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filingDate 2007-06-26-04:00^^<http://www.w3.org/2001/XMLSchema#date>
publicationDate 2009-11-26-04:00^^<http://www.w3.org/2001/XMLSchema#date>
publicationNumber JP-2009541373-A
titleOfInvention Expansion of T cell repertoire containing subdominant epitopes by vaccination with antigen delivered as protein fragments or peptide cocktails
abstract The present invention provides for the prevention or treatment of chronic diseases by immunizing with a pool of overlapping peptides of the desired antigen (eg, 10-30 mer synthetic peptides with 2-20 amino acid overlap) in a suitable adjuvant. It teaches a simple method for inducing broad recognition of dominant and subdominant responses to epitopes of any given antigen that are important for. Not only does the T-cell repertoire be stimulated and the complete molecule is recognized when used for immunization and is induced by chronic infection, but it also includes a very broad spectrum of sub-dominant epitopes. It also induces a balanced response. The resulting T cell response to subdominant epitopes is important for protection against chronic diseases that concentrate and induce responses only to immunodominant epitopes. A major advantage of the present invention is that it expands the T cell repertoire, while requiring no prior knowledge of the precise location and nature of subdominant epitopes and recognition in the human population, thereby allowing several types of immune dominants. The point is to expand the total number of epitopes recognized by specific T cells stimulated by vaccination, from epitopes to multiple epitopes associated with the vaccine. For chronic diseases that are regulated by humoral immunity, the helper T cell response stimulated by the peptide mixture may be conveniently boosted with full length protein for maximum induction of the antibody response.
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