Outbreaks of highly pathogenic H5N1 influenza viruses have been reported in many countries worldwide. The possibility of pandemics caused by H5N1 influenza viruses is high since human infections by H5N1 viruses continually occur. In this study we determined the immune response and efficacy of inactivated H5N1 vaccine developed by reverse genetics in ferrets. Ferrets intramuscularly inoculated with two doses of H5N1 vaccine survived the lethal challenge with homologous or heterologous H5N1 influenza viruses, while 75% and 25% of ferrets immunized with one dose of H5N1 vaccine survived the lethal challenge with homologous and heterologous H5N1 influenza viruses, respectively. When we determined antibody subtypes specific for H5N1 influenza viruses in tissues and sera of vaccinated ferrets, IgG antibodies were detected mainly in the trachea, nostril, lung, heart, liver, kidney, intestine, spleen, and serum. Our results suggest that IgG antibodies may play a major role in protecting ferrets immunized with the inactivated H5N1 vaccine from lethal challenge with H5N1 influenza viruses.
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