epidemiologyЭпидемиология и ВакцинопрофилактикаEpidemiology and Vaccinal Prevention2073-30462619-0494«Numicom» LLC10.31631/2073-3046-2016-15-4-74-82epidemiology-185Research ArticleВАКЦИНОПРОФИЛАКТИКАVACCINAL PREVENTIONСостояние и перспективы разработки вакцин для специфической профилактики энтеровирусной (неполио) инфекцииCondition and Prospects of Development of Vaccines for Specific Prevention of Enterovirus (Nonpolio) InfectionЯговкинЭ. А.YagovkinE. A.noemail@neicon.ruОнищенкоГ. Г.OnishchenkoG. G.noemail@neicon.ruПоповаА. Ю.PopovaA. Yu.noemail@neicon.ruЕжловаЕ. Б.EzhlovaE. B.noemail@neicon.ruМельниковаА. А.MelnikovaA. A.noemail@neicon.ruСоловьевМ. Ю.SolovievM. Yu.noemail@neicon.ruКовалевЕ. В.KovalevE. V.noemail@neicon.ruТвердохлебоваТ. И.TverdokhlebovaT. I.noemail@neicon.ruХмелевскаяГ. В.KhmelevskayaG. V.noemail@neicon.ruДевтероваЛ. В.DevterovaL. V.noemail@neicon.ruВачаевБ. Ф.VachaevB. F.noemail@neicon.ruЮрьеваИ. Л.YuryevaI. L.noemail@neicon.ruФБУН «Ростовский НИИ микробиологии и паразитологии» РоспотребнадзораRussian FederationРоссийская академия наукRussian FederationРоспотребнадзорRussian FederationУправление Роспотребнадзора по Ростовской областиRussian Federation2016200820161547482Copyright © Яговкин Э.А., Онищенко Г.Г., Попова А.Ю., Ежлова Е.Б., Мельникова А.А., Соловьев М.Ю., Ковалев Е.В., Твердохлебова Т.И., Хмелевская Г.В., Девтерова Л.В., Вачаев Б.Ф., Юрьева И.Л., 20162016Яговкин Э.А., Онищенко Г.Г., Попова А.Ю., Ежлова Е.Б., Мельникова А.А., Соловьев М.Ю., Ковалев Е.В., Твердохлебова Т.И., Хмелевская Г.В., Девтерова Л.В., Вачаев Б.Ф., Юрьева И.Л.Yagovkin E.A., Onishchenko G.G., Popova A.Y., Ezhlova E.B., Melnikova A.A., Soloviev M.Y., Kovalev E.V., Tverdokhlebova T.I., Khmelevskaya G.V., Devterova L.V., Vachaev B.F., Yuryeva I.L.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://www.epidemvac.ru/jour/article/view/185

В обзоре обобщены материалы исследований по разработке вакцин против (неполио) энтеровирусной инфекции в России и за рубежом. Описаны разрабатываемые виды вакцин, их характеристики и результаты клинико-эпидемиологических испытаний, созданных в Китае инактивированных вакцин. Рассматриваются возможность создания мукозальных вакцин и стратегия вакцинопрофилактики.

This review summarizes the material on the development of vaccines against (nonpolio) enterovirus infection in Russia and abroad. Described the developed vaccine types, their characteristics and the results of clinical and epidemiological trials, created in China inactivated vaccines. I’is considered the possibility of creating a mucosal vaccines and vaccinal prevention strategies.

