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doi:10.1016/j.virol.2004.08.037 
Published by Elsevier Inc.
Factors limiting the immunogenicity of HIV-1 gp120 envelope glycoproteins
Christoph Grundnera, b, Marie Pancerac, Joung-Mo Kanga, Markus Kocha, Joseph Sodroskia, b, d and Richard Wyatta, c, e, 
, 
Received 20 April 2004;
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Abstract
Efficient immune responses to HIV-1 gene products are essential elements to the development and design of an effective vaccine. Ideally, both humoral and cellular responses will be optimally elicited. It is therefore important to elucidate any factors that might limit the immunogenicity of HIV-1 proteins that are likely to be included in an effective vaccine. Since the HIV-1 exterior envelope glycoprotein gp120 is a major target for neutralizing antibodies, it is a virtual certainty that this gene product will be a component of any vaccine that seeks to elicit neutralizing antibody responses from the host humoral immune system. We report here the testing of several HIV-1 gp120 variants derived from a primary isolate that appears deficient in eliciting immune responses at both the level of CD4+ help and consequently in the generation of high-affinity IgG antibody responses in small animals. Factors limiting an effective immune response include (a) envelope glycoprotein strain variation decreasing functional T-cell help, (b) alteration of the glycosylation patterns of gp120 by expression in different cell types, and (c) the native structure of gp120 itself, which may limit the elicitation of effective T-cell help during natural infection or during parenteral immunization in adjuvant. Such limiting factors and others should be considered in the design and testing of gp120-based immunogens in small animals and possibly in primates as well.
Keywords: HIV-1; Envelope glycoproteins; Immunogenicity
Article Outline
- Introduction
- Results
- Anti-gp120 IgG reactivity in mouse sera raised against YU2 core+V3 gp120 and HXBc2 core+V3 gp120 glycoproteins with and without heterologous T-cell helper epitopes
- Serum reactivity against TH or neoepitopes
- Anti-gp120 IgG and IgM responses elicited by core+V3 gp120 and core+V3-TH gp120 in rabbits
- Anti-gp120 IgG reactivity in mouse sera raised against YU2 full-length gp120 and gp120-TH and ELISPOT data are consistent with a TH2 immune response
- Carbohydrate reactivity in sera raised against core+V3 gp120, core+V3 gp120-TH, full-length WTgp120, and WTgp120-TH in mice and rabbits
- Effects of adjuvant on the immunogenicity of full-length WTgp120 and WTgp120-TH produced in insect cells
- Comparison of anti-gp120 IgG titers raised against mammalian- and Drosophila-made full-length gp120
- Comparison of the anti-gp120 IgG titers elicited by native gp120 relative to denatured gp120
- Discussion
- Materials and methods
- Envelope glycoprotein constructs
- Production of recombinant envelope glycoprotein in Drosophila S2 cells
- Deglycosylation of YU2 core+V3 gp120 and WTgp120
- ELISA
- Splenocyte preparation
- Mouse IL-4 ELISPOT
- Denaturation of the YU2 gp120 and gp120-TH proteins and ELISA analysis
- Immunizations and serum preparation
- Acknowledgements
- Appendix A. Appendix
- References
