Figures & data
Figure 1 An overview of the immune processes targeted by rBCG strain to improve anti-mycobacterial immunity. Professional antigen presenting cells (APC), such as dendritic cells, can present peptide fragments to CD8+ and CD4+ T cells, and induction of autophagy can improve this process (BCG:Ag85B). T cells can be expanded in the presence of IL-2 (BCG:IL-2), and numbers of antigen-specific cells can be increased by overexpression of protective antigens in BCG, such as Ag85B (BCG:Ag85B). APC-derived cytokines such as IL-12 and IL-18 (BCG:IL-18) can enhance the expansion of ‘Th1-like’ T cells secreting IFNγ and TNF, which can then act on infected host cells to aid elimination of ingested mycobacteria (BCG:IFNγ, BCG:TNF). The generation and maintenance of antigen-specific memory T cells can be improved by cytokines such as IL-15 (BCG-Ag85B-IL-15). Growth factors including GM-CSF and Flt3L can induce differentiation and activation of APCs and host cells such as macrophages to improve antigen presentation and aid destruction of internalized bacteria (BCG:GM-CSF, BCGFlt3L), while increased apoptosis of host cells can facilitate antigen transfer to APC and improve T cell presentation (BCG:LLO). Many of the cytokines and cell types described have additional roles/functions which are not depicted here. This schematic is only a representation of the vaccine strategies employed, a more comprehensive outline is provided in the text.
