Engineered viral vaccine constructs with dual specificity: Avian influenza and Newcastle disease

Man-Seong Park, John Steel, Adolfo García-Sastre, David Swayne, Peter Palese

Research output: Contribution to journalArticle

162 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)8203-8208
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume103
Issue number21
DOIs
Publication statusPublished - 2006 May 23
Externally publishedYes

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Keywords

  • Avian influenza virus
  • Chicken
  • Hemagglutinin
  • Newcastle disease virus
  • Pandemic

ASJC Scopus subject areas

  • General
  • Genetics

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