Characterization of a trimeric MPER containing HIV-1 gp41 antigen

被引:30
作者
Hinz, Andreas [1 ]
Schoehn, Guy [1 ,2 ]
Quendler, Heribert [3 ]
Hulsik, David Lutje [1 ]
Stiegler, Gabi [3 ]
Katinger, Hermann [3 ]
Seaman, Michael S. [5 ]
Montefiori, David [4 ]
Weissenhorn, Winfried [1 ]
机构
[1] UJF EMBL CNRS, UMI 3265, Unit Virus Host Cell Interact, F-38042 Grenoble 9, France
[2] CEA CNRS UJF, Inst Biol Struct Jean Pierre Ebel, UMR 5075, F-38027 Grenoble 1, France
[3] Univ Nat Resources & Appl Life Sci, Dept Biotechnol, Inst Appl Microbiol, A-1190 Vienna, Austria
[4] Duke Univ, Med Ctr, Lab AIDS Res & Dev, Dept Surg, Durham, NC 27705 USA
[5] Beth Israel Deaconess Med Ctr, Div Viral Pathogenesis, Boston, MA 02215 USA
关键词
HIV-1; gp41; mAb; 2F5; 4E10; Membrane fusion; HUMAN-IMMUNODEFICIENCY-VIRUS; PROXIMAL EXTERNAL REGION; HUMAN MONOCLONAL-ANTIBODY; BROADLY NEUTRALIZING ANTIBODIES; STRUCTURAL BASIS; TYPE-1; ANTIBODY; MEMBRANE-FUSION; TRANSMEMBRANE GLYCOPROTEIN; VACCINE DESIGN; ANTI-GP41; 2F5;
D O I
10.1016/j.virol.2009.05.015
中图分类号
Q93 [微生物学];
学科分类号
071005 ; 100705 ;
摘要
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. (C) 2009 Elsevier Inc. All rights reserved.
引用
收藏
页码:221 / 227
页数:7
相关论文
共 68 条
[1]   Human immunodeficiency virus type 1 gp41 antibodies that mask membrane proximal region epitopes: Antibody binding kinetics, induction, and potential for regulation in acute infection [J].
Alam, S. Munir ;
Scearce, Richard M. ;
Parks, Robert J. ;
Plonk, Kelly ;
Plonk, Steven G. ;
Sutherland, Laura L. ;
Gorny, Miroslaw K. ;
Zolla-Pazner, Susan ;
VanLeeuwen, Stacie ;
Moody, M. Anthony ;
Xia, Shi-Mao ;
Montefiori, David C. ;
Tomaras, Georgia D. ;
Weinhold, Kent J. ;
Karim, Salim Abdool ;
Hicks, Charles B. ;
Liao, Hua-Xin ;
Robinson, James ;
Shaw, George M. ;
Haynes, Barton F. .
JOURNAL OF VIROLOGY, 2008, 82 (01) :115-125
[2]   The role of antibody polyspecificity and lipid reactivity in binding of broadly neutralizing anti-HIV-1 envelope human monoclonal antibodies 2F5 and 4E10 to glycoprotein 41 membrane proximal envelope epitopes [J].
Alam, S. Munir ;
McAdams, Mildred ;
Boren, David ;
Rak, Michael ;
Scearce, Richard M. ;
Gao, Feng ;
Camacho, Zenaido T. ;
Gewirth, Daniel ;
Kelsoe, Garnett ;
Chen, Pojen ;
Haynes, Barton F. .
JOURNAL OF IMMUNOLOGY, 2007, 178 (07) :4424-4435
[3]   Structural analysis of the epitope of the Anti-HIV antibody 2F5 sheds light into its mechanism of neutralization and HIV fusion [J].
Barbato, G ;
Bianchi, E ;
Ingallinella, P ;
Hurni, WH ;
Miller, MD ;
Cilibertol, G ;
Cortese, R ;
Bazzo, R ;
Shiver, JW ;
Pessi, A .
