Статья

Safety, immunogenicity, and protective efficacy of a chimeric a/b live attenuated influenza vaccine in a mouse model

E. Stepanova, E. Krutikova, P. Wong, V. Matyushenko, E. Bazhenova, I. Isakova-Sivak, L. Rudenko,
2021

Influenza A and B viruses cause significant morbidity and mortality worldwide. Current influenza vaccines are composed of three or four strains: A/H1N1, A/H3N2, and B (Victoria and Yamagata lineages). It is of great interest if immunization against both type A and B influenza viruses can be combined in a single vaccine strain, thus reducing the cost of vaccine production and the possibility of strain interference within the multicomponent vaccine. In the current study, we developed an experimental live cold-adapted influenza intertype reassortant (influenza A and B) vaccine on the live attenuated influenza vaccine (LAIV) A/Leningrad/134/17/57 backbone. Hemagglutinin (HA) and neuraminidase (NA) functional domains were inherited from the influenza B/Brisbane/60/2008 strain, whereas their packaging signals were substituted with appropriate frag-ments of influenza A virus genes. The recombinant A/B virus efficiently replicated in eggs and Ma-din–Darby Canine Kidney (MDCK) cells under optimal conditions, temperature-sensitive phenotype was maintained, and its antigenic properties matched the influenza B parental virus. The chimeric vaccine was attenuated in mice: after intranasal immunization, viral replication was seen only in nasal turbinates but not in the lungs. Immunological studies demonstrated the induction of IgG antibody responses against the influenza A and B virus, whereas hemagglutination inhibition (HAI) and neutralizing antibodies were detected only against the influenza B virus, resulting in significant protection of immunized animals against influenza B virus challenge. IFNγ-secreting CD8 effector memory T cells (CD44+CD62L−) were detected in mouse splenocytes after stimulation with the specific influenza A peptide (NP366); however, the T-cell response was not sufficient to protect animals against infection with a high-dose mouse-adapted A/California/07/2009 (H1N1pdm09) virus, most probably due to the mismatch of key T-cell epitopes of the H1N1 virus and the LAIV backbone. Overall, generation of the chimeric A/B LAIV virus on a licensed LAIV backbone demonstrated prospects for the development of safe and efficacious vaccine candidates that afford combined protection against both type A and type B influenza viruses; however, further optimization of the T-cell epitope content within the LAIV backbone may be required. © 2021 by the authors. Licensee MDPI, Basel, Switzerland.

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

Метаданные

Об авторах
  • E. Stepanova
    Institute of Experimental Medicine, Saint Petersburg, 197376, Russian Federation
  • E. Krutikova
  • P. Wong
  • V. Matyushenko
  • E. Bazhenova
  • I. Isakova-Sivak
  • L. Rudenko
Название журнала
  • Microorganisms
Том
  • 9
Выпуск
  • 2
Страницы
  • 1-24
Издатель
  • MDPI AG
Тип документа
  • journal article
Тип лицензии Creative Commons
  • CC
Правовой статус документа
  • Свободная лицензия
Источник
  • scopus