Submitted to: Cold Spring Harbor Meeting
Publication Type: Abstract Only
Publication Acceptance Date: 11/1/2001
Publication Date: 11/1/2001
Technical Abstract: Aquatic birds can be infected by influenza A viruses of 15 hemagglutinin (HA) and 9 neuraminidase (NA) subtypes and serve as a reservoir from which novel influenza subtypes can be introduced into humans and cause a pandemic. Candidate vaccines with H5N1 or H9N2 genes respectively, in a background of PR8 genes, were generated using reverse genetics. The H5 HA gene was modified by replacing the multibasic cleavage site associated wit high pathogenicity in chickens with the sequence seen in nonpathogenic avian viruses. The H9N2/PR8 candidate vaccine was generated by classical reassortment without modifying the genes. The antigenicity of the H5 and H9 HAs were preserved in the respective vaccine viruses. Both vaccine viruses replicated poorly in chickens following intravenous or intranasal inoculation. Unlike the H5N1 parent virus, neither H5N1/PR8 nor H9N2/PR8 were highly pathogenic for chickens. Both H5N1/PR8 and H9N2/PR8 replicated in lungs but failed to replicate in extrapulmonary tissues of mice following intranasal inoculation. Unlike the H5N1 and PR8 parent viruses, neither H5N1/PR8 nor H9N2/PR8 were lethal for BALB/c mice. In summary, the H5N1/PR8 and H9N2/PR8 viruses bear the genotypes and antigenicity desirable in candidate vaccines, accompanied by attenuation in chicken and mouse models.