Innovative design of HIV vaccines and delivery systems for transcutaneous immunization

Funding: European Commission (FP7)
Duration: 1.1.2010 – 31.12.2015

Databases containing full-length sequences, experimentally identified T cell epitopes and protein structures from various HIV-1 isolates are readily available. Bioinformatic tools will be developed within this network to benefit from this vast amount of data in order to build novel GagPol variants representing universal HIV immunogens. For this, the proteins will be enriched with CD4- and CD8-epitopes epitopes from different clades while ensuring structural and functional preservation. Epitopes are selected preferentially if they are highly conserved among various HIV clades, known or predicted to be presented by frequent HLA haplotypes, or are observed in long-term nonprogressors. Furthermore a cellular display technology will be applied to screen libraries of native envelope derivatives in a membrane bound form against monoclonal neutralizing antibodies (Nabs) (compare VDAC project). This strategy will be adapted to screen envelope libraries based on CD4-independent envelopes, which have been shown to induce unusually high levels of bNabs (Zhang and Dimitrov, 2007). The optimized B- and T-cell immunogens formulated as protein, DNA, viral vectors or virus-like particles will finally be evaluated in transcutaneous immunizations.

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