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Characterization of Antibody Responses Against the 2F5 Epitope ELDKWA Using HIV-1 Env-Mediated Membrane Fusion and Neutralization Assays

Characterization of Antibody Responses Against the 2F5 Epitope ELDKWA Using HIV-1 Env-Mediated Membrane Fusion and Neutralization Assays
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摘要 The epitope ELDKWA, which is located in the membrane-proximal external region (MPER) of HIV-1 gp41, is an important neutralizing epitope. The human monoclonal antibody (mAb) 2F5 against this epitope shows broad neutralizing activity toward many HIV strains. However, several reports have shown that the epitope-specific mAbs induced by peptides containing MPER did not exhibit the same neutralizing activities as human mAb 2F5. In this study, four ELDKWA epitope specific mAbs (9E7, 7E10, 6B5, and 2B4) induced by immunization with the ELDKWA epitope in varied molecular contexts, all showed inhibitory activi- ties with different potencies in HIV-1 Env-mediated membrane fusion assays and pseudovirus neutralization assays. This result indicates that though these antibodies recognize the epitope ELDKWA, their characteri- zations differ from that of neutralizing antibodies, implying that the neutralizing mAbs can be induced but also need to be screened, and the protective ability of a related vaccine antigen depends on the concentra- tion of the neutralizing mAbs in the induced polyclonal antibodies. The epitope ELDKWA, which is located in the membrane-proximal external region (MPER) of HIV-1 gp41, is an important neutralizing epitope. The human monoclonal antibody (mAb) 2F5 against this epitope shows broad neutralizing activity toward many HIV strains. However, several reports have shown that the epitope-specific mAbs induced by peptides containing MPER did not exhibit the same neutralizing activities as human mAb 2F5. In this study, four ELDKWA epitope specific mAbs (9E7, 7E10, 6B5, and 2B4) induced by immunization with the ELDKWA epitope in varied molecular contexts, all showed inhibitory activi- ties with different potencies in HIV-1 Env-mediated membrane fusion assays and pseudovirus neutralization assays. This result indicates that though these antibodies recognize the epitope ELDKWA, their characteri- zations differ from that of neutralizing antibodies, implying that the neutralizing mAbs can be induced but also need to be screened, and the protective ability of a related vaccine antigen depends on the concentra- tion of the neutralizing mAbs in the induced polyclonal antibodies.
作者 曹玥 陈应华
出处 《Tsinghua Science and Technology》 SCIE EI CAS 2010年第4期447-451,共5页 清华大学学报(自然科学版(英文版)
基金 Supported by the National High-Tech Research and Development (973) Program of China (No. 2006CB504203)
关键词 HIV-1 ELDKWA epitope monoclonal antibodies NEUTRALIZATION HIV-1 ELDKWA epitope monoclonal antibodies neutralization
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参考文献22

  • 1Muster T, Guinea R, Katinger H, et al. Cross-neutralizing antibodies against divergent human immunodeficiency virus type 1 isolates induced by the gp41 sequence ELDKWAS. J. Virol., 1994, 68: 4031-4034.
  • 2Muster T, Steindl F, Katinger H, et al. A conserved neutralizing epitope on gp41 of human immunodeficiency virus type 1. J. Virol., 1993, 67: 6642-6647.
  • 3Zwick M B, Labrijn A F, Burton D R, et al. Broadly neutralizing antibodies targeted to the membrane-proximal external region of human immunodeficiency virus type 1 glycoprotein gp41. J. Virol., 2001, 75:10 892-10 905.
  • 4Binley J M, Wrin T, Burton D R, et al. Comprehensive cross-clade neutralization analysis of a panel of anti-human immunodeficiency virus type 1 monoclonal antibodies. J. Virol., 2004, 78:13 232-13 252.
  • 5Ofek G, Tang M, Kwong P D, et al. Structure and mechanistic analysis of the anti-human immunodeficiency virus type 1 antibody 2F5 in complex with its gp41 epitope, J. Virol., 2004, 78:10 724-10 737.
  • 6Xiao Y, Zhao Y, Chen Y H, et al. Epitope-vaccine induces high levels of ELDKWA-epitope-specific neutralizing antibody. Immunol. lnvest., 2000, 29: 41-50.
  • 7Hoa J, MacDonald K S, Barber B H. Construction of recombinant targeting immunogens incorporating an HIV-1 neutralizing epitope into sites of differing conformational constraint. Vaccine, 2002, 20:1169-1180.
  • 8Coeffier E, Clement J M, Rojas M, et al. Antigenicity and immunogenicity of the HIV-1 gp41 epitope ELDKWA inserted into permissive sites of the Male protein. Vaccine, 2000, 19: 684-693.
  • 9McGaughey G B, Citron M, Htmai W M, et al. HIV-1 vaccine development: Constrained peptide immunogens show improved binding to the anti-H1V-1 gp41 MAb. Biochemistry, 2003, 42: 3214-3223.
  • 10Sun Z Y, Oh K J, Reinherz E L, et al. HIV-1 broadly neutralizing antibody extracts its epitope from a kinked gp41 ectodomain region on the viral membrane. Immunity, 2008, 28: 52-63.

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