(неполио) энтеровирусная инфекциявакцинавакцинопрофилактика(nonpolio) enterovirus infectionvaccinevaccinal preventionReferencesОнищенко Г.Г., Ежлова Е.Б., Мельникова А.А. Актуальные вопросы организации вакцинопрофилактики в Российской Федерации. Микробиол. 2011; 5: 110 - 114.Onishchenko G.G., Ezhlova E.B., Mel'nikova A.A. Actual problems of vaktsinoprofilaktika in the Russian Federation. Journal Mikrobiologii [Journal Microbiology]. 2011; 5: 110 – 114 (in Russian).http://www.polioeradication.org/Portals/0/Document/Resources/StrategyWork/PEESP_ES_RUS_A4.pdfhttp://www.polioeradication.org/Portals/0/Document/Resources/StrategyWork/PEESP_ES_RUS_A4.pdfСейбиль В.В., Малышкина Л.П. Энтеровирусы в ХХ - XXI веках. Микробиол. 2005; 4: 83 - 89.Seybil V.V., Malyshkina L.P. Enteroviruses in XX – XXI centuries. Journal Mikrobiologii [Journal Microbiology]. 2005; 4: 83 – 89 (in Russian).Яшкулов К.Б., Шевырева М.Н., Лазикова Г.Ф., Ясинский А.А., Котова Г.А., Чимидова Р.И. Вспышка энтеровирусной инфекции с серозным менингитом в Республике Калмыкия и меры по ее локализации и ликвидации. Здоровье населения и среда обитания. 2003; 5 (122): 12 - 18.Yashkulov K.B., Shevyreva M.N., Lazikova G.F., Jasinsky A.A., Kotova G.A., Chimidova R.I. The outbreak of enterovirus infections with serous meningitis in the Republic of Kalmykia and measures for its localization and liquidation. Zdravoohranenie i sreda obitania [Public health and environment habitat]. 2003; 5 (122): 12 – 18 (in Russian).Shindarov J., Chumakov M.P., Voroshilova M.K. et al. Epidemiological, clinical and pathomorphological characteristics of epidemic poliomyelitis like disease caused by enterovirus 71. J. Hug. Epidemiol. Microbio. 1979; 23: 284 - 295.Shindarov J., Chumakov M.P., Voroshilova M.K. Bojinov S., Vasilenko S.M., Iordanov I. et al. Epidemiological, clinical and pathomorphological characteristics f epidemic poliomyelitis like disease caused by enterovirus 71. J. Hyg. Epidemiol. Microbio.1979; 23: 284 – 295В.И. Покровский. Инфекционные болезни и эпидемиология; 2007.Pokrovsky V.I. Infectious diseases and epidemiology; 2007 (in Russian).Ворошилова М.К. Энтеровирусные инфекции человека. Москва; 1970: 295 - 340.Voroshilova M.K. Human enterovirus infection. Moscow; 1970: 295 – 340 (in Russian).Zhang D., Lu Yi., Lu Yi. Enterovirus 71 vaccine: close but still far. International Journal of Infection Diseases. 2010; 14: 749 - 743.Zhang D., Lu Yi., Lu Yi. Enterovirus 71 vaccine: close but still far. International Journal of Infection Diseases. 2010; 14: 749 – 743.Yu C.K., Chen C.C., Chen C.L., Wang J.R., Liu C.C., Yan J.J. et al. Neutralizing antibody provide protection against enterovirus type 71 lethal challenge in neonatal mice. J. Biomed Sei. 2000;7: 523 - 528.Yu C.K., Chen C.C., Chen C.L., Wang J.R., Liu C.C., Yan J.J. et al. Neutralizing antibody provide protection against enterovirus type 71 lethal challenge in neonatal mice. J. Biomed Sei. 2000;7: 523 – 528.Lin Y.C., Wu C.N., Shin S.R., Ho M.S. Characterization of a vero-cell adapter virulent strain of enterovirus 71 suitable for use a vaccine candidate. Vaccine. 2002; 20: 2485 - 2495.Lin Y.C., Wu C.N., Shin S.R., Ho M.S. Characterization of a vero-cell adapter virulent strain of enterovirus 71 suitable for use a vaccine candidate. Vaccine. 2002; 20: 2485 – 2495.Wu S.C., Liu C.C., Lian W.C. Optimization of micro carrier cell process for the inactivated entorovirus type 71 vaccine development. Vaccine. 2004; 22: 3858 - 3964.Wu S.C., Liu C.C., Lian W.C. Optimization of micro carrier cell process for the inactivated entorovirus type 71 vaccine development. Vaccine. 