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Journal of Virology, October 1999, p. 8303-8307, Vol. 73, No. 10
0022-538X/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.

Avirulent Avian Influenza Virus as a Vaccine Strain against a Potential Human Pandemic

Ayato Takada,1 Noritaka Kuboki,1 Katsunori Okazaki,1 Ai Ninomiya,1 Hiroko Tanaka,1 Hiroichi Ozaki,1 Shigeyuki Itamura,2 Hidekazu Nishimura,2 Masayoshi Enami,3 Masato Tashiro,4 Kennedy F. Shortridge,5 and Hiroshi Kida1,*

Department of Disease Control, Graduate School of Veterinary Medicine, Hokkaido University, Sapporo 060-0818,1 Department of Virology 1, National Institute of Infectious Diseases, Shinjuku, Tokyo 162-8640,2 Department of Biochemistry, Kanazawa University School of Medicine, Kanazawa, Ishikawa 920-0934,3 and Department of Viral Disease and Vaccine Control, National Institute of Infectious Diseases, Musashimurayama, Tokyo 208-0011, 4Japan, and Department of Microbiology, The University of Hong Kong, Queen Mary Hospital, Hong Kong Special Administrative Region, People's Republic of China5

Received 8 April 1999/Accepted 14 July 1999

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 possibility of an incipient pandemic. However, it was not possible to prepare a vaccine against the virus in the conventional embryonated egg system because of the lethality of the virus for chicken embryos and the high level of biosafety therefore required for vaccine production. Alternative approaches, including an avirulent H5N4 virus isolated from a migratory duck as a surrogate virus, H5N1 virus as a reassortant with avian virus H3N1 and an avirulent recombinant H5N1 virus generated by reverse genetics, have been explored. All vaccines were formalin inactivated. Intraperitoneal immunization of mice with each of vaccines elicited the production of hemagglutination-inhibiting and virus-neutralizing antibodies, while intranasal vaccination without adjuvant induced both mucosal and systemic antibody responses that protected the mice from lethal H5N1 virus challenge. Surveillance of birds and animals, particularly aquatic birds, for viruses to provide vaccine strains, especially surrogate viruses, for a future pandemic is stressed.

* Corresponding author. Mailing address: Department of Disease Control, Graduate School of Veterinary Medicine, Hokkaido University, Sapporo 060-0818, Japan. Phone: (81-11) 706-5207. Fax: (81-11) 709-7259. E-mail: kida{at}vetmed.hokudai.ac.jp.

Journal of Virology, October 1999, p. 8303-8307, Vol. 73, No. 10
0022-538X/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.


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