Final Report Summary - Vaccines4TB (Genome- and HLA- wide scanning and validation of cytotoxic CD8 T cell responses against Mycobacterium tuberculosis)
Vaccines against tuberculosis are urgently needed. CD4 T cell responses play a major role in the generation of acquired immunity against Mycobacterium tubercolosis. The object of 'Genome- and HLA- wide scanning and validation of cytotoxic CD8 T cell responses against Mycobacterium tuberculosis' (Vaccines4TB) is to perform a complete antigen-and epitope-discovery of relevance for human immune CTL responses against Mycobacterium tuberculosis. Focusing on HLA class I restricted CTL constitutes the major risk involved in this project. The projects general goal was to generate a European genomics/proteomics based platform for antigen and epitope discovery, and specifically to test it in the development of vaccines and immunotherapy.
The project has discovered 129 epitopes of which 71 are HLA-A2-, 17 HLA-A3-, and 41 HLA-B7 -restricted peptides. Moreover, the project has generated a high quality shotgun expression, library representing the whole genome of the MTB-strain H37Rv and used it to screen blood samples. Using this method, 37 different antigens could be identified and characterised. In the last year of the project, the project has performed in vivo immunisation studies in HLA-A2 transgenic mice, investigating immune recognition of the most promising HLA-A2 binding Mtb peptides. The results obtained in this project provide new target epitopes for the development of vaccines against TB.
The project has discovered 129 epitopes of which 71 are HLA-A2-, 17 HLA-A3-, and 41 HLA-B7 -restricted peptides. Moreover, the project has generated a high quality shotgun expression, library representing the whole genome of the MTB-strain H37Rv and used it to screen blood samples. Using this method, 37 different antigens could be identified and characterised. In the last year of the project, the project has performed in vivo immunisation studies in HLA-A2 transgenic mice, investigating immune recognition of the most promising HLA-A2 binding Mtb peptides. The results obtained in this project provide new target epitopes for the development of vaccines against TB.