2004; 22: 3858 – 3964.Liu C.C., Liun W.C., Butler M., Wu S.C. High immunogenic enterovirus 71 strain and its production using serum-free micro carrier vero-cell culture. Vaccine. 2007; 25: 19 - 24.Liu C.C., Liun W.C., Butler M., Wu S.C. High immunogenic enterovirus 71 strain and its production using serum-free micro carrier vero-cell culture. Vaccine. 2007; 25: 19 – 24.Arita M., Ami Y., Wakita T., Shimizu H., Cooperative effect of the attenuation determinants derived from poliovirus Sabine 1 strain is essential for attenuation of enterovirus 71 in the NOD/SCID mouse infection model. J. Virol. 2007: 9386 - 9395.Arita M., Ami Y., Wakita T., Shimizu H., Cooperative effect of the attenuation determinants derived from poliovirus Sabine 1 strain is essential for attenuation of enterovirus 71 in the NOD/SCID mouse infection model. J. Virol. 2007: 9386 – 9395.Arita M., Shimizu H., Nagata N., Ami Y., Suzaki Y., Sata et al. Temperature sensitive mutants of enterovirus monkeys. J. Gen. Virol. 2005; 86: 391 - 1401.Arita M., Shimizu H., Nagata N., Ami Y.,Suzaki Y.,Sata et al.. Temperature sensitive mutants of enterovirus monkeys. J. Gen. Virol. 2005; 86: 391 – 1401.Arita M., Nagata N., Iwata N., Ami Y., Suzaki Y., Mizuta K. et al. An attenuated strain of enterovirus 71 belonging to genotype A showed a broud spectrum of antigencity with attenuated neurovirulence in cynomolgus monkey. J. Virol. 2007; 81: 9386 - 9395.Arita M., Nagata N., Iwata N., Ami Y., Suzaki Y., Mizuta K. et al.. Аn attenuated strain of enterovirus 71 belonging to genotype A showed a broud spectrum of antigencity with attenuated neurovirulence in cynomolgus monkey. J. Virol. 2007; 81: 9386 – 9395.Wu C.N., Lin Y.C., Fanu C., Liao N.S., Shih S.R., Ho M.S. Protection against lethal enterovirus 71 infection in newborn mice by passive immunization with subunit VP1 vaccine and inactivated virus. Vaccine. 2001; 20: 3858 - 3864.Wu C.N., Lin Y.C., Fanu C., Liao N.S., Shih S.R., Ho M.S. Protection against lethal enterovirus 71 infection in newborn mice by passive immunization with subunit VP1 vaccine and inactivated virus. Vaccine. 2001; 20: 3858 – 3864.Xu L., He D., Li Zh., Zheng J., Yang L., Yu M. et al. Protection against lethal enterovirus 71 chellenger in mice by recombinant vaccine Candidate containing a Broadly Cross-neutralizing epitope with the VP EF Loop. Theranostics. 2014; 4 (5): 498 - 502.Xu L., He D., Li Zh., Zheng J., Yang L., Yu M. et al.. Protection against lethal enterovirus 71 chellenger in mice by recombinant vaccine Candidate containing a Broadly Cross-neutralizing epitope with the VP EF Loop. Theranostics. 2014; 4 (5): 498 – 502.Negiected Tropical Disease/ DOI:10.1371/Journal pntd 0003692 April 9.2015: 1/22-21/22.Negiected Tropical Disease/ DOI:10.1371/Journal pntd 0003692 April 9.2015: 1/22-21/22.Chen H.F., Chang M.H., Chiang B.L., Jeng S.T. Oral immunization of mice using transgenic tomato fruit expressing VP1 protein from enterovirus 71. Vaccine. 2006; 24: 2944 - 2951.Chen H.F., Chang M.H., Chiang B.L., Jeng S.T. Oral immunization of mice using transgenic tomato fruit expressing VP1 protein from enterovirus 71. Vaccine. 2006; 24: 2944 – 2951.Chen H.L., Huang J.J., Chu T.W., Tsai T.C., Huang C.M., Lin C.C. et al. Expression of VP1 protein in the milk of transgenic mice a potential oral vaccine protects against enterovirus 71 infection. Vaccine. 2008; 26: 2882 - 2889.Chen H.L., Huang J.J., Chu T.W., Tsai T.C., Huang C.M., Lin C.C. et al.. Expression of VP1 protein in the milk of transgenic mice a potential oral vaccine protects against enterovirus 71 infection. Vaccine. 