title: Comparative efficacy of neutralizing antibodies elicited by recombinant hemagglutinin proteins from avian H5N1 influenza virus.
abstract: 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 alpha2,3-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.
authors.affiliation: Vaccine Research Center, NIAID, National Institutes of Health, Bldg. 40, Room 4502, MSC-3005, 40 Convent Drive, Bethesda, MD 20892-3005, USA.
authors.forename: Chih-Jen
authors.initials: CJ
authors.lastname: Wei
authors.forename: Ling
authors.initials: L
authors.lastname: Xu
authors.forename: Wing-Pui
authors.initials: WP
authors.lastname: Kong
authors.forename: Wei
authors.initials: W
authors.lastname: Shi
authors.forename: Kevin
authors.initials: K
authors.lastname: Canis
authors.forename: James
authors.initials: J
authors.lastname: Stevens
authors.forename: Zhi-Yong
authors.initials: ZY
authors.lastname: Yang
authors.forename: Anne
authors.initials: A
authors.lastname: Dell
authors.forename: Stuart M
authors.initials: SM
authors.lastname: Haslam
authors.forename: Ian A
authors.initials: IA
authors.lastname: Wilson
authors.forename: Gary J
authors.initials: GJ
authors.lastname: Nabel
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D000914:Antibodies, Viral / Q000276:immunology*; D017931:DNA Primers / Q000235:genetics; D004797:Enzyme-Linked Immunosorbent Assay; D005822:Genetic Vectors / Q000235:genetics / Q000276:immunology; D019267:Hemagglutinin Glycoproteins, Influenza Virus / Q000235:genetics / Q000276:immunology*; D053124:Influenza A Virus, H5N1 Subtype / Q000235:genetics / Q000276:immunology*; D007252:Influenza Vaccines / Q000276:immunology*; D051379:Mice; D008969:Molecular Sequence Data; D011994:Recombinant Proteins / Q000276:immunology*
chemical_list: D000914:Antibodies, Viral; D017931:DNA Primers; D019267:Hemagglutinin Glycoproteins, Influenza Virus; D007252:Influenza Vaccines; D011994:Recombinant Proteins; C109963:hemagglutinin, avian influenza A virus