title: Engineered viral vaccine constructs with dual specificity: avian influenza and Newcastle disease.
abstract: Avian influenza viruses of the H5 and H7 hemagglutinin subtypes, and Newcastle disease virus (NDV), are important pathogens in poultry worldwide. Specifically, the highly pathogenic H5N1 avian influenza virus is a particular threat because it has now occurred in more than 40 countries on several continents. Inasmuch as most chickens worldwide are vaccinated with a live NDV vaccine, we embarked on the development of vaccine prototypes that would have dual specificity and would allow a single immunization against both avian influenza and Newcastle disease. Using reverse genetics, we constructed a chimeric avian influenza virus that expressed the ectodomain of the hemagglutinin-neuraminidase gene of NDV instead of the neuraminidase protein of the H5N1 avian influenza virus. Our second approach to creating a bivalent vaccine was based on expressing the ectodomain of an H7 avian influenza virus hemagglutinin in a fusogenic and attenuated NDV background. The insertion into the NDV genome of the foreign gene (containing only its ectodomain, with the transmembrane and cytoplasmic domains derived from the F protein of NDV) resulted in a chimeric virus with enhanced incorporation of the foreign protein into virus particles. A single immunization of chickens with this improved vaccine prototype virus induced not only a 90% protection against an H7N7 highly pathogenic avian influenza virus, but also complete immunity against a highly virulent NDV. We propose that chimeric constructs should be developed for convenient, affordable, and effective vaccination against avian influenza and Newcastle disease in chickens and other poultry.
authors.affiliation: Department of Microbiology, Mount Sinai School of Medicine, New York, NY 10029, USA.
authors.forename: Man-Seong
authors.initials: MS
authors.lastname: Park
authors.forename: John
authors.initials: J
authors.lastname: Steel
authors.forename: Adolfo
authors.initials: A
authors.lastname: García-Sastre
authors.forename: David
authors.initials: D
authors.lastname: Swayne
authors.forename: Peter
authors.initials: P
authors.lastname: Palese
mesh_terms: D000818:Animals; D000914:Antibodies, Viral / Q000737:chemistry; D000918:Antibody Specificity; D002460:Cell Line; D002645:Chickens; D002522:Chlorocebus aethiops; D006801:Humans; D053124:Influenza A Virus, H5N1 Subtype; D053126:Influenza A Virus, H7N7 Subtype; D005585:Influenza in Birds / Q000517:prevention & control / Q000821:virology*; D009521:Newcastle Disease / Q000517:prevention & control / Q000821:virology*; D017434:Protein Structure, Tertiary; D014709:Vero Cells; D014765:Viral Vaccines / Q000737:chemistry*
chemical_list: D000914:Antibodies, Viral; D014765:Viral Vaccines