There is now an increasingly solid body of scientific evidence which demonstrates that the binding of small molecular weight compounds, peptides and antibodies (Abs) to fusion-intermediate conformations of gp41 leads to an inhibition of HIV cell entry. The principal aim of this project is to exploit this information by establishing a platform where gp41-derived vaccine candidates will be designed to elicit neutralising Abs. Several families of immunogens which mimic gp41 in its fusion intermediate conformations are already available and others will be designed using modelisation approaches. Candidates will be submitted to a thorough biophysical characterisation followed by a preclinical development in order to identify the most promising for clinical evaluation. A crucial selection parameter is the capacity of antigens to elicit neutralising Abs using internationally standardized assays. Since sexual transmission accounts for more than 90% of HIV infection, the capacity of Abs to inhibit infection at the mucosal level will also be determined.

Universidad de Granada