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Journal of Virology, January 2007, p. 150-158, Vol. 81, No. 1
0022-538X/07/$08.00+0     doi:10.1128/JVI.01514-06
Copyright © 2007, American Society for Microbiology. All Rights Reserved.

Newcastle Disease Virus-Based Live Attenuated Vaccine Completely Protects Chickens and Mice from Lethal Challenge of Homologous and Heterologous H5N1 Avian Influenza Viruses{triangledown}

Jinying Ge,1 Guohua Deng,1 Zhiyuan Wen,1 Guobing Tian,1 Yong Wang,1 Jianzhong Shi,1 Xijun Wang,1 Yanbing Li,1 Sen Hu,1 Yongping Jiang,1 Chinglai Yang,2 Kangzhen Yu,1 Zhigao Bu,1* and Hualan Chen1*

National Key Laboratory of Veterinary Biotechnology and Animal Influenza Laboratory of the Ministry of Agriculture, Harbin Veterinary Research Institute, Chinese Academy of Agricultural Sciences, 427 Maduan Street, Harbin 150001, People's Republic of China,1 Department of Microbiology and Immunology, Emory University School of Medicine, Rollins Research Center, Atlanta, Georgia 303222

Received 15 July 2006/ Accepted 9 October 2006

H5N1 highly pathogenic avian influenza virus (HPAIV) has continued to spread and poses a significant threat to both animal and human health. Current influenza vaccine strategies have limitations that prevent their effective use for widespread inoculation of animals in the field. Vaccine strains of Newcastle disease virus (NDV), however, have been used successfully to easily vaccinate large numbers of animals. In this study, we used reverse genetics to construct a NDV that expressed an H5 subtype avian influenza virus (AIV) hemagglutinin (HA). Both a wild-type and a mutated HA open reading frame (ORF) from the HPAIV wild bird isolate, A/Bar-headed goose/Qinghai/3/2005 (H5N1), were inserted into the intergenic region between the P and M genes of the LaSota NDV vaccine strain. The recombinant viruses stably expressing the wild-type and mutant HA genes were found to be innocuous after intracerebral inoculation of 1-day-old chickens. A single dose of the recombinant viruses in chickens induced both NDV- and AIV H5-specific antibodies and completely protected chickens from challenge with a lethal dose of both velogenic NDV and homologous and heterologous H5N1 HPAIV. In addition, BALB/c mice immunized with the recombinant NDV-based vaccine produced H5 AIV-specific antibodies and were completely protected from homologous and heterologous lethal virus challenge. Our results indicate that recombinant NDV is suitable as a bivalent live attenuated vaccine against both NDV and AIV infection in poultry. The recombinant NDV vaccine may also have potential use in high-risk human individuals to control the pandemic spread of lethal avian influenza.

* Corresponding author. Mailing address: Harbin Veterinary Research Institute, CAAS, 427 Maduan Street, Harbin 150001, People's Republic of China. Phone for Zhigao Bu: 86-451-85935062. Fax: 86-451-82733132. E-mail: zgb{at}hvri.ac.cn. Phone for Hualan Chen: 86-451-85935079. Fax: 86-451-82761925. E-mail: hlchen1{at}yahoo.com.

{triangledown} Published ahead of print on 18 October 2006.

Journal of Virology, January 2007, p. 150-158, Vol. 81, No. 1
0022-538X/07/$08.00+0     doi:10.1128/JVI.01514-06
Copyright © 2007, American Society for Microbiology. All Rights Reserved.



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