2008; 26: 2882 – 2889.Семенов Б.Ф., Зверев В.В., Хаитов РМ., Вакцинопрофилактика в XXI веке: настоящее и будущее. Иммунология. 2009; 30 (6): 324 - 335.Semenov B.F., Zverev V.V., Haitov R.M. Vaccine Prevention in the twenty-first century: the present and the future. Immunology. 2009; 30 (6): 324 – 335 (in Russian).Tung W.S., Bakaz S.A., Sekawi Z., Rosli R. DMA vaccinec constructs against enterovirus 71 elicit immune response in mice. Genet. Vaccines Ther. 2007; 5: 7.Tung W.S., Bakaz S.A., Sekawi Z., Rosli R. DMA vaccinec constructs against enterovirus 71 elicit immune response in mice. Genet Vaccines Ther. 2007; 5: 7.Wu C.N., Lin Y.C., Fanu C., Liao N.S., Shih S.R., Ho M.S. Protection against lethal enterovirus 71 infection in newborn mice by passive immunization with subunit VP1 vaccine and inactivated virus. Vaccine. 2001; 20: 3858 - 3864.Wu C.N., Lin Y.C., Fanu C., Liao N.S., Shih S.R., Ho M.S. Protection against lethal enterovirus 71 infection in newborn mice by passive immunization with subunit VP1 vaccine and inactivated virus. Vaccine. 2001; 20: 3858 – 3864.Foo D.G., Macary PA., Alonso S., Poh C.P Identification of human CD4 T-cell epitopes on the VP1 capsid protein of enterovirus 71. Virol immunal. 2008; 21: 213 - 224.Foo D.G., Macary P.A., Alonso S., Poh C.P. Identification of human CD4 T-cell epitopes on the VP1 capsid protein of enterovirus 71. Virol immunal. 2008; 21: 213 – 224.Foo D.G., Alonso S., Phoon M.C., Ramachandran N.P, Chow V.T., Pon C.L. Identification of neutralizing liner epitopes from VP capsid protein of enterovirus 71 using syntetic peptides. Virus Res. 2007; 125: 61 - 68.Foo D.G., Macary P.A., Alonso S., Poh C.P. Identification of human CD4 T-cell epitopes on the VP1 capsid protein of enterovirus 71. Virol immunal. 2008; 21: 213 – 224.Foo D.G., Alonso S., Chow V.T., Poh C.L. Passive protection against lethal enterovirus 71 infection in newborn mice by neutralizing elicited by syntetic peptide. Microbes Infect. 2007; 9: 1299 - 1306.Foo D.G., Alonso S., Chow V.T., Poh C.L. Passive protection against lethal enterovirus 71 infection in newborn mice by neutralizing elicited by syntetic peptide. Microbes Infect. 2007; 9: 1299 – 1306.Li Y.-X., Zhao H., Cao R.-Y., Deng Y.-Q., Han J.-F., Zhu Sh.-Ya. et al. Recombinant tandem multi-linear neutralizing epitopes of human enterovirus 71 elicited protective immunity in mice. Virology Journal. 2014; 11 (79): 2 - 8. Доступно на: http//www.virologycom/content /ll/1/79.Li Y.-X., Zhao H., Cao R.-Y., Deng Y.-Q., Han J.-F., Zhu Sh.-Ya. et al. et al. Recombinant tandem multi-linear neutralizing epitopes of human enterovirus 71 elicited protective immunity in mice. Virology Journal. 2014;11 (79): 2 – 8. Available at: http//www.virologycom/content /ll/1/79.Карпенко Л.И., Бажан С.И., Ужаченко РІВ., Некрасова Н.А., Лебедев Л.Р., Агафонов А.В. и др. Различные формы кандидатных вакцин против ВИЧ-1, несущих полиэпитопные иммуногены. Биопрепараты. 20064; 4: 8 - 10.Karpenko L.I., Bajan S.I., Uzhachenko R.V., Nekrasova N.A., Lebedev L.R., Agafonov A.V. et al. Various forms of candidate vaccines against HIV-1 bearing polyepitope immunogens. Biopreparati [Biodrugs]. 2006; 4: 8 – 10 (in Russian).Hu Y.C., Hsu J.T., Huang J.H., Ho M.S., Ho Y.C. Formation of enterovirus-like particle aggregates by recombinant baculoviruses co-expressing P1 and 3CD in insect cells. Biotechnol Lett. 2003; 25: 919 - 925Hu Y.C., Hsu J.T., Huang J.H., Ho M.S., Ho Y.C. Formation of enterovirus-like particle aggregates by recombinant baculoviruses co-expressing P1 and 3CD in insect cells. Biotechnol Lett. 2003; 25: 919 – 925.Chung Y.C., Ho M.S., Wu J.C., Chen W.J., Huang J.H., Chou S.T. et al. Immunization with virus-like particies of enterovirus 71 elicits potent immune responses and protect mice against lethal challenge. Vaccine. 