Assessment of retrovirus-expressed nucleoprotein as a vaccine against lethal influenza virus infections of chickens.
Hemagglutinin-based influenza vaccines stimulate protection in chickens that is limited to the serotype of the expressed hemagglutinin. To evaluate whether a more highly conserved influenza virus protein might stimulate a broader protective response, the influenza virus nucleoprotein (NP) was introduced into a retroviral vector (mRCAS/NP). NP is an internal influenza virus protein that has been shown to stimulate cytotoxic T-cell responses in influenza-virus-infected mice. Cells infected with mRCAS/NP expressed approximately 10% of the level of NP observed in influenza-virus-infected chicken embryo fibroblasts. Immunocompetent chicks were vaccinated intramuscularly with approximately 1 x 10(5) NP-expressing units of mRCAS/NP. Four weeks later, chicks were bled and challenged with a highly pathogenic avian influenza virus (A/Chicken/Victoria/1/85). The NP-expressing vector stimulated an influenza-virus-specific response, as indicated by the presence of antibody to NP, but failed to protect against the lethal challenge.
Brown
D W
DW
Department of Pathology, University of Massachusetts Medical Center, Worcester 01655.
Kawaoka
Y
Y
Webster
R G
RG
Robinson
H L
HL
D000818:Animals; D000914:Antibodies, Viral / Q000097:blood; D001354:Avian Leukosis Virus / Q000378:metabolism; D002645:Chickens / Q000276:immunology*; D005822:Genetic Vectors / Q000276:immunology; D009980:Influenza A virus / Q000276:immunology*; D007252:Influenza Vaccines / Q000096:biosynthesis / Q000276:immunology*; D005585:Influenza in Birds / Q000276:immunology; D019590:Nucleocapsid Proteins; D009698:Nucleoproteins / Q000096:biosynthesis / Q000276:immunology*; D011201:Poultry Diseases / Q000276:immunology* / Q000382:microbiology; D016601:RNA-Binding Proteins; D014614:Vaccines, Synthetic / Q000096:biosynthesis / Q000276:immunology; D014758:Viral Core Proteins / Q000096:biosynthesis / Q000276:immunology*
D000914:Antibodies, Viral; D007252:Influenza Vaccines; C048842:NP protein, Influenza A virus; D019590:Nucleocapsid Proteins; D009698:Nucleoproteins; D016601:RNA-Binding Proteins; D014614:Vaccines, Synthetic; D014758:Viral Core Proteins