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Journal of Virology, November 2008, p. 11374-11382, Vol. 82, No. 22
0022-538X/08/$08.00+0     doi:10.1128/JVI.01176-08
Copyright © 2008, American Society for Microbiology. All Rights Reserved.

Pathogenicity and Vaccine Efficacy of Different Clades of Asian H5N1 Avian Influenza A Viruses in Domestic Ducks {triangledown}

Jeong-Ki Kim,1 Patrick Seiler,1 Heather L. Forrest,1 Alexey M. Khalenkov,1 John Franks,1 Mahesh Kumar,2 William B. Karesh,3 Martin Gilbert,3 R. Sodnomdarjaa,4 Bounlom Douangngeun,5 Elena A. Govorkova,1 and Robert G. Webster1,6*

Division of Virology, Department of Infectious Diseases, St. Jude Children's Research Hospital, Memphis, Tennessee 38105,1 Division of Wyeth, Fort Dodge Animal Health, Fort Dodge, Iowa 50501,2 Field Veterinary Program, Wildlife Conservation Society, Bronx, New York 10460,3 State Central Veterinary Laboratory, Ulaanbaatar, Mongolia,4 National Animal Health Centre, Vientiane, Lao People's Democratic Republic,5 Department of Pathology, University of Tennessee, Health Science Center, Memphis, Tennessee 381066

Received 5 June 2008/ Accepted 2 September 2008

Waterfowl represent the natural reservoir of all subtypes of influenza A viruses, including H5N1. Ducks are especially considered major contributors to the spread of H5N1 influenza A viruses because they exhibit diversity in morbidity and mortality. Therefore, as a preventive strategy against endemic as well as pandemic influenza, it is important to reduce the spread of H5N1 influenza A viruses in duck populations. Here, we describe the pathogenicity of dominant clades (clades 1 and 2) of H5N1 influenza A viruses circulating in birds in Asia. Four representatives of dominant clades of the viruses cause symptomatic infection but lead to different profiles of lethality in domestic ducks. We also demonstrate the efficacy, cross-protectiveness, and immunogenicity of three different inactivated oil emulsion whole-virus H5 influenza vaccines (derived by implementing reverse genetics) to the viruses in domestic ducks. A single dose of the vaccines containing 1 µg of hemagglutinin protein provides complete protection against a lethal A/Duck/Laos/25/06 (H5N1) influenza virus challenge, with no evidence of morbidity, mortality, or shedding of the challenge virus. Moreover, two of the three vaccines achieved complete cross-clade or cross-subclade protection against the heterologous avian influenza virus challenge. Interestingly, the vaccines induce low or undetectable titers of hemagglutination inhibition (HI), cross-HI, and/or virus neutralization antibodies. The mechanism of complete protection in the absence of detectable antibody responses remains an open question.

* Corresponding author. Mailing address: Department of Infectious Diseases, St. Jude Children's Research Hospital, 262 Danny Thomas Place, Memphis, TN 38105-3678. Phone: (901) 595-3400. Fax: (901) 595-8559. E-mail: robert.webster{at}stjude.org

{triangledown} Published ahead of print on 10 September 2008.

Journal of Virology, November 2008, p. 11374-11382, Vol. 82, No. 22
0022-538X/08/$08.00+0     doi:10.1128/JVI.01176-08
Copyright © 2008, American Society for Microbiology. All Rights Reserved.



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