- Удаление гена, кодирующего NS1 белок вируса гриппа сероподтипа H5N1 в комбинации с модификацией сайта расщепления НА - эффективный метод аттенуации высокопатогенных штаммов вируса гриппа птиц.
- Интраназальная иммунизация ΔNS1 вакцинным кандидатом сероподтипа H5N1 вызывает кроссреактивный и протективный иммунитет при отсутствии вирусной репродукции.
- Высокий уровень рН активации НА (5,8 - 6,0) высокопатогенных штаммов вируса гриппа птиц сероподтипа H5N1 - главный фактор низкой инфекционности и иммуногенности этих вирусов для млекопитающих.
- Адаптация сезонных штаммов вируса гриппа человека к росту в тканевых культурах при стандартных условиях приводит к появлению дестабилизирующих мутаций в НА, вызывающих снижение иммуногености полученных на их основе вакцинных штаммов живых интраназальных вакцин.
- Культивирование вирусов в тканевой культуре при пониженной кислотности среды предотвращает появление адаптационных мутаций в НА вируса гриппа и позволяет улучшить урожайность и иммуногенность производимых по данной технологии вакцинных штаммов для живых и инактивированных вакцин.
1.US 2010/0172934 A1 Method for production of pH stable enveloped viruses. Krenn B., Wolschek M., Romanova J., Egorov A., Nakowitsch S. (Заявка подана)
2.US 7,494,659B2 Live attenuated influenza vaccine. Katinger H., Egorov A., Ferko B., Romanova J., Katinger D.
Научные обзоры
Romanova J. The fight against new types of influenza virus. Biotechnol J. 2006; 1(12):1381-92.
Статьи в реферируемых журналах
1.Romanova, J. R., T. A. Ermachenko, G. I. Alexandrova, and G. A. Tannock. Interference between cold-adapted (ca) influenza A and B vaccine reassortants or between ca reassortants and wild-type strains in eggs and mice. Vaccine., 1994; 12:23-27.
2.Tannock, G. A., J. R. Romanova, and J. A. Paul. The immunogenicity of reassortants of the cold-adapted influenza A master strain A/Ann Arbor/6/60 is determined by both the genes for cold- adaptation and the haemagglutinin gene. Arch Virol., 1995; 140:201-209.
3.Romanova, J. R., G. A. Tannock, and G. I. Alexandrova. Protective responses in mice to vaccination with multiply administered cold-adapted influenza vaccine reassortants and wild-type viruses. Vaccine., 1997; 15:653-658.
4.Ferko, B., D. Katinger, A. Grassauer, A. Egorov, J. Romanova, B. Niebler, H. Katinger, and T. Muster. Chimeric influenza virus replicating predominantly in the murine upper respiratory tract induces local immune responses against human immunodeficiency virus type 1 in the genital tract. J Infect Dis., 1998; 178:1359-1368.
5.Egorov, A., S. Brandt, S. Sereinig, J. Romanova, B. Ferko, D. Katinger, A. Grassauer, G. Alexandrova, H. Katinger, and T. Muster. Transfectant influenza A viruses with long deletions in the NS1 protein grow efficiently in Vero cells. J Virol., 1998; 72: 6437-6441.
6.Grassauer, A., A. Y. Egorov, B. Ferko, I. Romanova, H. Katinger, and T. Muster. A host restriction-based selection system for influenza haemagglutinin transfectant viruses. J. Gen Virol., 1998; 79:1405-1409.
7.Ferko B, Stasakova J, Sereinig S, Romanova J, Katinger D, Niebler B, Katinger H, Egorov A. Hyperattenuated recombinant influenza A virus nonstructural – protein -encoding vectors induce human immunodeficiency virus type 1 Nef-specific systemic and mucosal immune responses in mice. J Virol., 2001; 75(19): 8899-908.
8.Romanova J, Katinger D, Ferko B, Voglauer R, Mochalova L, Bovin N, Lim W, Katinger H, Egorov A. Distinct host range of influenza H3N2 virus isolates in Vero and MDCK cells is determined by cell specific glycosylation pattern. Virology., 2003; 307(1): 90-7.
9.Mochalova L, Gambaryan A, Romanova J, Tuzikov A, Chinarev A, Katinger D, Katinger H, Egorov A, Bovin N. Receptor-binding properties of modern human influenza viruses primarily isolated in Vero and MDCK cells and chicken embryonated eggs. Virology., 2003; 313(2): 473-80.
10.Katinger D, Romanova J, Ferko B, Fekete H, Egorov A. Effect of a single mutation in neuraminidase on the properties of Influenza B virus isolates. Arch Virol., 2004; 149(1): 173-81.
