TB still ranks as one of the main causes of illness and mortality worldwide. There is therefore an urgent need for an effective vaccine against the causative bacillus, Mycobacterium tuberculosis (M. tuberculosis). To develop an effective vaccine, antigens and their epitopes capable of eliciting an appropriate immune response against the infection are required. Effects of mycobacteria can be neutralised by so-called CD8 cytotoxic T cells. Cytotoxic T cells (CTLs), otherwise known as killer or CD8 T cells, destroy cells that are infected with pathogens. Although effective against other mycobacteria, previous research had not identified many CTL responses against M. Tuberculosis. The aim of the EU-funded project 'Genome- and HLA- wide scanning and validation of cytotoxic CD8 T cell responses against Mycobacterium tuberculosis' (Vaccines4TB) was to identify proteins that stimulate an immune response against the bacterium. Project scientists focused on CTLs of the human leukocyte antigen (HLA) major histocompatability complex that encode antigen-presenting proteins. Two high-throughput screening methods were used. First, the 'forward antigen discovery' is a process where the whole M. tuberculosis genome is screened for encoded proteins that are targets for CTL responses. The second, the 'reverse antigen discovery' method selects, by computational means, proteins that are likely to contain CTL epitopes. These are then validated by binding to the HLA1 system and confirmed using CTL responses from TB patients. Vaccines4TB researchers discovered just short of 130 epitopes that fit the bill. Furthermore, the project also generated a complete library representing one particular strain of M. tuberculosis to screen blood samples. Immunisation studies using mice models were also performed using the two most promising epitopes. A European genomics/proteomics-based platform for antigen and epitope has been developed against TB. This represents a formidable framework for the development of new vaccines and immunotherapy to curb the bacterium's destructive course, particularly in third world countries.
Genome- and HLA- wide scanning and validation of cytotoxic CD8 T cell responses against Mycobacterium tuberculosis
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