Submitted to: Avian Diseases
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 3/5/2002
Publication Date: 8/1/2003
Citation: Matsuoka, Y., Chen, H., Cox, N., Subbarao, K., Beck, J.R., Swayne, D.E. 2003. Safety Evaluation In Chickens Of Candidate Human Vaccines Against Potential Pandemic Strains Of Influenza. Avian Diseases 47:926-930, 2003. Interpretive Summary: Vaccines are used to prevent influenza in people. However, the current vaccine strains do not protect against most strains of avian influenza, especially the H5N1 and H9N2 that have caused some human infections in Asia. These studies were undertaken to develop two new vaccine strains against avian influenza viruses for human use. Using molecular biotechnology, hybrid influenza virus strains were developed as vaccines using the H9N2 and H5N1 AI virus genes and six internal genes of human influenza viruses. Unlike the original H5N1 and H9N2 parent AI viruses, these hybrid vaccine viruses did not grow well in poultry and thus pose little threat of causing any damage to animal agriculture.
Technical Abstract: Two candidate formalin-inactivated vaccines, made from high-growth reassortant viruses with the HA and NA genes from avian viruses in a background of genes derived from A/Puerto Rico/8/34 (PR8), were prepared against H5N1 and H9N2 subtypes (designated as H5N1/PR8 and H9N2/PR8 respectively). These viruses bear the genotypes, antigenicity and attenuation in mouse models that are desirable in candidate vaccines. The pathogenicity of the newly generated avian-human reassortant vaccine viruses was also evaluated in chickens. Neither H5N1/PR8 nor H9N2/PR8 were highly pathogenic for chickens. No clinical signs, gross legions or histological lesions were observed in chickens that were administered H5N1/PR8 either intranasally (i.n.) or intravenously (i.v.) and virus was not detected in oropharyngeal or cloacal swabs. When H9N2/PR8 was administered i.n., no clinical signs, gross or histological lesions were observed and no virus was detected in cloacal swabs. However, virus was isolated at low titer from oropharyngeal swabs of all 8 chickens. Although no clinical signs were observed when H9N2/PR8 was administered i.v., mild tracheitis was seen in 1 of 2 chickens. Moderate amounts of antigen were observed in tracheal respiratory epithelium and low titers of virus were recovered from oropharyngeal and cloacal swabs of some chickens. In summary, both reassortant vaccine viruses replicated poorly in chickens. These studies suggest that these candidate vaccine viruses carry a low risk of transmission to chickens.