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Journal of Virology, November 2007, p. 11560-11568, Vol. 81, No. 21
0022-538X/07/$08.00+0     doi:10.1128/JVI.00713-07
Copyright © 2007, American Society for Microbiology. All Rights Reserved.

Immunization of Primates with a Newcastle Disease Virus-Vectored Vaccine via the Respiratory Tract Induces a High Titer of Serum Neutralizing Antibodies against Highly Pathogenic Avian Influenza Virus{triangledown}

Joshua M. DiNapoli,1 Lijuan Yang,1 Amorsolo Suguitan Jr.,1 Subbiah Elankumaran,2,{dagger} David W. Dorward,3 Brian R. Murphy,1 Siba K. Samal,2 Peter L. Collins,1 and Alexander Bukreyev1*

Laboratory of Infectious Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892,1 Virginia-Maryland Regional College of Veterinary Medicine, University of Maryland, College Park, Maryland 20742,2 Rocky Mountain Labs Research Technologies Section, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, Montana 598403

Received 3 April 2007/ Accepted 7 August 2007

The ongoing outbreak of highly pathogenic avian influenza virus (HPAIV) in birds, the incidence of transmission to humans with a resulting high mortality rate, and the possibility of a human pandemic warrant the development of effective human vaccines against HPAIV. We developed an experimental live-attenuated vaccine for direct inoculation of the respiratory tract based on recombinant avian Newcastle disease virus (NDV) expressing the hemagglutinin (HA) glycoprotein of H5N1 HPAIV (NDV-HA). Expression of the HPAIV HA gene slightly reduced NDV virulence, as evidenced by the increased mean embryo death time and reduced replication in chickens. NDV-HA was administered to African green monkeys in two doses of 2 x 107 infectious units each with a 28-day interval to evaluate the systemic and local antibody responses specific to H5N1 HPAIV. The virus was shed only at low titers from the monkeys, indicative of safety. Two doses of NDV-HA induced a high titer of H5N1 HPAIV-neutralizing serum antibodies in all of the immunized monkeys. Moreover, a substantial mucosal immunoglobulin A response was induced in the respiratory tract after one and two doses. The titers of neutralizing antibodies achieved in this study suggest that the vaccine would be likely to prevent mortality and reduce morbidity caused by the H5N1 HPAIV. In addition, induction of a local immune response in the respiratory tract is an important advantage that is likely to reduce or prevent transmission of the virus during an outbreak or a pandemic. This vaccine is a candidate for clinical evaluation in humans.

* Corresponding author. Mailing address: Laboratory of Infectious Diseases, NIAID, NIH, 50 South Dr., Rm. 6505, Bethesda, MD 20892. Phone: (301) 594-1854. Fax: (301) 496-8312. E-mail: ab176v{at}nih.gov

{triangledown} Published ahead of print on 22 August 2007.

{dagger} Present address: Virginia-Maryland Regional College of Veterinary Medicine Center for Molecular Medicine and Infectious Diseases, Virginia Polytechnic Institute and State University, Blacksburg, VA 24061.

Journal of Virology, November 2007, p. 11560-11568, Vol. 81, No. 21
0022-538X/07/$08.00+0     doi:10.1128/JVI.00713-07
Copyright © 2007, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Carnero, E., Li, W., Borderia, A. V., Moltedo, B., Moran, T., Garcia-Sastre, A. (2009). Optimization of Human Immunodeficiency Virus Gag Expression by Newcastle Disease Virus Vectors for the Induction of Potent Immune Responses. J. Virol. 83: 584-597 [Abstract] [Full Text]  
  • Collins, P. L., Bukreyev, A., Murphy, B. R. (2008). What Are the Risks--Hypothetical and Observed--of Recombination Involving Live Vaccines and Vaccine Vectors Based on Nonsegmented Negative-Strain RNA Viruses?. J. Virol. 82: 9805-9806 [Full Text]  
  • Han, G.-Z., Liu, X.-P., Li, S.-S. (2008). Caution about Newcastle Disease Virus-Based Live Attenuated Vaccine. J. Virol. 82: 6782-6782 [Full Text]  
  • Gao, Q., Park, M.-S., Palese, P. (2008). Expression of Transgenes from Newcastle Disease Virus with a Segmented Genome. J. Virol. 82: 2692-2698 [Abstract] [Full Text]  


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