tetano
Editor, Senior Moderator
J Vet Sci. 2017 Aug 31;18(S1):299-306. doi: 10.4142/jvs.2017.18.S1.299.
[h=1]Optimized clade 2.3.2.1c H5N1 recombinant-vaccine strains against highly pathogenic avian influenza.[/h] Jang JW[SUP]1,[/SUP][SUP]2[/SUP], Lee CY[SUP]1,[/SUP][SUP]2[/SUP], Kim IH[SUP]3[/SUP], Choi JG[SUP]4[/SUP], Lee YJ[SUP]5[/SUP], Yuk SS[SUP]6[/SUP], Lee JH[SUP]6[/SUP], Song CS[SUP]6[/SUP], Kim JH[SUP]1,[/SUP][SUP]2[/SUP], Kwon HJ[SUP]7,[/SUP][SUP]2[/SUP].
[h=3]Author information[/h]
[h=3]Abstract[/h] 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.
[h=4]KEYWORDS:[/h] influenza A virus H5N1 subtype; polymerase basic 2 gene; reverse genetics; vaccines; virulence
PMID: 28859269 DOI: 10.4142/jvs.2017.18.S1.299
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[h=1]Optimized clade 2.3.2.1c H5N1 recombinant-vaccine strains against highly pathogenic avian influenza.[/h] Jang JW[SUP]1,[/SUP][SUP]2[/SUP], Lee CY[SUP]1,[/SUP][SUP]2[/SUP], Kim IH[SUP]3[/SUP], Choi JG[SUP]4[/SUP], Lee YJ[SUP]5[/SUP], Yuk SS[SUP]6[/SUP], Lee JH[SUP]6[/SUP], Song CS[SUP]6[/SUP], Kim JH[SUP]1,[/SUP][SUP]2[/SUP], Kwon HJ[SUP]7,[/SUP][SUP]2[/SUP].
[h=3]Author information[/h]
[h=3]Abstract[/h] 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.
[h=4]KEYWORDS:[/h] influenza A virus H5N1 subtype; polymerase basic 2 gene; reverse genetics; vaccines; virulence
PMID: 28859269 DOI: 10.4142/jvs.2017.18.S1.299
Free full text