Pre-exposure to uninfected sand fly bites protects rhesus monkeys against cutaneous leishmaniasis (94.14)

Abstract Leishmaniasis is a vector-borne disease that distresses millions in the poorest regions of the globe. There are no anti-Leishmania vaccines approved for human use. Mice pre-exposed to uninfected sand fly bites (USFB) are protected against cutaneous leishmaniasis (CL). To test if pre-exposure to USFB protects rhesus monkeys against CL, we first developed a model where monkeys challenged with 50 L. major-infected Phlebotomus duboscqi sand flies developed self-healing cutaneous lesions mimicking human CL. In a following experiment, we exposed animals 3 times, every 21 days, to 20 uninfected P. duboscqi. We found that 70% of the monkeys reacted to USFB(DTH reaction and antibodies). Twenty-one days after the last exposure to USFB naïve, pre-exposed reactive (PE-R) and pre-exposed non-reactive monkeys were challenged with 50 L. major-infected P. duboscqi. We observed a reduction in disease burden and healing time in the PE-R group. This protection correlated with a two log reduction in parasite load and the PE-R animals showed a reduced maximum lesion diameter indicative of diminished disease. Skin biopsies two weeks post-infection showed a higher expression of IFN-γ in the PE-R group compared to naïve monkeys. Altogether, these data show that pre-exposure to uninfected P. duboscqi bites can protect monkeys against L. major infection. Identification of the salivary proteins responsible for the observed protection may lead to the discovery of vaccine candidates against human CL.