Phlebotomus papatasisand fly salivary protein diversity and immune response potential in Egypt and Jordan populations

Abstract

24 Phlebotomus papatasi sand flies inject their hosts with a myriad of pharmacologically active 25 salivary proteins to assist with blood feeding and to modulate host defenses. These salivary 26 proteins have been studied for their role in cutaneous leishmaniasis disease outcome with 27 different salivary proteins attenuating or exacerbating lesion size. Studies have shown that while 28 co-administered sand fly saliva exacerbates Leishmania major infections in naïve mice, animals 29 pre-exposed to saliva are protected, with the infection attenuated via a delayed-type 30 hypersensitivity immune reaction. These studies highlight the potential of the salivary 31 components to be used as a vaccine. One protein in particular, P. papatasi salivary protein 15 32 (PpSP15) has been intensively studied because of its ability to protect mice against Le. major 33 challenge. The number of antigenic molecules included in vaccines is restricted thus 34 emphasizing the role of population genetics to identify molecules, like PpSP15, that are 35 functionally significant, conserved across populations and do not experience selection. Three 36 distinct ecotope study sites, one in Egypt (Aswan) and two in Jordan (Swaimeh and Malka), 37 were chosen based on their elevation, rainfall, vegetation, differing reservoir species, and the 38 presence or absence of Le. major. The objective of this work was to analyze the genetic 39 variability of nine of the most abundantly expressed salivary proteins including PpSP12, 40 PpSP14, PpSP28, PpSP29, PpSP30, PpSP32, PpSP36, PpSP42, and PpSP44 and to predict their 41 ability to elicit an immune response. Two proteins, PpSP12 and PpSP14, demonstrated low 42 genetic variability across the three sand fly populations represented in this study, with multiple 43 predicted MHCII epitope binding sites, identified by alleles present in the human populations 44 from the study sites. The other seven salivary proteins revealed greater allelic variation across 45 the same sand fly populations indicating that their use as vaccine targets may prove to be 46 challenging. 3 47 Author Summary 48 Phlebotomus papatasi sand flies vector Leishmania major parasites, one of the causative agents 49 of cutaneous leishmaniasis (CL). Approximately 0.7-1.2 million cases of CL occur each year. CL 50 produces disfiguring skin lesions for which no vaccine currently exists. Hematophagous vector 51 salivary proteins are pharmacologically active molecules that modulate inflammation, 52 vasoconstriction, and blood clotting for females that require a sanguineous meal for oviposition. 53 Salivary proteins from multiple phlebotomine sand fly species have been widely studied and 54 scrutinized to characterize their function in blood feeding facilitation as well as their ability to 55 exacerbate or attenuate Leishmania infections and their potential as vaccine candidates. A 56 successful sand fly salivary protein-based vaccine to combat CL largely depends on the genetic 57 variability, expression profiles, and human immune response to the ...

Genomic Analysis of Two Phlebotomine Sand Fly Vectors ofLeishmaniafrom the New and Old World

“…While previous studies demonstrated relatively low genetic differentiation between Ph. papatasi populations separated by large geographical distances [9,20], more recent studies have identified genetic differentiation between geographically separated populations [18, [21][22][23][24] and local differentiation [25]. Microsatellite analysis, in particular, revealed two distinct genetic clusters of Ph.…”