title: Platform technology to generate broadly cross-reactive antibodies to α-helical epitopes in hemagglutinin proteins from influenza A viruses.
abstract: We have utilized a de novo designed two-stranded α-helical coiled-coil template to display conserved α-helical epitopes from the stem region of hemagglutinin (HA) glycoproteins of influenza A. The immunogens have all the surface-exposed residues of the native α-helix in the native HA protein of interest displayed on the surface of the two-stranded α-helical coiled-coil template. This template when used as an immunogen elicits polyclonal antibodies which bind to the α-helix in the native protein. We investigated the highly conserved sequence region 421-476 of HA by inserting 21 or 28 residue sequences from this region into our template. The cross-reactivity of the resulting rabbit polyclonal antibodies prepared to these immunogens was determined using a series of HA proteins from H1N1, H2N2, H3N2, H5N1, H7N7, and H7N9 virus strains which are representative of Group 1 and Group 2 virus subtypes of influenza A. Antibodies from region 449-476 were Group 1 specific. Antibodies to region 421-448 showed the greatest degree of cross-reactivity to Group 1 and Group 2 and suggested that this region has a great potential as a "universal" synthetic peptide vaccine for influenza A. © 2016 Wiley Periodicals, Inc. Biopolymers (Pept Sci) 106: 144-159, 2016.
authors.affiliation: Department of Biochemistry and Molecular Genetics, University of Colorado, Anschutz Medical Campus, School of Medicine, Aurora, CO, 80045.
authors.forename: Ziqing
authors.initials: Z
authors.lastname: Jiang
authors.affiliation: Department of Biochemistry and Molecular Genetics, University of Colorado, Anschutz Medical Campus, School of Medicine, Aurora, CO, 80045.
authors.forename: Lajos
authors.initials: L
authors.lastname: Gera
authors.affiliation: Department of Biochemistry and Molecular Genetics, University of Colorado, Anschutz Medical Campus, School of Medicine, Aurora, CO, 80045.
authors.forename: Colin T
authors.initials: CT
authors.lastname: Mant
authors.affiliation: Department of Biochemistry and Molecular Genetics, University of Colorado, Anschutz Medical Campus, School of Medicine, Aurora, CO, 80045.|Flagship Biosciences, Westminster, CO, 80021.
authors.forename: Brooke
authors.initials: B
authors.lastname: Hirsch
authors.affiliation: Department of Biochemistry and Molecular Genetics, University of Colorado, Anschutz Medical Campus, School of Medicine, Aurora, CO, 80045.|Molecular Cloning Laboratories (MCLAB), San Francisco, CA, 94080.
authors.forename: Zhe
authors.initials: Z
authors.lastname: Yan
authors.affiliation: Department of Biochemistry and Molecular Genetics, University of Colorado, Anschutz Medical Campus, School of Medicine, Aurora, CO, 80045.
authors.forename: Jonathan A
authors.initials: JA
authors.lastname: Shortt
authors.affiliation: Department of Biochemistry and Molecular Genetics, University of Colorado, Anschutz Medical Campus, School of Medicine, Aurora, CO, 80045.
authors.forename: David D
authors.initials: DD
authors.lastname: Pollock
authors.affiliation: Institute of Pathogen Biology at Chinese Academy of Medical Sciences, Yi Zhuang DiShengBeiLu, BeiGongDa RuanJianYuan, Bldg#7, Beijing, 100176, China.|Department of Immunology and Microbiology, University of Colorado, Anschutz Medical Campus, School of Medicine, Aurora, CO, 80045.
authors.forename: Zhaohui
authors.initials: Z
authors.lastname: Qian
authors.affiliation: Department of Immunology and Microbiology, University of Colorado, Anschutz Medical Campus, School of Medicine, Aurora, CO, 80045.
authors.forename: Kathryn V
authors.initials: KV
authors.lastname: Holmes
authors.affiliation: Department of Biochemistry and Molecular Genetics, University of Colorado, Anschutz Medical Campus, School of Medicine, Aurora, CO, 80045.
authors.forename: Robert S
authors.initials: RS
authors.lastname: Hodges
keywords: coiled-coil immunogens; helical epitopes; hemagglutinin; influenza A viruses; synthetic peptide vaccines