DOI: 10.1097/01.qai.0000351168.48843.5b

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Issn Print: 1525-4135

Publication Date: 2009/06/01


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212 In vivo alteration of humoral responses to HIV-1 envelope gp120 by antibodies to the CD4-binding site of gp120

Maria Luisa Visciano

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Excerpt

Background: The binding of antibodies (Abs) to the CD4-binding site (CD4bs) of gp120 has been shown to induce gp120 to undergo conformational changes that exposes and/or shields specific epitopes on this glycoprotein. Here we study alteration in the antigenicity and immunogenicity of gp120 when complexed with human monoclonal antibodies (mAbs) specific for the CD4 binding site of gp120.
Material and Methods: ELISA was used to assess changes in the antigenicity of gp120 when complexed with anti-CD4bs mAbs or with other anti-gp120 mAbs. To evaluate the immunogenicity of gp120/mAb complexes, BALB/c mice were inoculated with gp120/mAb complexes or with uncomplexed gp120 in RIBI adjuvant. The levels and specificities of serum anti-gp120 Ab responses induced in mice immunized with gp120/anti-CD4bs mAb complexes were compared to those in mice immunized with uncomplexed gp120 or other gp120/mAb complexes. Virus-neutralizing activities of the sera were also tested against HIV-1 isolates in the TZM-bl neutralization assay.
Results: The data demonstrate that the binding of anti-CD4bs mAb to gp120 specifically enhanced the reactivity of mAbs to the N-terminal C1 region and the neutralizing epitopes in the V3 loop. Importantly, immunization with gp120/anti-CD4bs mAb complexes consistently elicited higher levels of serum anti-gp120 Abs directed especially to the V3 region. Sera from mice immunized with gp120/anti-CD4bs mAb complexes also exhibited much more potent virus-neutralizing activity than sera of mice receiving uncomplexed gp120 or other gp120/mAb complexes, although the\ neutralizing activity was observed primarily against the homologous HIV-1 strain.

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