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KMID : 0893420170180000299
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Journal of Veterinary Science
2017 Volume.18 No. 0 p.299 ~ p.306
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Optimized clade 2.3.2.1c H5N1 recombinant-vaccine strains against highly pathogenic avian influenza
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Jang Jin-Wook
Lee Chung-Young
Kim Il-Hwan
Choi Jun-Gu
Lee Youn-Jeong
Yuk Seong-Su
Lee Ji-Ho
Song Chang-Seon
Kim Jae-Hong
Kwon Hyuk-Joon
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Abstract
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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.
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KEYWORD
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influenza A virus H5N1 subtype, polymerase basic 2 gene, reverse genetics, vaccines, virulence
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