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J Virol. 2017 Jan 11. pii: JVI.01693-16. doi: 10.1128/JVI.01693-16. [Epub ahead of print]
Vaccine efficacy of an inactivated, chimeric HA H9/H5N2 avian influenza virus and its suitability for the marker vaccine strategy.
Kim SM1,2, Kim YI1,2, Park SJ1,2, Kim EH1,2, Kwon HI1,2, Si YJ1,2, Lee IW1, Song MS1,2, Choi YK3,2.
Author information
Abstract
In order to produce a dual effective vaccine against H9 and H5 avian influenza viruses that aligns with the DIVA (differentiating infected from vaccinated animals) strategy, we generated a chimeric H9/H5N2 recombinant vaccine which expressed the whole HA1 region of A/CK/Korea/04163/04 H9N2 and HA2 region of recent HPAI A/MD/Korea/W452/14 H5N8 viruses. The Chimeric H9/H5N2 virus showed similar in vitro and in vivo growth properties and virulence to the LPAI H9 influenza virus. An inactivated vaccine based on this chimeric virus induced serum neutralizing (SN) antibodies against both H9 and H5 viruses, but only induced cross-reactive hemmaglutination inhibition (HI) antibody against H9 viruses. Thus, this suggests its compatibility for use in the DIVA strategy against H5 strains. Further, the chimeric H9/H5N2 recombinant vaccine protected immunized chickens against lethal challenge by HPAI H5N8 viruses, and significantly attenuated virus shedding after both H9N2 and HPAI H5N8 infection. In mice, serological analyses confirmed that HA1 and HA2 stalk-specific antibody responses were induced by vaccination and that the DIVA principle could be employed through use of an HI assay against H5 viruses. Further, each HA1 and HA2 stalk-specific antibody response was sufficient to inhibit viral replication and protect the chimeric virus-immunized mice from lethal challenge with both mouse-adapted H9N2 and wild-type HPAI H5N1 viruses, although differences in the vaccine efficacy against homologous H9 virus (HA1-head domain immune mediated protection) and heterosubtypic H5 virus (HA2 stalk domain immune mediated protection) were observed.Taken together, these results demonstrate that the novel chimeric H9/H5N2 recombinant virus is a low pathogenic virus and this chimeric vaccine is suitable for a DIVA vaccine with broad-spectrum neutralizing antibody against H5 avian influenza viruses.
IMPORTANCE:
Current influenza virus killed vaccines predominantly induce anti-hemagglutinin (HA) antibodies which commonly strain-specific in that the antibodies have potent neutralizing activity against homologous strains, but do not cross-react with the HA of other influenza subtypes. In contrast, the HA2 stalk domain is relatively well conserved among subtypes and recently broadly-neutralizing antibodies against this domain have been isolated. Therefore, in light of the need for a vaccine strain that applies the DIVA strategy utilizing an HI assay and induces broad cross-protectivity against H5N1 and H9N2 viruses, we generated a novel chimeric H9/H5N1 virus that expresses the entire HA1 portion from H9N2 and the HA2 region of heterosubtypic H5N8. The chimeric H9/H5N2 recombinant vaccine protected immunized hosts against from the lethal challenge of H9N2 and HPAI H5N1 viruses with significantly attenuated virus shedding in immunized hosts. Therefore, this chimeric vaccine strategy is suitable as a DIVA vaccine against H5 avian influenza viruses.
Copyright ? 2017 American Society for Microbiology.
PMID: 28077631 DOI: 10.1128/JVI.01693-16
[PubMed - as supplied by publisher]
Vaccine efficacy of an inactivated, chimeric HA H9/H5N2 avian influenza virus and its suitability for the marker vaccine strategy.
Kim SM1,2, Kim YI1,2, Park SJ1,2, Kim EH1,2, Kwon HI1,2, Si YJ1,2, Lee IW1, Song MS1,2, Choi YK3,2.
Author information
Abstract
In order to produce a dual effective vaccine against H9 and H5 avian influenza viruses that aligns with the DIVA (differentiating infected from vaccinated animals) strategy, we generated a chimeric H9/H5N2 recombinant vaccine which expressed the whole HA1 region of A/CK/Korea/04163/04 H9N2 and HA2 region of recent HPAI A/MD/Korea/W452/14 H5N8 viruses. The Chimeric H9/H5N2 virus showed similar in vitro and in vivo growth properties and virulence to the LPAI H9 influenza virus. An inactivated vaccine based on this chimeric virus induced serum neutralizing (SN) antibodies against both H9 and H5 viruses, but only induced cross-reactive hemmaglutination inhibition (HI) antibody against H9 viruses. Thus, this suggests its compatibility for use in the DIVA strategy against H5 strains. Further, the chimeric H9/H5N2 recombinant vaccine protected immunized chickens against lethal challenge by HPAI H5N8 viruses, and significantly attenuated virus shedding after both H9N2 and HPAI H5N8 infection. In mice, serological analyses confirmed that HA1 and HA2 stalk-specific antibody responses were induced by vaccination and that the DIVA principle could be employed through use of an HI assay against H5 viruses. Further, each HA1 and HA2 stalk-specific antibody response was sufficient to inhibit viral replication and protect the chimeric virus-immunized mice from lethal challenge with both mouse-adapted H9N2 and wild-type HPAI H5N1 viruses, although differences in the vaccine efficacy against homologous H9 virus (HA1-head domain immune mediated protection) and heterosubtypic H5 virus (HA2 stalk domain immune mediated protection) were observed.Taken together, these results demonstrate that the novel chimeric H9/H5N2 recombinant virus is a low pathogenic virus and this chimeric vaccine is suitable for a DIVA vaccine with broad-spectrum neutralizing antibody against H5 avian influenza viruses.
IMPORTANCE:
Current influenza virus killed vaccines predominantly induce anti-hemagglutinin (HA) antibodies which commonly strain-specific in that the antibodies have potent neutralizing activity against homologous strains, but do not cross-react with the HA of other influenza subtypes. In contrast, the HA2 stalk domain is relatively well conserved among subtypes and recently broadly-neutralizing antibodies against this domain have been isolated. Therefore, in light of the need for a vaccine strain that applies the DIVA strategy utilizing an HI assay and induces broad cross-protectivity against H5N1 and H9N2 viruses, we generated a novel chimeric H9/H5N1 virus that expresses the entire HA1 portion from H9N2 and the HA2 region of heterosubtypic H5N8. The chimeric H9/H5N2 recombinant vaccine protected immunized hosts against from the lethal challenge of H9N2 and HPAI H5N1 viruses with significantly attenuated virus shedding in immunized hosts. Therefore, this chimeric vaccine strategy is suitable as a DIVA vaccine against H5 avian influenza viruses.
Copyright ? 2017 American Society for Microbiology.
PMID: 28077631 DOI: 10.1128/JVI.01693-16
[PubMed - as supplied by publisher]