Статья

Live attenuated influenza vaccines against highly pathogenic H5N1avian influenza: Development and preclinical characterization

N. Larionova, I. Kiseleva, I. Isakova-Sivak, A. Rekstin, I. Dubrovina, E. Bazhenova, T. Ross, D. Swayne, L. Gubareva, V. Tsvetnitsky, E. Fedorova, E. Doroshenko, L. Rudenko,
2021

In this paper we describe the development and the outcomes of the preclinical studies of temperature-sensitive and cold-adapted candidates for live attenuated influenza vaccine (LAIV) based on highly pathogenic avian influenza viruses A/H5N1 with pandemic potential. The LAIV candidates were developed by methods of classical reassortment between H2N2 Master Donor Virus for Russian LAIV and H5N1 viruses generated by reverse genetics for inactivated vaccine. These reverse genetically generated viruses were chosen as a source of H5 hemagglutinin and contained a modified protease cleavage site believed to be associated with high virulence. The progeny of reassortment had 7:1 gene composition and were characterized by antigen specificity of the HA of the pandemic virus, a high growth rate in chicken embryos and their parameters of temperature sensitivity and cold adaptation confirmed preserved attenuation of the Master Donor Virus. In addition, one H5N1 LAIV 6:2 reassortant was generated by reverse genetics. When tested in appropriate animal models, all candidates for H5N2 LAIV vaccine were found to be safe, immunogenic and effective in protecting from severe disease, mortality and pathology caused by the homologues lethal challenge virus and they almost completely eliminated challenge virus replication in vaccinated animals. They did not appear to differ in tested properties from the reverse genetically generated H5N1 LAIV 6:2 reassortant which contained wild-type N1-neuraminidase in addition to H5-hemagglutinin. The most promising for further clinical trials has been considered a LAIV candidate to virus A/turkey/Turkey/1/2005 (H5N1, clade 2.2). © 2013 Larionova N, et al.

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  • 1. Version of Record от 2021-04-27

Метаданные

Об авторах
  • N. Larionova
    Institute of Experimental Medicine, St, Petersburg, Russian Federation
  • I. Kiseleva
    University of Pittsburgh, Pittsburgh, PA, United States
  • I. Isakova-Sivak
    Southeast Poultry Research Laboratory, Athens, GA, United States
  • A. Rekstin
    Centers for Disease Control and Prevention, Atlanta, GA, United States
  • I. Dubrovina
    PATH, United States
  • E. Bazhenova
  • T. Ross
  • D. Swayne
  • L. Gubareva
  • V. Tsvetnitsky
  • E. Fedorova
  • E. Doroshenko
  • L. Rudenko
Название журнала
  • Journal of Vaccines and Vaccination
Том
  • 4
Выпуск
  • 8
Страницы
  • -
Тип документа
  • journal article
Тип лицензии Creative Commons
  • CC
Правовой статус документа
  • Свободная лицензия
Источник
  • scopus