Targeting a neutralizing epitope of HIV envelope Gp120 by immune complex vaccine

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Abstract

There are formidable challenges in developing HIV vaccines that elicit potent neutralizing antibodies against a broad array of HIV-1 isolates. The key targets for these neutralizing antibodies are the viral envelope antigens gp120 and gp41. Although broadly reactive neutralizing epitopes on gp120 and gp41 have been mapped and studied extensively, these epitopes are poorly immunogenic. Indeed, various vaccine candidates tested in preclinical and clinical trials do not generate antibodies against these epitopes. Hence, novel immunogen designs to augment the immunogenicity of these neutralizing epitopes are wanted. In this review, a unique immunogen design strategy that exploits immune complexes of gp120 and selected anti-gp120 monoclonal antibodies (mAb) to elicit neutralizing antibodies against cross-reactive V3 epitopes is discussed. The ability of these complexes to stimulate neutralizing antibodies is dictated by fine specificity and affinity of mAbs used to form the complexes, indicating the contribution of Fab-mediated activity, rather than conventional Fc-mediated enhancement. Further improvement of V3 immunogenicity is attainable by forming immune complexes with gp120 mutants lacking site-specific N-linked glycans. The increased V3 immunogenicity on the mutated gp120/mAb complexes correlates with enhancement of in vitro antibody recognition (antigenicity) and proteolytic resistance of V3 epitopes when presented on the complexes. These insights should provide guidelines for the development of more potent immunogens that target not only the prototypic V3 epitopes but also other broadly reactive epitopes on the HIV envelope.© 2012 Kumar R, et al.

Figures

  • Figure 1: Immune complex vaccine strategy utilizes Fab- and Fc-mediated activities to stimulate robust Ab response against targeted epitopes on gp120
  • Figure 2: Neutralizing antibody response elicited by uncomplexed gp120 versus gp120/mAb complexes
  • Figure 3: Complementary patterns of binding and neutralizing anti-V3 Abs generated by immune complexes made with gp120LAI versus gp120JRFL
  • Table 1: Immunological parameters of V3 epitopes presented on wild type or mutant gp120 on its own or as immune complexes with mAb 654-D.
  • Table 2: Approaches to further improve the potency and breadth of Ab responses elicited by immune complex vaccines.

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CITATION STYLE

APA

Kumar, R., Visciano, M. L., Li, H., & Hioe, C. (2012). Targeting a neutralizing epitope of HIV envelope Gp120 by immune complex vaccine. Journal of AIDS and Clinical Research. https://doi.org/10.4172/2155-6113.S8-002

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