Phlebotomus papatasi sand fly predicted salivary protein diversity and immune response potential based on in silico prediction in Egypt and Jordan populations.

Phlebotomus papatasisand flies inject their hosts with a myriad of pharmacologically active salivary proteins to assist with blood feeding and to modulate host defenses. In addition, salivary proteins can influence cutaneous leishmaniasis disease outcome, highlighting the potential of the salivary components to be used as a vaccine. Variability of vaccine targets in natural populations influences antigen choice for vaccine development. Therefore, the objective of this study was to investigate the variability in the predicted protein sequences of nine of the most abundantly expressed salivary proteins from field populations, testing the hypothesis that salivary proteins appropriate to target for vaccination strategies will be possible.PpSP12,PpSP14,PpSP28,PpSP29,PpSP30,PpSP32,PpSP36,PpSP42,and PpSP44mature cDNAs from field collectedP.papatasifrom three distinct ecotopes in the Middle East and North Africa were amplified, sequenced, andin silicotranslated to assess the predicted amino acid variability. Two of the predicted sequences, PpSP12 and PpSP14, demonstrated low genetic variability across the three geographic isolated sand fly populations, with conserved multiple predicted MHCII epitope binding sites suggestive of their potential application in vaccination approaches. The other seven predicted salivary proteins revealed greater allelic variation across the same sand fly populations, possibly precluding their use as vaccine targets. Author summary Phlebotomus papatasisand flies vectorLeishmania majorparasites, one of the causative agents of cutaneous leishmaniasis (CL). Approximately 0.7-1.2 million cases of CL occur each year. CL produces disfiguring skin lesions for which no vaccine currently exists. Hematophagous arthropods secrete salivary proteins that modulate host inflammation, vasoconstriction, and blood clotting. Salivary proteins from multiple phlebotomine sand fly species have been widely studied and scrutinized to characterize their function in blood feeding as well as their ability to exacerbate or attenuateLeishmaniainfections. Hence their potential role as vaccine or as a component of vaccination strategies. In such regard, we hypothesize that in order to be successful, sand fly salivary protein-based vaccines must consider, in addition to the human immune responses, the genetic variability and the expression profiles of such salivary antigens from geographically distant sand fly populations. The purpose of this study was to analyze the genetic variability of nine of the most abundant secreted salivary proteins identified inP.papatasi, comparing insects collected from distinct ecotopes in Egypt and Jordan.