Recombinant salivary protein SALO (Salivary Anticomplement of and to protect against cutaneous leishmaniasis caused by vaccine. Introduction Sand flies are vectors of parasites, causal agents of the neglected tropical disease (NTD) leishmaniasis, which is ranked among the most important NTDs in terms of global disease burden [1] and is re-emerging at alarming rates due to the ongoing conflicts in the Middle East and North Africa [2]. induration and redness in the ear was measure at 48 hours. Na?ve mice (control) were injected with PBS. The data represents the mean standard deviation of a representative experiment with 5 mice per group of two impartial experiments (ANOVA and Tukey test).(PDF) pntd.0005374.s003.pdf (284K) GUID:?8597180E-831C-4A7A-996E-95912679E281 Data Availability StatementAll relevant data are within the paper and its Supporting Information files. Abstract Background Immunity to the sand fly salivary protein SALO (Salivary Anticomplement of and contamination and, more recently, a vaccine combination of a genetically modified with SALO conferred strong protection against contamination. Because of the importance of SALO as a potential component of a leishmaniasis vaccine, a plan to produce this recombinant protein for future scale manufacturing as well as knowledge of its structural characteristics are needed to move SALO forward for the clinical path. Methodology/Principal findings Recombinant SALO was expressed as a soluble secreted protein using 17%. SALO is usually ~80% helical, has no appreciable structural similarities to any human protein, and has limited structural similarity in the C-terminus to members of insect odorant binding proteins. SALO has three predicted human CD4+ T cell epitopes on surface exposed helices. Conclusions/Significance The results indicate that SALO as expressed and purified from is suitable for further scale-up, manufacturing, and testing. SALO has a novel structure, is not similar to any human proteins, is immunogenic in rodents, and does not have the anti-complement activity observed in the native salivary protein which are all important attributes to move this vaccine candidate forward to the clinical path. Author summary Immunity to sand fly salivary proteins has been shown to confer protection against leishmaniasis in rodent models. Recombinant salivary protein SALO (Salivary Anticomplement of and to protect against cutaneous leishmaniasis caused by vaccine. Introduction Sand flies are vectors of parasites, causal agents of the neglected tropical disease (NTD) leishmaniasis, which is ranked among the most important NTDs in terms of global disease burden [1] and is re-emerging at alarming rates due to the ongoing conflicts in the Middle East and North Africa [2]. To date, there is no effective or licensed vaccine HTH-01-015 against human leishmaniasis, despite studies demonstrating the cost-effectiveness of developing Kl such biotechnologies for use in resource-poor settings [3, 4]. Sand flies deliver saliva into the skin of the host while probing for a blood meal. The saliva of blood feeding arthropods, including sand flies, has a number of potent bioactive molecules, such as anticoagulants, vasodilators, and inhibitors of platelet aggregation that assist in acquiring blood meals. In the case of sand flies, some of these bioactive components also modify the immunological environment at the host skin site HTH-01-015 of bite, favoring the establishment of infection in the host [5, 6]. Other biological activities of sand fly saliva have been reported and the proteins responsible for these effects have been identified [7], including Lundep, an endonuclease that destroys neutrophil traps [8]; salivary yellow proteins that bind biogenic amines [9]; and recently SALO (Salivary Anti-complement from infection, immunity to sand fly saliva protects against infection [6, 11]. The protection is correlated to the induction of a Th1 cellular immune response. Recently, a number of salivary proteins have emerged as vaccine candidates against cutaneous leishmaniasis, including PpSP15[12] and Linb11 [13] in rodent models, and PdSP15 in non-human primates[14]. For visceral leishmaniasis, the salivary proteins LJM17 and LJL143 were shown to induce a Th1 immune response in dogs [15]. Immunization with DNA plasmid coding HTH-01-015 for the salivary protein SALO (formerly known as LJM19) was shown.