Convergent combinatory peptide libraries and their use for vaccination against hepatitis c virus
OwnerBertrand Georges, Helene Gras-Masse +2inventors
InventorsBertrand Georges, Helene Gras-Masse, Ahmil Bouzidl, Claude Auriault
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Abstract
The invention relates to the design and synthesis of immunogenic peptides corresponding to restricted regions of virus proteins involving a T cell immune response and to convergent combinatory peptide libraries derived from said regions. The invention applies, in particular, to the hepatitis C virus and to the production of corresponding vaccinal preparations.
Claims9
Process for preparing immunogenic peptides corresponding to restricted regions of virus proteins involving a T cell immune response and to convergent combinatory peptide libraries derived from, said regions, characterized in that it includes:
- a) identifying sequences of amino acids constituting potential T epitopes, by predictive, non-experimental searching—for anchoring motifs for class II MHC molecules, from the native sequences of the proteins of the virus—and for areas having a high density of said anchoring motifs;
- b) designing convergent combinatory peptide libraries (termed “convertopes”), derived from the sequences of epitopes identified in a), by targeted substitution of amino acids at chosen positions, to induce non-natural degeneracy of each of the epitopes,
- on one hand, in order to increase the ability of the epitope to anchor to the class II MHC molecules,
- and, on the other hand, in order to broaden the repertory of recognition of the epitope by the T cell receptor;
- c) synthesizing
- on one hand, the peptides with native sequence chosen among the peptides as identified in a),
- and, on the other hand, the corresponding convertopes as identified in b).
Group of potential epitope sequences identified using the process according to claim la), including sequences ID Nos. 1 to 8 of the capsid protein, sequences ID Nos. 9 to 21 of the NS3 protein and sequences ID Nos. 22 to 26 of the NS4 protein of the HCV.
Dependencies are inferred from the claim text.