Avirulent avian influenza virus as a vaccine strain against a potential human pandemic

In the influenza H5N1 virus incident in Hong Kong in 1997, viruses that are closely related to H5N1 viruses initially isolated in a severe outbreak of avian influenza in chickens were isolated from humans, signaling the possi bility of an incipient pandemic. However, it was not possible to prepare a vaccine against the virus in the conventional embryonated egg system becaus e of the lethality of the virus for chicken embryos and the high level of b iosafety therefore required for vaccine production. Alternative approaches, including an avirulent H5N4 virus isolated from a migratory duck as a surr ogate virus, H5N1 virus as a reassortant with avian virus H3N1 and an aviru lent recombinant H5N1 virus generated by reverse genetics, have been explor ed. All vaccines were formalin inactivated. Intraperitoneal immunization of mice with each of vaccines elicited the production of hemagglutination-inh ibiting and virus-neutralizing antibodies, while intranasal vaccination wit hout adjuvant induced both mucosal and systemic antibody responses that pro tected the mice from lethal H5N1 virus challenge. Surveillance of birds and animals, particularly aquatic birds, for viruses to provide vaccine strain s, especially surrogate viruses, for a future pandemic is stressed.