Статья

H7N9 live attenuated influenza vaccine is highly immunogenic, prevents virus replication, and protects against severe bronchopneumonia in ferrets

J. De, I. Isakova-Sivak, D. Van, S. Spijkers, J. Mouthaan, J. De, T. Smolonogina, P. Roholl, L. Rudenko,
2021

Avian influenza viruses continue to cross the species barrier, and if such viruses become transmissible among humans, it would pose a great threat to public health. Since its emergence in China in 2013, H7N9 has caused considerable morbidity and mortality. In the absence of a universal influenza vaccine, preparedness includes development of subtype-specific vaccines. In this study, we developed and evaluated in ferrets an intranasal live attenuated influenza vaccine (LAIV) against H7N9 based on the A/Leningrad/134/17/57 (H2N2) cold-adapted master donor virus. We demonstrate that the LAIV is attenuated and safe in ferrets and induces high hemagglutination- and neuraminidase-inhibiting and virus-neutralizing titers. The antibodies against hemagglutinin were also cross-reactive with divergent H7 strains. To assess efficacy, we used an intratracheal challenge ferret model in which an acute severe viral pneumonia is induced that closely resembles viral pneumonia observed in severe human cases. A single- and two-dose strategy provided complete protection against severe pneumonia and prevented virus replication. The protective effect of the two-dose strategy appeared better than the single dose only on the microscopic level in the lungs. We observed, however, an increased lymphocytic infiltration after challenge in single-vaccinated animals and hypothesize that this a side effect of the model. © 2016 The American Society of Gene & Cell Therapy.

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

Метаданные

Об авторах
  • J. De
    Centre for Infectious Disease Control, National Institute of Public Health and the Environment (RIVM), Bilthoven, 3720 BA, Netherlands
  • I. Isakova-Sivak
    Department of Virology, Institute of Experimental Medicine, Saint Petersburg, Russian Federation
  • D. Van
    Department of Virology, Central Veterinary Institute of Wageningen UR, Lelystad, Netherlands
  • S. Spijkers
    Microscope Consultancy, Weesp, Netherlands
  • J. Mouthaan
    BioNovion, Oss, Netherlands
  • J. De
    Genmab, Utrecht, Netherlands
  • T. Smolonogina
  • P. Roholl
  • L. Rudenko
Название журнала
  • Molecular Therapy
Том
  • 24
Выпуск
  • 5
Страницы
  • 991-1002
Ключевые слова
  • influenza vaccine; influenza vaccine; live vaccine; neutralizing antibody; virus antibody; animal experiment; animal model; Article; bronchopneumonia; cold acclimatization; cross reaction; disease severity; drug efficacy; drug safety; female; ferret; gene; growth inhibition; HA gene; immune response; in vitro study; Influenza A virus (H7N9); lymphocytic infiltration; NA gene; nonhuman; temperature sensitivity; vaccination; virogenesis; virus replication; virus strain; virus titration; animal; bronchopneumonia; disease model; drug effects; human; immunology; Influenza A virus (H7N9); intranasal drug administration; Mustela putorius furo; Orthomyxoviridae Infections; physiology; Administration, Intranasal; Animals; Antibodies, Neutralizing; Antibodies, Viral; Bronchopneumonia; Disease Models, Animal; Female; Ferrets; Humans; Influenza A Virus, H7N9 Subtype; Influenza Vaccines; Orthomyxoviridae Infections; Vaccines, Attenuated; Virus Replication
Издатель
  • Nature Publishing Group
Тип документа
  • journal article
Тип лицензии Creative Commons
  • CC
Правовой статус документа
  • Свободная лицензия
Источник
  • scopus