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Title: ENGINEERED VIRAL VACCINE CONSTRUCTS WITH DUAL SPECIFICITY: AVIAN INFLUENZA AND NEWCASTLE DISEASE

Author
item PARK, MAN-SEONG - MT. SINAI - NEW YORK, NY
item STEEL, JOHN - MT. SINAI - NEW YORK, NY
item GARCIA-SASTRE, ADOLFO - MT. SINAI - NEW YORK, NY
item Swayne, David
item PALESE, PETER - MT. SINAI - NEW YORK, NY

Submitted to: Proceedings of the National Academy of Sciences (PNAS)
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 5/1/2006
Publication Date: 5/23/2006
Citation: Park, M., Steel, J., Garcia-Sastre, A., Swayne, D.E., Palese, P. 2006. Engineered viral vaccine constructs with dual specificity: Avian Influenza and Newcastle disease. Proceedings of the National Academy of Sciences. 103(21):8203-8206.

Interpretive Summary: High pathogenicity avian influenza (HPAI), including H5N1 strain, and virulent Newcastle disease (vvNDV)are the two diseases that cause severe high mortality disease of poultry and limit international trade in poultry and poultry products. This study developed two live chimeric (hybrid) viruses that each provide protection from both HPAI and vvNDV when given in the upper respiratory tract. These viruses have potential as vaccines with advantages of mass immunization technologies and protection from two deadly poultry diseases.

Technical Abstract: Avian influenza viruses of the H5 and H7 hemagglutinin subtypes and Newcastle disease virus are important pathogens in poultry worldwide. Specifically, the H5N1 highly pathogenic avian influenza virus is a particular threat as it has now occurred in more than 40 countries on several continents. Since most chickens worldwide are vaccinated with a live Newcastle disease virus vaccine, we embarked on developing vaccine prototypes which would have dual specificity and allow immunization against avian influenza as well as Newcastle disease through low cost respiratory application. Using reverse genetics, we constructed a chimeric avian influenza virus which expressed the ectodomain of the hemagglutinin/neuraminidase gene of Newcastle disease virus instead of the neuraminidase gene of the H5N1 avian influenza virus. A second approach to creating a bivalent vaccine was based on expressing the ectodomain of an H7 avian influenza virus hemagglutinin in a fusogenic (attenuated) Newcastle disease virus background. The insertion into the Newcastle disease virus genome of the foreign gene (containing only its ectodomain, with the transmembrane and cytoplasmic domains derived from the F protein of Newcastle disease virus) 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 velogenic Newcastle disease virus. 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.