2008; 26: 1855 - 1862.Chung Y.C., Ho M.S., Wu J.C., Chen W.J., Huang J.H., Chou S.T. et al. Immunization with virus-like particies of enterovirus 71 elicits potent immune responses and protect mice against lethal challenge. Vaccine. 2008; 26: 1855 – 1862.Tsou Y.-L., Lin Yi.-W., Shao H.-Yu., Yu Sh.-L., Wu Sh.-R., Lin H.-Yu. et al. Recombinant Adeno-vaccine expression enterovirus 71-like particles against Hand, Foot and Mouse Disease. PLOS Negiected Tropical Disease/ DOI:10.1371/Journal pntd 0003692 April 9.2015: 1/22-21/22Tsou Y.-L., Lin Yi.-W., Shao H.-Yu., Yu Sh.-L., Wu Sh.-R., Lin H.-Yu. et al. Recombinant Adeno-vaccine expression enterovirus 71-like particles against Hand, Foot and Mouse Disease. PLOS Negiected Tropical Disease/ DOI:10.1371/Journal pntd 0003692 April 9.2015:1/22-21/22.Zhao H., Li H.-Ya., Han Ji.-F., Deng Yo.-Q., Zhu Sh.-Ya., Li X.-F. et al. Novel recombinant chimeric virus-like particle is immunogenic and protective against bother enterovirus 71 coxsackievirus A16 in mice. Scientific Reports [5:7878] DOI:10.1038/s 07878 Pub 19 January 2015: 1 - 7.Zhao H., Li H.-Ya., Han Ji.-F., Deng Yo.-Q., Zhu Sh.-Ya., Li X.-F. et al. Novel recombinant chimeric virus-like particle is immunogenic and protective against bother enterovirus 71 coxsackievirus A16 in mice. Scientific Reports [5:7878] DOI:10.1038/s 07878 Pub 19 January 2015: 1 – 7.Lin Yu.-L., Hu Yu.-Ch., Lian Ch.-Ch., Lin Sh.-Ye., Liang Yu.-Ch., Yuan H.P et al. Enterovirus-like particles induce the activation and maturation of human monocyte-derived dendric cells throught TLR4 signaling. Plos one/www.plosone. orgOctober 2014/volume 9/issue 10/e111u96: 1 - 11.Lin Yu.-L., Hu Yu.-Ch., Lian Ch.-Ch., Lin Sh.-Ye., Liang Yu.-Ch., Yuan H.P. et al. Enterovirus-like particles induce the activation and maturation of human monocyte-derived dendric cells throught TLR4 signaling. Plos one/www.plosone.orgOctober 2014/volume 9/issue 10/e111u96: 1 – 11.Chai O.K., Shamala D., Jam C.M., Thong W.K. Formaldehyde-inactivated whole -virus vaccine Protects a Murine Model of enterovirus 71 Encephalomyelitis against Disease. Journal of virology. 2010; January: 661 - 665.Chai O.K., Shamala D., Jam C.M., Thong W.K. Formaldehyde-inactivated whole –virus vaccine Protects a Murine Model of enterovirus 71 Encephalomyelitis against Disease. Journal of virology. 2010; January: 661 – 665.Chou Ai.-H., Liu Ch.-Ch., Chang Gh.-Peng., Guo M.-Sh., Hsieh Sh.-Yu., Yung W.-H. et al. Pilot scale production of Highly efficacious and stable enterovirus 71 vaccine candidates. Plos one www.plosone.org 2012; v7. April: 1 - 9.Chou Ai.-H., Liu Ch.-Ch., Chang Gh.-Peng., Guo M.-Sh., Hsieh Sh.-Yu., Yung W.-H. et al. Pilot scale production of Highly efficacious and stable enterovirus 71 vaccine candidates. Plos one www.plosone.org 2012; v7.April: 1 – 9.Hwu Shi-H., Lu Y.A., Brewoo J., Partidos C.D., Osorio J.E., Santangelo J.D. Preclinic evolution of the Immunogenecity and Safety of an Inactivated Enterovirus 71 candidate vaccine. Plos Neglected Tropical Diseases www.plosntds.org 2013; 7: 1 - 7.Hwu Shi-H., Lu Y.A., Brewoo J., Partidos C.D., Osorio J.E., Santangelo J.D. Preclinic evolution of the Immunogenecity and Safety of an Inactivated Enterovirus 71 candidate vaccine. Plos Neglected Tropical Diseases www.plosntds.org 2013; 7: 1 – 7.Liu Ch-Ch., Hwang Ch-S., Yang W.