Vaccines to prevent leishmaniasis

Abstract

Leishmaniasis is a parasitic disease that encompasses a range of clinical manifestations affecting people in tropical and subtropical regions of the world. Epidemiological and experimental data indicate that protection from disease can be achieved in most people. In addition, we know how the host immune system must respond to infection in order to control parasite growth. However, there is still no vaccine for use in humans. Here, we review our understanding of host immunity following Leishmania infection and also discuss recent advances in the development of vaccines to prevent leishmaniasis, highlighting a new promising approach that targets the parasite hemoglobin receptor.

Keywords: immunity; leishmania; parasites; vaccines.

Figure 1

Life cycle and transmission of Leishmania parasites. The promastigote form of Leishmania parasites responsible for human disease (VL, CL and MCL) are injected into the skin as a female sand fly takes a blood meal (1), and are then taken up by host macrophages (2). Promastigotes convert to the non-flagellated, amastigote form inside macrophages (3) and then divide by binary fission (4). The amastigotes are released by the rupture of macrophages (5) and can then be taken up by a female sand fly during another blood meal. The amastigote form then converts in the promastigote form in the midgut of the sand fly and can then again be transmitted to another human (anthroponotic transmission) or to animals that act as reservoirs (zoonotic transmission) (6).

Figure 2

The effect of HbR-DNA vaccination. (a) Mice and hamsters were vaccinated with the HbR-DNA vaccine before infection with L. donovani promastigotes (1). The antigens were presented by antigen-presenting cells (APC) to CD4⁺ and CD8⁺ T cells in context of MHC-II and MHC-I molecules, respectively (2). This led to the enhanced proliferation of both CD4⁺ and CD8⁺ T cells (3) and generation of multifunctional CD4⁺ and CD8⁺ T cells. CD4⁺ T cells enhanced antibody generation by B cells/plasma cells (4). The combined effect of increased multifunctional CD4⁺ and CD8⁺ T cells and antibody resulted in complete clearance of the parasite (5). (b) Non-vaccinated mice and hamsters were infected with L. donovani promastigotes (1). Antigens were presented by APC to CD4⁺ and CD8⁺ T cells, (2) which resulted in limited T-cell proliferation and the generation of interleukin-10 producing cells (3) leading to enhanced parasite growth (4).