Computer-assisted design, production and analysis of HIV-specific T-cell immunogens

Funding: Bavarian Research Foundation
Duration: 1.8.2009 – 31.10.2012

The protective phenotype of some HIV-positive long-term-non-progressors is associated with CTL responses against peptides presented on certain HLA alleles. As approaches to induce such responses by vaccination have failed so far, we want to generate epitope-enriched variants of the HIV Gag protein to achieve a broader immune response. For this, a computer-algorithm will be developed which (i) classifies CD8 T-cell epitopes previously identified in patients according to their immunological properties and (ii) incorporates a maximal number into Gag, (iii) ensuring structural and functional preservation. The performance of the algorithm will be validated experimentally by biochemical characterization of the epitope-enriched immunogen candidates. Finally, functional epitope-enriched Gag varaints will be immunologically characterized in human ex vivo model systems.

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