-S., Tsai D.-Ch., Wu S.-H., Chou A.-H. et al. Long-Term immunogenecity studies of formalin-inactivated enterovirus 71 whole-virion vaccine in macaques. Plos one www.plosone.org. 2014; September. vol. 9 issue: 1 - 5.Liu Ch.-Ch., Hwang Ch.-S., Yang W.-S., Tsai D.-Ch., Wu S.-H., Chou A.-H. et al. Long-Term immunogenecity studies of formalin-inactivated enterovirus 71 whole-virion vaccine in macaques. Plos one www.plos one.org. 2014; 9: 1 – 5.Li L, Yin H, An Z, Feng Z. Consideration for developing an I strategy with mmunization enterovirus 71 vaccine. Vaccine. 2015; 33: 1107 - 1112.Li L., Yin H., An Z., Feng Z. Consideration for developing an I strategy with mmunization enterovirus 71 vaccine. Vaccine. 2015; 33: 1107 – 1112.Zhu F.C., Meng F.Y., Li J.X., Mao Q.Y., Tao H. et al. Efficacy, safety, and immunology of an inactivated alum-adjuvant enterovirus 71 vaccine in children in Chine: a multicentre, randomized, double-blind, placebo-controlled phase 3 trial. Lancet 2013; 381: 2024 - 2032.Zhu F.C., Meng F.Y., Li J.X., Mao Q.Y., Tao H. et al. Efficacy, safety, and immunology of an inactivated alum-adjuvant enterovirus 71 vaccine in children in Chine: a multicentre, randomized, double-blind, placebo-controlled phase 3 trial. Lancet. 2013; 381: 2024 – 2032.Хаитов Р.М., Пинегин Б.В., Ярилин A.A. Руководство по клинической иммунологии. Диагностика заболеваний иммунной системы: руководство для врачей. Медицина. 2009: 345.Haitov R.M., Pinegin B.V., Yarilin A.A. Manual of clinical immunology. Diagnosis of diseases of the immune system: a manual for doctors. Medicine. 2009: 345 (in Russian).Бацкалевич Н.А. Клинические, иммунологические особенности и прогностическая оценка показателей врожденного и адаптивного иммунитета у подростков с энтеровирусным менингитом: Дис.. канд. мед. наук. Екатеринбург; 2009: 130.Batskalevich N.A. Clinical, immunological characteristics and prognostic avalution of indicators of innate and adaptive immunity in adolescents with enteroviruses meningitis. Doctorate of med. sci. diss. Ekaterinburg; 2009: 130 (in Russian).Фомин В.В., Чеснокова О.А., Ерман Б.А., Биткин Я.Б. Энтеровирусные инфекции у детей. Екатеринбург; 1991: 38 - 98.Fomin V.V., Chesnokova O.A., Erman B.A., Bitkin I.B. Enterovirus infection in children. Ekaterinburg; 1991: 38 – 98 (in Russian).Shuangsuo D., Niig G., Yaping L., Mei L., Xiufang W., Xiaoli J. et al. Dominant CD4-dependent RNA-dependent RNA polymerase - specific T-cell responses in children acutely infected with human enterovirus 71 and healthy adult controls. Immunology. 2013; 142: 89 - 100.Shuangsuo D., Niig G., Yaping L., Mei L., Xiufang W., Xiaoli J. et al. Dominant CD4-dependent RNA-dependent RNA polymerase – specific T-cell responses in children acutely infected with human enterovirus 71 and healthy adult controls. Immunology. 2013; 142: 89 – 100.Blanchard-Rohner G., Pollard A.J. Long-term protection after immunization with protein - polysaccharide conjugate vaccine in infancy. Rev.Vaccines-2011; 10 (5): 673-684/dol:10.1586/erv.11.14Blanchard-Rohner G., Pollard A.J. Long-term protection after immunization with protein – polysaccharide conjugate vaccine in infancy. Rev. Vaccines-2011; 10 (5): 673 – 684/dol:10.1586/erv.11.14.Вачаев Б.Ф. Яговкин Э.А., Онищенко Г.Г., Медуницин Н.В., Шепиков А.Л., Юрьева И.Л., Головина С.В., и др. Состояние и перспективы разработки отечественной вакцины против гемофильной инфекции. Эпидемиология и инфекционные болезни. 