Leishmania vaccine development: exploiting the host-vector-parasite interface

Abstract

Visceral leishmaniasis (VL) is a disease transmitted by phlebotomine sand flies, fatal if untreated, and with no available human vaccine. In rodents, cellular immunity to Leishmania parasite proteins as well as salivary proteins of the sand fly is associated with protection, making them worthy targets for further exploration as vaccines. This review discusses the notion that a combination vaccine including Leishmania and vector salivary antigens may improve vaccine efficacy by targeting the parasite at its most vulnerable stage just after transmission. Furthermore, we put forward the notion that better modeling of natural transmission is needed to test efficacy of vaccines. For example, the fact that individuals living in endemic areas are exposed to sand fly bites and will mount an immune response to salivary proteins should be considered in pre-clinical and clinical evaluation of leishmaniasis vaccines. Nevertheless, despite remaining obstacles there is good reason to be optimistic that safe and effective vaccines against leishmaniasis can be developed.

Keywords: Leishmania; adjuvant; saliva; sand fly; vaccine.

Figure 1

Leishmania species are inoculated into the skin together with vector-derived factors after an infected sand fly bite where they infect macrophages and form skin lesions (cutaneous forms) or migrate, typically to the spleen, liver, and bone marrow (visceral forms).

Figure 2

(1) Immunizing with sand fly salivary proteins induces a T_H1 delayed type hypersensitivity response specific to the salivary protein (2) recalled to the bite site after the sand fly deposits parasites and salivary proteins while feeding where it activates nearby macrophages and (3) promotes Leishmania-specific immunity.