Characterization of a trimeric MPER containing HIV-1 gp41 antigen.
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.
Hinz
Andreas
A
Unit for Virus Host Cell Interaction, UMI 3265 UJF-EMBL-CNRS, 6 rue Jules Horowitz, 38042 Grenoble cedex 9, France.
Schoehn
Guy
G
Quendler
Heribert
H
Hulsik
David Lutje
DL
Stiegler
Gabi
G
Katinger
Hermann
H
Seaman
Michael S
MS
Montefiori
David
D
Weissenhorn
Winfried
W
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
D016915:AIDS Vaccines; D000956:Antigens, Viral; D015483:HIV Antibodies; D015700:HIV Envelope Protein gp41; D011994:Recombinant Proteins; C514787:gp41 protein, Human immunodeficiency virus 1