Abstract
Immunity to a sand fly salivary protein protects against visceral leishmaniasis (VL) in hamsters. This protection was associated with the development of cellular immunity in the form of a delayed-type hypersensitivity response and the presence of IFN-γ at the site of sand fly bites. To date, there are no data available regarding the cellular immune response to sand fly saliva in dogs, the main reservoirs of VL in Latin America, and its role in protection from this fatal disease. Two of 35 salivary proteins from the vector sand fly Lutzomyia longipalpis, identified using a novel approach termed reverse antigen screening, elicited strong cellular immunity in dogs. Immunization with either molecule induced high IgG2 antibody levels and significant IFN-γ production following in vitro stimulation of PBMC with salivary gland homogenate (SGH). Upon challenge with uninfected or infected flies, immunized dogs developed a cellular response at the bite site characterized by lymphocytic infiltration and IFN-γ and IL-12 expression. Additionally, SGH-stimulated lymphocytes from immunized dogs efficiently killed Leishmania infantum chagasi within autologous macrophages. Certain sand fly salivary proteins are potent immunogens obligatorily co-deposited with Leishmania parasites during transmission. Their inclusion in an anti-Leishmania vaccine would exploit anti-saliva immunity following an infective sand fly bite and set the stage for a protective anti-Leishmania immune response.
Highlights
Leishmaniasis is a vector-borne neglected disease transmitted exclusively by the bite of infected phlebotomine sand flies
Leishmaniasis is a vector-borne disease transmitted by sand fly bites where parasites are co-deposited with saliva into the wound
Our group has demonstrated that distinct molecules in the saliva of various sand fly species drive an immune response that protects experimental rodent models from self-healing cutaneous and fatal visceral leishmaniasis
Summary
Leishmaniasis is a vector-borne neglected disease transmitted exclusively by the bite of infected phlebotomine sand flies. Leishmaniasis presents with multiple clinical manifestations including cutaneous, mucocutaneous, diffuse and visceral (VL) infections. The latter is responsible for 59,000 deaths a year, a parasitic disease statistic surpassed only by malaria [4]. Zoonotic VL (ZVL) is wide spread and occurs in Latin America, Northern Africa, Southern Europe and areas of the Middle East and Asia [5,6,7]. There is a clear association between a high rate of infection in dogs and an increased risk of human disease [3]. An anti-Leishmania canine vaccine would protect dogs from a fatal disease but could have a considerable effect on reducing human infections
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