Objectif HIV infection is one of the major global health problems of our times and one of the main priority research areas in EU policy for the FP6 program. Although natural immune control of HIV infection can occur, vaccine development has been hindered by difficulties in identifying what immune responses need to be induced. HIV-specific cytotoxic T lymphocyte (CTL) activity plays a central role in control of HIV.Thus, great variability exists between different CTL in their effectiveness. Recent studies have shown that MHC class I alleles (such as HLA-B57 in HIV infection) are associated with very successful control of viral replication. The dominant epitope targeted by B57-positive subjects is a peptide in p24 Gag, sequence TSTLQEQIAW (Gag residues 240-249), and in the great majority of cases the virus escapes recognition by CTL as a result of a mutation at residue 242 from ThrAsn (T242N).However, control of HIV is still maintained well. Subsequent works of Dr. Prado has shown that a contributing factor to this sustained control of HIV by B57-positive subjects is the fact that this T242N mutation inflicts a cost to viral replicative capacity. Thus, immune control of a now attenuated HIV is achieved more readily by remaining B57-restricted CTL responses.These studies together with further preliminary work indicate the importance of this mechanism of immune control. The main objectives of the proposal will be: to define further the CTL responses that are effective in control of HIV, and to explore the escape mutation s that inflict a significant cost to viral replicative capacity.These objectives will be achieved with the incorporation of Dr Prado to the host institution to integrate her previous knowledge into a new research field. This information will be of direct relevance to vaccine design, and these data will indicate which CTL responses need to be induced by a vaccine. Champ scientifique sciences naturellessciences biologiquesmicrobiologievirologiesciences médicales et de la santémédecine fondamentaleimmunologiesciences médicales et de la santésciences de la santémaladie infectieusevirus à ARNVIHsciences médicales et de la santémédecine fondamentalepharmacologie et pharmacieproduit pharmaceutiquevaccinssciences naturellessciences biologiquesgénétiquemutation Mots‑clés CTLS HIV delay in progression to AIDs fitness cost immunologic response vaccine design Programme(s) FP6-MOBILITY - Human resources and Mobility in the specific programme for research, technological development and demonstration "Structuring the European Research Area" under the Sixth Framework Programme 2002-2006 Thème(s) MOBILITY-2.1 - Marie Curie Intra-European Fellowships (EIF) Appel à propositions FP6-2005-MOBILITY-5 Voir d’autres projets de cet appel Régime de financement EIF - Marie Curie actions-Intra-European Fellowships Coordinateur THE CHANCELLOR, MASTERS AND SCHOLARS OF THE UNIVERSITY OF OXFORD Adresse University offices, wellington square Oxford Royaume-Uni Voir sur la carte Liens Site web Opens in new window Contribution de l’UE Aucune donnée
