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Journal of Virology, July 2008, p. 6200-6208, Vol. 82, No. 13
0022-538X/08/$08.00+0     doi:10.1128/JVI.00187-08
Copyright © 2008, American Society for Microbiology. All Rights Reserved.

Comparative Efficacy of Neutralizing Antibodies Elicited by Recombinant Hemagglutinin Proteins from Avian H5N1 Influenza Virus

Chih-Jen Wei,^1, Ling Xu,^1, Wing-Pui Kong,¹ Wei Shi,¹ Kevin Canis,² James Stevens,^3, Zhi-Yong Yang,¹ Anne Dell,² Stuart M. Haslam,² Ian A. Wilson,³ and Gary J. Nabel^1*

Vaccine Research Center, NIAID, National Institutes of Health, Bldg. 40, Room 4502, MSC-3005, 40 Convent Drive, Bethesda, Maryland 20892-3005,¹ Division of Molecular Biosciences, Faculty of Natural Sciences, Imperial College London, London SW7 2AZ, United Kingdom,² Department of Molecular Biology & Skaggs Institute for Chemical Biology, The Scripps Research Institute, 10550 North Torrey Pines Road, BCC206, La Jolla, California 92037³

Received 25 January 2008/ Accepted 1 April 2008

Although the human transmission of avian H5N1 virus remains low, the prevalence of this highly pathogenic infection in avian species underscores the need for a preventive vaccine that can be made without eggs. Here, we systematically analyze various forms of recombinant hemagglutinin (HA) protein for their potential efficacy as vaccines. Monomeric, trimeric, and oligomeric H5N1 HA proteins were expressed and purified from either insect or mammalian cells. The immunogenicity of different recombinant HA proteins was evaluated by measuring the neutralizing antibody response. Neutralizing antibodies to H5N1 HA were readily generated in mice immunized with the recombinant HA proteins, but they varied in potency depending on their multimeric nature and cell source. Among the HA proteins, a high-molecular-weight oligomer elicited the strongest antibody response, followed by the trimer; the monomer showed minimal efficacy. The coexpression of another viral surface protein, neuraminidase, did not affect the immunogenicity of the HA oligomer, as expected from the immunogenicity of trimers produced from insect cells. As anticipated, HA expressed in mammalian cells without NA retained the terminal sialic acid residues and failed to bind 2,3-linked sialic acid receptors. Taken together, these results suggest that recombinant HA proteins as individual or oligomeric trimers can elicit potent neutralizing antibody responses to avian H5N1 influenza viruses.

Published ahead of print on 16 April 2008.

These authors contributed equally to this work.

Present address: Molecular Virology and Vaccines Branch, Influenza Division, NCIRD, CCID, Centers for Disease Control and Prevention, 1600 Clifton Rd., Mail stop G-16, Atlanta, GA 30333.