Submitted to: Clinical and Vaccine Immunology
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 9/9/2007
Publication Date: 11/1/2007
Citation: Pappas, C., Matsuoka, Y., Swayne, D.E., Donis, R.O. 2007. Development and evaluation of an influenza subtype H7N2 vaccine candidate for pandemic preparedness. Clinical and Vaccine Immunology. 14(11):1425-1432. Interpretive Summary: Sporadic human infections by H7 avian influenza (AI) viruses have occurred in USA, Canada, and The Netherlands. As part of the global pandemic preparedness, a hybrid virus was developed using a North American lineage of H7N2 AI viruses for potential use in a human killed influenza vaccine. The vaccine virus when inoculated at high doses in mice and chickens grew in the respiratory system, but none of the animals became sick which is compatible with other low pathogenic AI viruses. In the mouse vaccine model, a killed vaccine made from the hybrid virus provided protection against Canadian and Dutch H7 high pathogenicity avian influenza viruses. These studies indicate that, H7 hybrid vaccine virus is immunogenic, safe and protective in animal models and has the potential for use as a human pandemic influenza vaccine.
Technical Abstract: Influenza virus of the H7N2 subtype is enzootic among some wild aquatic birds of North America. This virus has been introduced into non-commercial poultry in the United States. Virus circulation in poultry probably resulted in incidents of transmission of H7N2 virus to humans documented in 2002 and 2003, indicating that this virus could be considered a potential threat to public health if it acquired person-to-person transmissibility. A favored approach for global pandemic preparedness includes development of pre-pandemic vaccines for any potential pandemic virus, such as the North American lineage H7N2 avian viruses, leading to the establishment of a library of subtypes to be deployed in an emergency. To this end, we created a high growth reassortant virus (H7N2-PR8) containing the genes for the hemagglutinin (HA) and the neuraminidase (NA) from a low pathogenic A/Turkey/Virginia/4529/02 (H7N2) virus strain. The remaining six genes were derived from the human vaccine strain A/Johannesburg/82/96-PR8 (H1N1). The reassortant strain H7N2-PR8 was evaluated to assess its antigenicity, safety, and protective efficacy using mouse model. Antigenicity studies using ferret antibodies raised against H7N2-PR8 indicated that this virus confers broad cross-reactivity with divergent H7 viruses of different years and lineages. Mice and chickens inoculated with high doses of H7N2-PR8 supported virus replication but survived, indicating that this virus is comparable to other avian viruses of low pathogenicity. To assess the protective efficacy of H7N2-PR8, mice were immunized with two doses of formalin-inactivated A/H7N2-PR8, alone or with alum. Vaccinated mice subsequently challenged with highly pathogenic viruses from homologous and heterologous lineages, A/Canada/444/04 (H7N3) and A/Netherlands/219/03 (H7N7), revealed pronounced reduction of wild type virus replication. These studies indicate that, A/H7N2-PR8 is immunogenic, safe and protective in animal models; these are the essential attributes to qualify for Phase I human clinical trials as a pre-pandemic vaccine.