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

doi:10.1073/pnas.0602566103

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

*Department of Microbiology, Mount Sinai School of Medicine, New York, NY 10029; and
^†Southeast Poultry Research Laboratory, Agricultural Research Service, U.S. Department of Agriculture, Athens, GA 30605-2195

Contributed by Peter Palese, March 29, 2006

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.

Footnotes

^‡To whom correspondence should be addressed. E-mail: peter.palese{at}mssm.edu
Author contributions: M.-S.P., J.S., A.G.-S., and P.P. designed research; M.-S.P., J.S., and D.S. performed research; A.G.-S. and D.S. contributed new reagents/analytic tools; M.-S.P., J.S., A.G.-S., D.S., and P.P. analyzed data; and M.-S.P., J.S., D.S., and P.P. wrote the paper.
Conflict of interest statement: Mount Sinai School of Medicine owns patent positions for reverse genetics of negative-strand RNA viruses (A.G.-S. and P.P.).
Abbreviations:

Abbreviations:

HPAI,

high-pathogenicity avian influenza;

AIV,

avian influenza virus;

NDV,

Newcastle disease virus;

NA,

neuraminidase;

HN,

hemagglutinin–neuraminidase;

rNDV,

recombinant NDV;

HA,

hemagglutinin;

WSN,

influenza A/WSN/33 (H1N1) virus;

cHN,

chimeric HN;

EID50,

egg 50% infectious dose;

MDCK,

Madin–Darby canine kidney;

vRNA,

viral RNA;

CEF,

chicken embryo fibroblast;

MDT,

mean death time;

F,

fusion protein;

HI,

hemagglutination inhibition;

pNDV,

parental NDV;

vNDV,

velogenic NDV.
Freely available online through the PNAS open access option.