JOURNAL OF MOLECULAR BIOLOGY, 2003, 330 (05) :1101-1115
[4]   Profiling the Specificity of Neutralizing Antibodies in a Large Panel of Plasmas from Patients Chronically Infected with Human Immunodeficiency Virus Type 1 Subtypes B and C [J].
Binley, James M. ;
Lybarger, Elizabeth A. ;
Crooks, Emma T. ;
Seaman, Michael S. ;
Gray, Elin ;
Davis, Katie L. ;
Decker, Julie M. ;
Wycuff, Diane ;
Harris, Linda ;
Hawkins, Natalie ;
Wood, Blake ;
Nathe, Cory ;
Richman, Douglas ;
Tomaras, Georgia D. ;
Bibollet-Ruche, Frederic ;
Robinson, James E. ;
Morris, Lynn ;
Shaw, George M. ;
Montefiori, David C. ;
Mascola, John R. .
JOURNAL OF VIROLOGY, 2008, 82 (23) :11651-11668
[5]   Redox-triggered infection by disulfide-shackled human immunodeficiency virus type 1 pseudovirions [J].
Binley, JM ;
Cayanan, CS ;
Wiley, C ;
Schülke, N ;
Olson, WC ;
Burton, DR .
JOURNAL OF VIROLOGY, 2003, 77 (10) :5678-5684
[6]   Cross-clade neutralization patterns among HIV-1 strains from the six major clades of the pandemic evaluated and compared in two different models [J].
Brown, Bruce K. ;
Wieczorek, Lindsay ;
Sanders-Buell, Eric ;
Borges, Andrew Rosa ;
Robb, Merlin L. ;
Birx, Deborah L. ;
Michael, Nelson L. ;
McCutchan, Francine E. ;
Polonis, Victoria R. .
VIROLOGY, 2008, 375 (02) :529-538
[7]   Monoclonal antibodies to phosphatidylinositol phosphate neutralize human immunodeficiency virus type 1: Role of phosphate-binding subsites [J].
Brown, Bruce K. ;
Karasavvas, Nicos ;
Beck, Zoltan ;
Matyas, Gary R. ;
Birx, Deborah L. ;
Polonis, Victoria R. ;
Alving, Carl R. .
JOURNAL OF VIROLOGY, 2007, 81 (04) :2087-2091
[8]   Structure-function analysis of the epitope for 4E10, a broadly neutralizing human immunodeficiency virus type 1 antibody [J].
Brunel, FM ;
Zwick, MB ;
Cardoso, RMF ;
Nelson, JD ;
Wilson, IA ;
Burton, DR ;
Dawson, PE .
JOURNAL OF VIROLOGY, 2006, 80 (04) :1680-1687
[9]   Immunization with recombinant canarypox vectors expressing membrane-anchored glycoprotein 120 followed by glycoprotein 160 boosting fails to generate antibodies that neutralize R5 primary isolates of human immunodeficiency virus type 1 [J].
Bures, R ;
Gaitan, A ;
Zhu, TF ;
Graziosi, C ;
McGrath, KM ;
Tartaglia, J ;
Caudrelier, P ;
EL Habib, R ;
Klein, M ;
Lazzarin, A ;
Stablein, DM ;
Deers, M ;
Corey, L ;
Greenberg, ML ;
Schwartz, DH ;
Montefiori, DC .
AIDS RESEARCH AND HUMAN RETROVIRUSES, 2000, 16 (18) :2019-2035
[10]   EFFICIENT NEUTRALIZATION OF PRIMARY ISOLATES OF HIV-1 BY A RECOMBINANT HUMAN MONOCLONAL-ANTIBODY [J].
BURTON, DR ;
PYATI, J ;
KODURI, R ;
SHARP, SJ ;
THORNTON, GB ;
PARREN, PWHI ;
SAWYER, LSW ;
HENDRY, RM ;
DUNLOP, N ;
NARA, PL ;
LAMACCHIA, M ;
GARRATTY, E ;
STIEHM, ER ;
BRYSON, YJ ;
CAO, YZ ;
MOORE, JP ;
HO, DD ;
BARBAS, CF .
SCIENCE, 1994, 266 (5187) :1024-1027