichols D.K., Aman M.J., Bavari S. Virus-Like Particle Vaccination Protects Nonhuman Primates from Lethal Aerosol Exposure with Marburgvirus (VLP Vaccination Protects Macaques against Aerosol Challenges). Viruses.2016; 8(4):94. DOI: 10.3390/v8040094Dye J.M.,Warfield K.L., Wells J.B., Unfer R.C., Shulenin S., Vu H., Nichols D.K., Aman M.J., Bavari S. Virus-Like Particle Vaccination Protects Nonhuman Primates from Lethal Aerosol Exposure with Marburgvirus (VLP Vaccination Protects Macaques against Aerosol Challenges). Viruses. 2016; 8(4):94. DOI: 10.3390/v8040094

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