Abstract
Using plasmid-based reverse genetics, we generated a molecularly altered virus, H5N1/PR8-5B19, containing modified HA and NA genes from A/Goose/Guangdong/1/96 (GS/GD/1/96). In the H5N1/PR8-5B19 virus, the HA cleavage site was modified to resemble that of low-pathogenic avian strains and a portion of the NA stalk region was replaced by the immunodominant 5B19 epitope of the S2 glycoprotein of murine hepatitis virus (MHV). H5N1/PR8-5B19 is not lethal to embryonated eggs or chickens. Chickens immunized with the H5N1/PR8-5B19 inactivated vaccine produced high levels of HI antibody and a measurable antibody response against the MHV 5B19 epitope, and were fully protected against subsequent challenge with different highly pathogenic H5N1 avian influenza viruses. H5N1/PR8-5B19 is therefore an attractive marker vaccine candidate, eliciting a strong, protective antibody response and enabling serological discrimination between vaccinated and wild-type virus-infected chickens.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Antibodies, Viral / biosynthesis
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Antibodies, Viral / blood
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Antibody Formation
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Chickens / immunology*
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Chickens / virology*
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Glycoproteins / genetics
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Glycoproteins / immunology
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Hemagglutinin Glycoproteins, Influenza Virus / genetics
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Hemagglutinin Glycoproteins, Influenza Virus / immunology*
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Immunodominant Epitopes / genetics
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Influenza A Virus, H5N1 Subtype / genetics
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Influenza A Virus, H5N1 Subtype / immunology*
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Influenza A Virus, H5N1 Subtype / physiology
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Influenza Vaccines / genetics
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Influenza Vaccines / immunology*
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Influenza Vaccines / therapeutic use
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Influenza in Birds / prevention & control*
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Murine hepatitis virus / genetics
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Murine hepatitis virus / immunology
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Neuraminidase / genetics
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Neuraminidase / immunology
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Vaccination
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Vaccines, DNA
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Vaccines, Inactivated / genetics
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Vaccines, Inactivated / immunology
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Vaccines, Inactivated / therapeutic use
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Viral Proteins / genetics
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Viral Proteins / immunology
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Virus Replication
Substances
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Antibodies, Viral
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Glycoproteins
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Hemagglutinin Glycoproteins, Influenza Virus
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Immunodominant Epitopes
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Influenza Vaccines
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Vaccines, DNA
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Vaccines, Inactivated
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Viral Proteins
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NA protein, influenza A virus
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Neuraminidase