Leishmaniasis: current status of vaccine development

Abstract

Leishmaniae are obligatory intracellular protozoa in mononuclear phagocytes. They cause a spectrum of diseases, ranging in severity from spontaneously healing skin lesions to fatal visceral disease. Worldwide, there are 2 million new cases each year and 1/10 of the world's population is at risk of infection. To date, there are no vaccines against leishmaniasis and control measures rely on chemotherapy to alleviate disease and on vector control to reduce transmission. However, a major vaccine development program aimed initially at cutaneous leishmaniasis is under way. Studies in animal models and humans are evaluating the potential of genetically modified live attenuated vaccines, as well as a variety of recombinant antigens or the DNA encoding them. The program also focuses on new adjuvants, including cytokines, and delivery systems to target the T helper type 1 immune responses required for the elimination of this intracellular organism. The availability, in the near future, of the DNA sequences of the human and Leishmania genomes will extend the vaccine program. New vaccine candidates such as parasite virulence factors will be identified. Host susceptibility genes will be mapped to allow the vaccine to be targeted to the population most in need of protection.

FIG. 1

World map highlighting areas where cutaneous, visceral, and mucocutaneous leishmaniasis is endemic.

FIG. 2

Schematic diagram of the Leishmania digenetic life cycle.

FIG. 3

Schematic representation of the immune regulation by Th cell types, the cytokines they produce, and their effects on immune responses. These cytokines are classified as type 1, type 2, or shared. Type 1 and type 2 cytokines activate different types of effector cells and lead to different responses. Abbreviations: LT-α, lymphotoxin alpha; GM-CSF, granulocyte-macrophage colony-stimulating factor; IgG and IgE, immunoglobulins G and E. Adapted from reference with permission from the publisher.