Oral Presentation Australian Society for Microbiology Annual Scientific Meeting 2013

Pulmonary immunisation against tuberculosis infection (#59)

Warwick J Britton 1 2 , E Tyne 1 , E P West 1 3 , K Chan 4 , I Atmosukarto 5 , J Stambas 6 , M Flórido 1
  1. Centenary Institute, University Of Sydney, Newtown, NSW, Australia
  2. Faculty of Medicine, University Of Sydney , Newtown, NSW, Australia
  3. University of Queensland, Brisbane, Queensland, Australia
  4. Faculty of Pharmacy, University of Sydney, Newtown, NSW, Sydney
  5. Lipotek P/L, Australian National University, Canberra, ACT, Australia
  6. Deakin University, Geelong, VIC, Australia

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.