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Вопросы вирусологии. 2015; 60: 44-49

Испытание апатогенного вируса гриппа H5N3 в качестве живой ветеринарной вакцины

Боравлева Е. Ю., Чвала И. А., Ломакина Н. Ф., Репин П. И., Мудрак Н. С., Руденко Л. Г., Гамбарян А. С., Дрыгин В. В.

Аннотация

Сравнивали 4 экспериментальных штамма, сконструированных в лаборатории молекулярной биологии вирусов гриппа ФГБHУ «ИПВЭ им. М.П. Чумакова», с апатогенным H5N3-вирусом А/duck/Moscow/4182/2010 (dk/4182) в качестве живой ветеринарной вакцины. Экспериментальные штаммы содержали Н5-гемагглютинин от вакцинного штамма VNH 5N1-PR8/CDC-RG (VN-PR8) или аттенуированного вируса, полученного путем селекции из высоковирулентного А/сhicken/Kurgan/3/2005 (H5N1). Внутренние гены и нейраминидаза экспериментальных штаммов были либо от холодоадаптированного донора аттенуации A/Leningrad/134/17/57 (H2N2), либо от непатогенного H6N2-вируса A/gull/Moscow/3100/2006. В опытах на мышах было показано, что все испытанные штаммы непатогенны для мышей, после однократной вакцинации вызывают высокий прирост антител и хорошо защищают от последующего заражения высоковирулентным вирусом H5N1. Индекс патогенности на курах всех экспериментальных штаммов равен нулю при значении 2,89 для вируса А/chicken/Kurgan/3/2005 (H5N1). Сравнивали разные схемы вакцинации цыплят. Штамм dk/4182 при аэрозольной вакцинации 1-дневных цыплят был апатогенен, обеспечивал высокий и равномерный прирост антител и полную защиту от последующего заражения вирусом А/сhicken/Kurgan/3/2005.
Список литературы

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27. Ломакина Н.Ф., Боравлева Е.Ю., Кропоткина Е.А., Ямникова С.С., Дрыгин В.В., Гамбарян А.С. Аттенуация вируса гриппа А/ курица/Курган/3/2005 (H5N1) селекцией в условиях, имитирующих жизненный цикл вирусов диких уток. Молекулярная генетика, микpобиология и виpусология. 2011; 3: 35–41.

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Problems of Virology. 2015; 60: 44-49

Testing of apathogenic influenza virus H5N3 as a poultry live vaccine

Boravleva E. Y., Chvala I. A., Lomakina N. F., Repin P. I., Mudrak N. S., Rudenko L. G., Gambaryan A. S., Drygin V. V.

Abstract

Four H5N2 experimental vaccine strains and the apathogenic wild duck H5N3 influenza virus A/duck/ Moscow/4182/2010 (dk/4182) were tested as a live poultry vaccine. Experimental strains had the hemagglutinin of the A/Vietnam/1203/04 strain lacking the polybasic HA cleavage site or the hemagglutinin from attenuated virus (Ku/at) that was derived from the highly pathogenic influenza virus A/chicken/Kurgan/3/2005 (H5N1). The hemagglutinin of the Ku-at has the amino acid substitutions Asp54/Asn and Lys222/Thr in HA1 and Val48/Ile and Lys131/Thr in HA2, while maintaining the polybasic HA cleavage site at an invariable level. The other genes of these experimental strains were from the H2N2 cold-adapted master strain A/Leningrad/134/17/57 (VN-Len and Ku-Len) or from the apathogenic H6N2 virus A/gull/Moscow/3100/2006 (VN-Gull and Ku-Gull). A single immunization of mice with all tested strains elicited a high level of serum antibodies and provided complete protection against the challenge with the lethal dose of A/chicken/Kurgan/3/05. The pathogenicity indexes of the Ku-at and the other strains for chicken were virtually zero, whereas the index of the parent H5N1 virus A/chicken/Kurgan/3/2005 was 2.98. Intravenous, intranasal, and aerosol routes of vaccination were compared. It was shown that the strain dk/4182 was totally apathogenic for one-day-old chicken and provided complete protection against the highly pathogenic H5N1 virus.
References

1. Jung E.J., Lee K.H., Seong B.L. Reverse genetic platform for inactivated and live-attenuated influenza vaccine. Exp. Mol. Med. 2010; 42(2): 116–21.

2. Kim J., Kayali G., Walker D., Forrest H.L Webby R.J., Webster R.G. et al. Puzzling inefficiency of H5N1 influenza vaccines in Egyptian poultry. PNAS. 2010; 107(24): 11044–9.