2005; 3: 37 - 39.Vachaev B.F., Yagovkin E.A., Onishchenko G.G., Medunitsin N.V., Shepikov A.L., Yaryeva I.L. et al. The state and prospects the development of the domestic vaccine against Haemophilus influenzae type b infection. Epidemiologia i infekcionnoje bolezni.[Epidemiology and infectious diseases]. 2005; 3: 37 – 39 (in Russian).Павлова Л.И., Вачаев Б.Ф., Русакова Л.А., Горбунова М.А., Яговкин Э.А., Чупринина РЛ., Немировская Т.И. и др. Результаты клинических испытаний отечественной вакцины против гемофильной тип в инфекции. Биопрепараты. 2007; 4 (28): 12 - 15.Pavlova L.I., Vachaev B.F., Rusakova L.A., Gorbunova M.A., Yagovkin E.A., Chuprinina R.L., Nemirovskaya T.I. and et al. The results of clinical trials of a vaccine against Haemophilus influenzae type b infection. Biopreparati [Biodrugs]. 2007; 4 (28): 12 – 15.Вачаев Б.Ф., Юрьева И.П., Яговкин Э.А. и др. Разработка отечественной вакцины против гемофильной тип в инфекции. Актуальные вопросы инфекционной патологии сб. докладов юбилейной научно-практической конференции, посвященной 100 летию Ростовского НИИ микробиологии и паразитологии 23 - 24 сентября 2004 г. Ростов-на-Дону. 2004: 247 - 251.Vachaev B.F., Yaryeva I.L., Yagovkin E.A. et al. Development of domestic vaccine against Haemophilus influenzae type in infection. Actual problems of infectious pathology coll. reports jubilee scientific and practical conference dedicated to the 100th anniversary of the Rostov Research Institute of Microbiology and Parasitology, 23 – 24 September 2004 Rostov-on-Don: 247 – 251 (in Russian).Колесников А.В., Козырев А.В., Шемякин С.А., Дятлов И.А. Современные представления о механизме активации иммунного ответа конъюгированными полисахарными вакцинами. Журнал микробиологии. 2015; 3: 97 - 106..Kolesnikov A.V., Kozyrev AV, Shemyakin S.A., Dyatlov I.A. Modern ideas about the mechanism of activation of the immune response polisaharide conjugated vaccines. Jurnal mikrobiologii [Journal Microbiology]. 2015; 3: 97 – 106.Баринская И.Ф., Ляшенко В.А., Алимбарова Л.М., Лазаренко A.A., Сергеев О.В. Экспериментальные подходы к разработке мукозальных вакцин при вирусных заболеваниях, передающихся половым путем. Иммунология. 2013; 34 (2): 119 - 122.Barinskaja I.F., Lyashenko V.A., Alimbarova L.M., Lazarenko A.A., Sergeev O.V. Experimental approaches to the development of mucosal vaccines for viral diseases, sexually transmitted. Immunologia [Immunology[. 2013; 34 (2): 119 – 122 (in Russian).Караулов А.В., Алешкин В.А., Воропаева Е.А., Метельская В.А., Слободенюк В.В., Афанасьев М.С. и др. Показатели колонизационной резистентности слизистых ротоглотки как объективные критерии мукозального иммунитета при бронхитах у детей. Иммунология. 2012; 33 (5): 255 - 259.Karaulov A.V., Aleshkin V.A., Voropaeva E.A., Metelskaya V.A., Slobodenyuk V.V. Afanasiev M.S. et al. Indicators mucous oropharyngeal colonization resistance as the objective criteria of mucosal immunity in case of bronchitis in children. Immunologia [Immunology]. 2012; 33 (95): 255 – 259 (in Russian).Zhang F., Hao Ch., Zhang Sh., Li I., Zhang Q., Wu W., Liu L., Li Ch. et al. Oral immunization with recombinant enterovirus 71VP1 formulated with chitosan protects mice against lethal challenge. Virology Journal.2014; 11(80): 3 - 9. Доступно на: http://wwwvirology.eom/content/11/1/80Zhang Fushun., Hao Chunsheng., Zhang Shuo., Li Iqian., Zhang Quanfu., Wu Wei. et al. Oral immunization with recombinant enterovirus 71VP1 formulated with chitosan protects mice against lethal challenge. Virology Journal 2014; 11 (80): 3 – 9. Аvailable at: http://wwwvirology.com/content/11/1/80.

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