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.