Author
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PUSHKO, PETER - Medigen, Inc |
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TRETYAKOVA, IRINA - Medigen, Inc |
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HIDAJAT, RACHMAT - Medigen, Inc |
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Zsak, Aniko |
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CHRZASTEK, KLAUDIA - Orise Fellow |
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TUMPEY, TERRENCE - Chinese Center For Disease Control |
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Kapczynski, Darrell |
Submitted to: Virology
Publication Type: Peer Reviewed Journal Publication Acceptance Date: 12/1/2016 Publication Date: 12/6/2016 Publication URL: http://handle.nal.usda.gov/10113/5729155 Citation: Pushko, P., Tretyakova, I., Hidajat, R., Zsak, A., Chrzastek, K., Tumpey, T.M., Kapczynski, D.R. 2016. Virus-like particles comprising H5, H7 and H9 hemagglutinins elicit protective immunity to heterologous avian influenza viruses in chickens. Virology. 501:176-182. doi:10.1016/j.virol.2016.12.001. Interpretive Summary: Avian influenza (AI) viruses circulating in wild birds pose a serious threat to public health. Human and veterinary vaccines against multiple AI subtypes are needed. Here we prepared triple-subtype, H5/H7/H9 VLPs that co-localized H5, H7 and H9 antigens derived from the H5N1, H7N3 and H9N2 AI subtypes. VLPs also contained influenza neuraminidase and retroviral gag protein. The VLPs were prepared using baculovirus expression vector and their biochemical, functional and antigenic characteristics have been determined including hemagglutination and neuraminidase enzyme activities. VLPs were further evaluated in a chicken AI challenge model for safety, immunogenicity and protective efficacy against heterologous AI viruses including H5N2, H7N3 and H9N2 subtypes. All vaccinated birds survived challenges with H5N2 and H7N3 highly pathogenic AI (HPAI) viruses, while all controls died. For low pathogenic AI H9N2 challenge no mortality was observed following challenge, however, immune responses to the vaccine were detected. Thus, triple-subtype H5/H7/H9 VLPs induced protection against multiple AI challenges. Technical Abstract: Avian influenza (AI) viruses circulating in wild birds pose a serious threat to public health. Human and veterinary vaccines against AI subtypes are needed. Here we prepared triple-subtype VLPs that co-localized H5, H7 and H9 antigens derived from H5N1, H7N3 and H9N2 viruses. VLPs also contained influenza N1 neuraminidase and retroviral gag protein. The H5/H7/H9/N1/gag VLPs were prepared using baculovirus expression. Biochemical, functional and antigenic characteristics were determined including hemagglutination and neuraminidase enzyme activities. VLPs were further evaluated in a chicken AI challenge model for safety, immunogenicity and protective efficacy against heterologous AI viruses including H5N2, H7N3 and H9N2 subtypes. All vaccinated birds survived challenges with H5N2 and H7N3 highly pathogenic AI (HPAI) viruses, while all controls died. Immune response was also detectable after challenge with low pathogenicity AI (LPAI) H9N2 virus suggesting that H5/H7/H9/N1/gag VLPs represent a promising approach for the development of broadly protective AI vaccine. |