Chapter 9 : Designing HIV gp120 Peptide Vaccines: Rhetoric or Reality for Neuro-AIDS

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The majority of HIV subunit vaccines are based on the envelope proteins of HIV, namely, gp120 and gp 41, which form the gp160 glycoprotein complex, or on selected epitopes (immunogenic peptides) identified within these proteins. The focus of this chapter is to describe a novel strategy using comparative genomics to select a potential HIV-1 antigen (gp120). This novel approach has proven most promising for the subsequent screening of short peptides from HIV-1 gp120 antigen that are predicted to bind to a wide array of HLA alleles with a view toward the design of cocktail peptide vaccines. In the experimental model described in this chapter, the authors chopped the 510-residue segments of the gp120 envelope protein sequence into overlapping 9-residue-long peptides and then predicted the binding of all the peptides to 295 HLA-A alleles and 540 HLA-B alleles using T-Epitope Designer. The study model presented allowed the comparison of nine HIV-1 protein sequences with the protein sequences from the human genome, which showed that almost all HIV-1 proteins have some degree of sequence similarity to one or more human proteins. The viral diversity, together with host HLA variation in ethnic groups, sets the limit for peptide vaccine progress. The authors have outlined possible solutions to the issues using methods to predict appropriate T-cell epitopes and the rational design and synthesis of a highly conserved antigenic region of gp120. The experimental model described in the chapter serves as a framework for HIV-1 peptide vaccine design.

Citation: Kangueane P, Kayathri R, Sakharkar M, Flower D, Sadler K, Chiappelli F, Segal D, Shapshak P. 2009. Designing HIV gp120 Peptide Vaccines: Rhetoric or Reality for Neuro-AIDS, p 105-119. In Goodkin K, Shapshak P, Verma A (ed), The Spectrum of Neuro-AIDS Disorders. ASM Press, Washington, DC. doi: 10.1128/9781555815691.ch9
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Image of FIGURE 1.

Flowchart describing the comparison of HIV-1 proteins (NEF, REV, TAT, ENV, POL, VIF, VPR, VPU, and GAG) with the human proteins from genome projects and known structures from the PDB using BLASTP. NEF, REV, TAT, POL, and GAG have matching human HOMOLOGS in several pathways. This implies potential interference by HIV-1 proteins with the host pathways in infected individuals.

Citation: Kangueane P, Kayathri R, Sakharkar M, Flower D, Sadler K, Chiappelli F, Segal D, Shapshak P. 2009. Designing HIV gp120 Peptide Vaccines: Rhetoric or Reality for Neuro-AIDS, p 105-119. In Goodkin K, Shapshak P, Verma A (ed), The Spectrum of Neuro-AIDS Disorders. ASM Press, Washington, DC. doi: 10.1128/9781555815691.ch9
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Image of FIGURE 2.

The HIV-1 gp120 envelope protein was chopped into overlapping 9-mer peptides, and their binding with 296 A alleles and 540 B alleles was estimated using T-Epitope Designer. This procedure generated 28 peptide binders for 295 A alleles and 29 peptide binders for 540 B alleles in a combinatorial manner.

Citation: Kangueane P, Kayathri R, Sakharkar M, Flower D, Sadler K, Chiappelli F, Segal D, Shapshak P. 2009. Designing HIV gp120 Peptide Vaccines: Rhetoric or Reality for Neuro-AIDS, p 105-119. In Goodkin K, Shapshak P, Verma A (ed), The Spectrum of Neuro-AIDS Disorders. ASM Press, Washington, DC. doi: 10.1128/9781555815691.ch9
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Examples of HLA supertypes

Citation: Kangueane P, Kayathri R, Sakharkar M, Flower D, Sadler K, Chiappelli F, Segal D, Shapshak P. 2009. Designing HIV gp120 Peptide Vaccines: Rhetoric or Reality for Neuro-AIDS, p 105-119. In Goodkin K, Shapshak P, Verma A (ed), The Spectrum of Neuro-AIDS Disorders. ASM Press, Washington, DC. doi: 10.1128/9781555815691.ch9
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Immunogenicity and antigenicity of gp120 bridging-sheet mimetics

Citation: Kangueane P, Kayathri R, Sakharkar M, Flower D, Sadler K, Chiappelli F, Segal D, Shapshak P. 2009. Designing HIV gp120 Peptide Vaccines: Rhetoric or Reality for Neuro-AIDS, p 105-119. In Goodkin K, Shapshak P, Verma A (ed), The Spectrum of Neuro-AIDS Disorders. ASM Press, Washington, DC. doi: 10.1128/9781555815691.ch9

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