The effector mechanism and vaccination against cutaneous leishmaniasis.

This paper summarises the recent findings that nitric oxide plays an important role in the elimination of intracellular and extracellular leishmania parasite in vitro and in vivo. Nitric oxide is produced by macrophages which are activated by IFN-gamma secreted from Th1 subsets of T cells. It is now believed that, at least in cutaneous leishmaniasis, Th2 subsets of CD4+ T cells are disease-promoting and they do so probably by producing IL-3 and IL-4 which inhibits the activation of macrophages by IFN-gamma. Thus, an effective anti-leishmania vaccine should aim at preferentially inducing Th1 subsets of T cells. Attention has been focused on the major surface glycoprotein, gp63, and the gene encoding this molecule has recently been cloned and sequenced. A peptide corresponding to the highly conserved zinc-binding region of the molecule was found to induce Th1 cells and significantly enhanced resistance to the disease. Furthermore, mice immunised orally with Salmonella typhimurium AroA- mutant carrying plasmids containing gp63 gene developed significant resistance to L. major infection. This may serve as a prototype oral leishmania vaccine.