Optimized clade 2.3.2.1c H5N1 recombinant-vaccine strains against highly pathogenic avian influenza

Jin Wook Jang, Chung Young Lee, Il hwan Kim, Jun Gu Choi, Youn Jeong Lee, Seong Su Yuk, Ji Ho Lee, Chang Seon Song, Jae Hong Kim, Hyuk Joon Kwon

Research output: Contribution to journalArticlepeer-review

8 Scopus citations

Abstract

A/Puerto Rico/8/34 (PR8)-derived recombinant viruses have been used for seasonal flu vaccines; however, they are insufficient for vaccines against some human-fatal H5N1 highly pathogenic avian influenza (HPAI) viruses (HPAIV) due to low productivity. Additionally, the polymerase basic 2 (PB2) protein, an important mammalian-pathogenicity determinant, of PR8 possesses several mammalian-pathogenic mutations. We previously reported two avian PB2 genes (01310 and 0028) related to efficient replication in embryonated chicken eggs (ECEs) and nonpathogenicity in BALB/c mice. In this study, we generated PR8-derived H5N1 recombinant viruses harboring hemagglutinin (attenuated) and neuraminidase genes of a clade 2.3.2.1c H5N1 HPAIV (K10-483), as well as the 01310 or 0028 PB2 genes, and investigated their replication and immunogenicity. Compared with a control virus harboring six internal PR8 genes (rK10-483), the recombinant viruses possessing the 01310 and 0028 PB2 genes showed significantly higher replication efficiency in ECEs and higher antibody titers in chickens. In contrast to rK10-483, none of the viruses replicated in BALB/c mice, and all showed low titers in Madin-Darby canine kidney cells. Additionally, the recombinant viruses did not induce a neutralization antibody but elicited decreased protective immune responses against K10-483 in mice. Thus, the highly replicative and mammalian nonpathogenic recombinant H5N1 strains might be promising vaccine candidates against HPAI in poultry.

Original languageEnglish
Pages (from-to)299-306
Number of pages8
JournalJournal of Veterinary Science
Volume18
DOIs
StatePublished - 2017

Keywords

  • Influenza A virus H5N1 subtype
  • Polymerase basic 2 gene
  • Reverse genetics
  • Vaccines
  • Virulence

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