title: Characterization of a trimeric MPER containing HIV-1 gp41 antigen.
abstract: The membrane-proximal external region (MPER) of gp41 is considered as a prime target for the induction of neutralizing antibodies, since it contains the epitopes for three broadly neutralizing antibodies (2F5, 4E10 and Z13). Here we present a novel gp41 construct (HA-gp41) comprising gp41 HR2 and MPER fused to two triple-stranded coiled-coil domains at both ends. HA-gp41 is trimeric, has a high helical content in solution and forms rod-like structures as revealed by negative staining electron microscopy. Immunization of rabbits with HA-gp41 induced antibodies directed against MPER, which failed to exert significant neutralization capacity against envelopes from primary isolates. Thus trimerisation of MPER regions does not suffice to induce a potent neutralizing antibody response specific for conserved regions within gp41.
authors.affiliation: Unit for Virus Host Cell Interaction, UMI 3265 UJF-EMBL-CNRS, 6 rue Jules Horowitz, 38042 Grenoble cedex 9, France.
authors.forename: Andreas
authors.initials: A
authors.lastname: Hinz
authors.forename: Guy
authors.initials: G
authors.lastname: Schoehn
authors.forename: Heribert
authors.initials: H
authors.lastname: Quendler
authors.forename: David Lutje
authors.initials: DL
authors.lastname: Hulsik
authors.forename: Gabi
authors.initials: G
authors.lastname: Stiegler
authors.forename: Hermann
authors.initials: H
authors.lastname: Katinger
authors.forename: Michael S
authors.initials: MS
authors.lastname: Seaman
authors.forename: David
authors.initials: D
authors.lastname: Montefiori
authors.forename: Winfried
authors.initials: W
authors.lastname: Weissenhorn
mesh_terms: D016915:AIDS Vaccines / Q000737:chemistry / Q000235:genetics / Q000276:immunology*; D000595:Amino Acid Sequence; D000818:Animals; D000956:Antigens, Viral / Q000737:chemistry* / Q000235:genetics / Q000276:immunology*; D015483:HIV Antibodies / Q000097:blood; D015700:HIV Envelope Protein gp41 / Q000737:chemistry* / Q000235:genetics / Q000276:immunology*; D015497:HIV-1 / Q000737:chemistry / Q000276:immunology*; D046529:Microscopy, Electron, Transmission / Q000379:methods; D008969:Molecular Sequence Data; D009500:Neutralization Tests; D055503:Protein Multimerization; D020836:Protein Structure, Quaternary; D011817:Rabbits; D011994:Recombinant Proteins / Q000235:genetics / Q000276:immunology; D016415:Sequence Alignment
chemical_list: D016915:AIDS Vaccines; D000956:Antigens, Viral; D015483:HIV Antibodies; D015700:HIV Envelope Protein gp41; D011994:Recombinant Proteins; C514787:gp41 protein, Human immunodeficiency virus 1