11.Kittel C, Sereinig S, Ferko B, Stasakova J, Romanova J, Wolkerstorfer A, Katinger H, Egorov A. Rescue of influenza virus expressing GFP from the NS1 reading frame. Virology., 2004; 324(1): 67-73.
12.Romanova J, Katinger D, Ferko B, Vcelar B, Sereinig S, Kuznetsov O, Stukova M, Erofeeva M, Kiselev O, Katinger H, Egorov A. Live cold-adapted influenza A vaccine produced in Vero cell line. Virus Res., 2004; 103(1-2): 187-93.
13.Katinger D, Mochalova L, Chinarev A, Bovin N, Romanova J. Specificity of neuraminidase activity from influenza viruses isolated in different hosts tested with novel substrates. Arch Virol., 2004; 149(11): 2131-40.
14.Stasakova J, Ferko B, Kittel C, Sereinig S, Romanova J, Katinger H, Egorov A. Influenza A mutant viruses with altered NS1 protein function provoke caspase-1 activation in primary human macrophages, resulting in fast apoptosis and release of high levels of interleukins 1beta and 18. J Gen Virol., 2005; 86(Pt 1): 185-95.
15.Kittel C, Ferko B, Kurz M, Voglauer R, Sereinig S, Romanova J, Stiegler G, Katinger H, Egorov A. Generation of an influenza A virus vector expressing biologically active human interleukin-2 from the NS gene segment. J Virol., 2005; 79(16): 10672-7.
16.E.M.Rapoport, L.V.Mochalova, H.-J.Gabius, J.Romanova, N.V.Bovin. Search for additional influenza virus to cell interactions. Glycoconj.J., 2006; 23: 115-125.
17.Ferko B, Kittel C, Romanova J, Sereinig S, Katinger H, Egorov A. Live attenuated influenza virus expressing human interleukin-2 reveals increased immunogenic potential in young and aged hosts. J Virol., 2006; 80(23): 11621-7.
18.Wressnigg N, Voss D, Wolff T, Romanova J, Ruthsatz T, Mayerhofer I, Reiter M, Nakowitsch S, Humer J, Morokutti A, Muster T, Egorov A, Kittel C. Development of a live-attenuated influenza B DeltaNS1 intranasal vaccine candidate. Vaccine., 2009; 27(21): 2851-7.
19.Romanova J, Krenn BM, Wolschek M, Ferko B, Romanovskaja-Romanko E, Morokutti A, Shurygina AP, Nakowitsch S, Ruthsatz T, Kiefmann B, Kцnig U, Bergmann M, Sachet M, Balasingam S, Mann A, Oxford J, Slais M, Kiselev O, Muster T, Egorov A. Preclinical evaluation of a replication-deficient intranasal DeltaNS1 H5N1 influenza vaccine. PLoS One., 2009; 4(6): e5984.
20.Wacheck V, Egorov A, Groiss F, Pfeiffer A, Fuereder T, Hoeflmayer D, Kundi M, Popow-Kraupp T, Redlberger-Fritz M, Mueller CA, Cinatl J, Michaelis M, Geiler J, Bergmann M, Romanova J, Roethl E, Morokutti A, Wolschek M, Ferko B, Seipelt J, Dick-Gudenus R, Muster T. A novel type of influenza vaccine: safety and immunogenicity of replication-deficient influenza virus created by deletion of the interferon antagonist NS1 J Infect Dis., 2010; 201(3): 354-62.
21.Krenn BM, Egorov A, Romanovskaya-Romanko E, Wolschek M, Nakowitsch S, Ruthsatz T, Kiefmann B, Morokutti A, Humer J, Geiler J, Cinatl J, Michaelis M, Wressnigg N, Sturlan S, Ferko B, Batishchev OV, Indenbom AV, Zhu R, Kastner M, Hinterdorfer P, Kiselev O, Muster T, Romanova J. 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.
22.Nakowitsch S, Wolschek M, Morokutti A, Ruthsatz T, Krenn BM, Ferko B, Ferstl N, Triendl A, Muster T, Egorov A, Romanova J. Mutations affecting the stability of the haemagglutinin molecule impair the immunogenicity of live attenuated H3N2 intranasal influenza vaccine candidates lacking NS1. Vaccine., 2011; 29(19): 3517-24.
23. Roethl E, Gassner M, Krenn B.M., Romanovskaya-Romanko E.A., Seper H, Romanova J, Nakowitsch S, Sturlan S, Wolschek M, Sirotkin A, Kiselev O, Muster T, Egorov A. Antimycotic-antibiotic amphotericin B promotes influenza virus replication in cell culture. J Virol., 2011; 85(21): 11139-45.