The immunology of Leishmania infection and the implications for vaccine development

Abstract

Leishmania parasites are vector-borne protozoal pathogens found in tropical and subtropical regions of both the Old and New World. These parasites can cause visceral or cutaneous disease, and the pathology of the infection is determined by both host immune factors and species/strain differences of the parasite. Dogs are an important reservoir for maintaining the population of Leishmania parasites that can lead to visceral leishmaniasis in humans, and a vaccination approach may be an effective method for reducing the numbers of infected dogs. Resistance to leishmaniasis has been consistently associated with a T helper 1 immune response, characterized by the production of IFN-gamma by the antigen-specific lymphocyte population. The development of this Th1 response has been shown to be dependent upon both cytokines and dendritic cells during T cell activation. However, the development of a Leishmania vaccine effective in preventing these chronic diseases has proven to be a challenge. Vaccine trials have focused on whole-killed or subunit vaccines with adjuvants. Newer experimental strategies involve the attenuation of the Leishmania parasite via gene deletion technologies or the expression of specific Leishmania peptides within attenuated organisms, such as Bacillus Calmette Guérin. DNA vaccines and dendritic cell potentiators, such as CpG oligodeoxynucleotides and Flt-3 ligand, are also in the early stage of development. In addition, as part of blocking the transmission cycle of leishmaniasis, several laboratories are also exploring the possibility of immunomodulating the host toward the bite of the sand fly.