Immunity to vector saliva is compromised by short sand fly seasons in endemic regions with temperate climates

Individuals exposed to sand fly bites develop humoral and cellular immune responses to sand fly salivary proteins. Moreover, cellular immunity to saliva or distinct salivary proteins protects against leishmaniasis in various animal models. In Tbilisi, Georgia, an endemic area for visceral leishmaniasis (VL), sand flies are abundant for a short period of ≤3 months. Here, we demonstrate that humans and dogs residing in Tbilisi have little immunological memory to saliva of P. kandelakii, the principal vector of VL. Only 30% of humans and 50% of dogs displayed a weak antibody response to saliva after the end of the sand fly season. Likewise, their peripheral blood mononuclear cells mounted a negligible cellular immune response after stimulation with saliva. RNA seq analysis of wild-caught P. kandelakii salivary glands established the presence of a typical salivary repertoire that included proteins commonly found in other sand fly species such as the yellow, SP15 and apyrase protein families. This indicates that the absence of immunity to P. kandelakii saliva in humans and dogs from Tbilisi is probably caused by insufficient exposure to sand fly bites. This absence of immunity to vector saliva will influence the dynamics of VL transmission in Tbilisi and other endemic areas with brief sand fly seasons.