Pulmonary immunisation against tuberculosis infection (#59)
The current subunit vaccines being developed against tuberculosis (TB) rely on a relatively small subset of secreted proteins of Mycobacterium tuberculosis. We have investigated a number of other secreted and non-secreted proteins of M. tuberculosis as potential vaccines against TB. One of these is the M. tuberculosis secreted lipoprotein, MPT83, which as a protein or DNA vaccine induces protective immunity against M. tuberculosis. Pulmonary delivery of subunit vaccines may prove an efficient way for boosting anti-mycobacterial immunity induced by prior BCG immunisation. To investigate this, we have developed a dry powder vaccine based on MPT83 non-covalently linked to a novel TLR2 ligand, Lipokel (Lipotek). Delivery of this vaccine directly to the lungs activated antigen presenting cells in the lungs and draining lymph nodes and stimulated specific IFN- secreting T cell responses, which provided significant protection against aerosol M. tuberculosis infection. To examine whether induction of pulmonary CD4 and/or CD8 T cell responses are required for protection against acute M. tuberculosis infection, we generated recombinant Influenza A Virus (IAV) expressing M. tuberculosis epitopes. These rIAVs were highly immunogenic. Interestingly, the rIAV expressing the dominant CD4, but not the CD8, T cell epitope induced protective immunity against M. tuberculosis. The potential of the pulmonary route for immunisation against TB will be discussed.
Support: NHMRC.