3. Gendon Yu.Z. Preimushchestva i nedostatki inaktivirovannoi i zhivoi vaktsiny protiv grippa. Voprosy virusologii. 2004; 49(4): 4–12.

4. Chien K.Y., Blackburn K., Liu H.C., Goshe M.B. Proteomic and Phosphoproteomic Analysis of shicken Embryo Fibroblasts Infected with Cell Culture-Attenuated and Vaccine Strains of Marek’s Disease Virus. J. Proteome Res. 2012; 11(12): 5663–77.

5. Evans J.D., Leigh S.A., Purswell J.L., Jacob R., Peebles E.D., Collier S.D. et al. A comparative study of live attenuated F strain-derived Mycoplasma gallisepticum vaccines. Avian Dis. 2012; 56: 396–401.

6. Vagnozzi A., Zavala G., Riblet S.M., Mundt A., García M. Protection induced by commercially available live-attenuated and recombinant viral vector vaccines against infectious laryngotracheitis virus in broiler chickens. Avian Pathol. 2012; 41(1): 21–31.

7. Cornelissen L.A., de Leeuw O.S., Tacken M.G., Klos H.C., de Vries R.P., de Haan C.A. et al. Protective efficacy of Newcastle disease virus expressing soluble trimeric hemagglutinin against highly pathogenic H5N1 influenza in chickens and mice. PLoS One. 2012; 7(8): e44447.

8. Park M.S., Steel J., García-Sastre A., Swayne D., Palese P. Engineered viral vaccine constructs with dual specificity: avian influenza and Newcastle disease. Proc. Natl. Acad. Sci. U S A. 2006; 103(21): 8203–8.

9. Pavlova S.P., Veits J., Mettenleiter T.C., Fuchs W. Live vaccination with an H5-hemagglutinin-expressing infectious laryngotracheitis virus recombinant protects chickens against different highly pathogenic avian influenza viruses of the H5 subtype. Vaccine. 2009; 27(37): 5085–90.

10. Cui H., Gao H., Cui X., Zhao Y., Shi X., Wang Y. et al. Avirulent Marek’s Disease Virus Type 1 Strain 814 Vectored Vaccine Expressing Avian Influenza (AI) Virus H5 Haemagglutinin Induced Better Protection Than Turkey Herpesvirus Vectored AI Vaccine. PLoS One. 2013; 8(1): e53340.

11. Suguitan A.L. Jr, McAuliffe J., Mills K.L., Jin H., Duke G., Subbarao K. et al. Live, Attenuated Influenza A H5N1 Candidate Vaccines Provide Broad Cross-Protection in Mice and Ferrets. PLoS Med. 2006; 3(9): 1541–54.

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20. Krenn B.M., Egorov A., Romanovskaya-Romanko E., Wolschek M., Nakowitsch S., Ruthsatz T. et al. Single HA2 mutation increases the infectivity and immunogenicity of a live attenuated H5N1 intranasal influenza vaccine candidate lacking NS1. PLoS One. 2011; 6(4): e18577. doi: 10.1371

21. Steel J., Lowen A.C., Pena L., Angel M., Solórzano A., Albrecht R. et al. Live attenuated influenza viruses containing NS1 truncations as vaccine candidates against H5N1 highly pathogenic avian influenza. J. Virol. 2009; 83(4): 1742–53.

22. Zhou H., Zhu J., Tu J., Zou W., Hu Y., Yu Z. et al. Effect on virulence and pathogenicity of H5N1 influenza A virus through truncations of NS1 eIF4GI binding domain. J. Infect. Dis. 2010; 202(9): 1338–46.

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26. Ito T., Goto H., Yamamoto E., Tanaka H., Takeuchi M., Kuwayama M. et al. Generation of a highly pathogenic avian influenza A virus from an avirulent field isolate by passaging in chickens. J. Virol. 2001; 75: 4439–43.

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29. El-Zoghby E.F., Arafa A.S., Kilany W.H., Aly M.M., Abdelwhab E.M., Hafez H.M. Isolation of avian influenza H5N1 virus from vaccinated commercial layer flock in Egypt. Virol. J. 2012; 9(1): 294

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31. Murphy B.R., Sly D.L., Tierney E.L., Hosier N.T., Massicot J.G., London W.T. et al. Reassortant virus derived from avian and human influenza A viruses is attenuated and immunogenic in monkeys. Science. 1982; 218: 1330–2.