Schistosoma mansoni Venom Allergen Like Proteins Present Differential Allergic Responses in a Murine Model of Airway Inflammation

Abstract

BackgroundThe Schistosoma mansoni Venom-Allergen-Like proteins (SmVALs) are members of the SCP/TAPS (Sperm-coating protein/Tpx-1/Ag5/PR-1/Sc7) protein superfamily, which may be important in the host-pathogen interaction. Some of these molecules were suggested by us and others as potential immunomodulators and vaccine candidates, due to their functional classification, expression profile and predicted localization. From a vaccine perspective, one of the concerns is the potential allergic effect of these molecules.Methodology/Principal FindingsHerein, we characterized the putative secreted proteins SmVAL4 and SmVAL26 and explored the mouse model of airway inflammation to investigate their potential allergenic properties. The respective recombinant proteins were obtained in the Pichia pastoris system and the purified proteins used to produce specific antibodies. SmVAL4 protein was revealed to be present only in the cercarial stage, increasing from 0–6 h in the secretions of newly transformed schistosomulum. SmVAL26 was identified only in the egg stage, mainly in the hatched eggs' fluid and also in the secretions of cultured eggs. Concerning the investigation of the allergic properties of these proteins in the mouse model of airway inflammation, SmVAL4 induced a significant increase in total cells in the bronchoalveolar lavage fluid, mostly due to an increase in eosinophils and macrophages, which correlated with increases in IgG1, IgE and IL-5, characterizing a typical allergic airway inflammation response. High titers of anaphylactic IgG1 were revealed by the Passive Cutaneous Anaphylactic (PCA) hypersensitivity assay. Additionally, in a more conventional protocol of immunization for vaccine trials, rSmVAL4 still induced high levels of IgG1 and IgE.ConclusionsOur results suggest that members of the SmVAL family do present allergic properties; however, this varies significantly and therefore should be considered in the design of a schistosomiasis vaccine. Additionally, the murine model of airway inflammation proved to be useful in the investigation of allergic properties of potential vaccine candidates.

On the Three-Finger Protein Domain Fold and CD59-Like Proteins in Schistosoma mansoni

“…This sample was analyzed by SDS-PAGE and stained with Schiff's reagent (Sigma) for detection of glycoproteins as per the manufacturer's recommendations. Bovine Serum Albumin (BSA) (Bio-Rad) (non-glycosylated protein) and rSmVAL4 (glycosylated protein) were used as controls for the specificity of the reaction [45]. The rSmCD59.1 and rSmCD59.2 proteins expressed in P. pastoris were glycosylated (products between 14.4 kDa and 20.1 kDa), based on their staining with Schiff's reagent and increased size in SDS-PAGE (as can be observed by the protein band shift in comparison to the rSmCD59.2 expressed in E. coli (Figure S1).…”

Venom allergen 5is Associated With Deltamethrin Resistance inCulex pipiens pallens(Diptera: Culicidae)

“…Some of the venom allergen-like proteins in Schistosoma mansoni Sambon are suggested to be immune modulators and vaccine candidates (Chalmers et al 2008, Farias et al 2012. The venom allergen 5 gene is one of the major allergens identified in many insect venoms (King and Spangfort 2000) and is often associated with allergic responses in humans (Muller et al 2009).…”

Comparative Analysis of Transcriptional Profiles of Adult Schistosoma japonicum from Different Laboratory Animals and the Natural Host, Water Buffalo

“…SmVALs can be divided into two groups and exhibit various gene expression patterns throughout the entire life-cycle, including genes exclusively expressed in stages involved in intermediate host invasion or definitive host invasion and ubiquitously expressed genes [32]. Because of their potential functional classification, expression patterns and localization, SmVALs have been proposed as potential drug targets and vaccine candidates, and some members have been well characterized recently [66][67][68]. For instance, Farias et al have demonstrated that SmVAL4 and SmVAL26 stimulate differential allergic responses in a murine model of airway inflammation [66]; and in a recent study, egg-derived SmVAL9 was found to carry an N-linked glycan containing a schistosome-specific difucosyl element and function as an immunogenic target during chronic murine schistosomiasis [68].…”

“…Because of their potential functional classification, expression patterns and localization, SmVALs have been proposed as potential drug targets and vaccine candidates, and some members have been well characterized recently [66][67][68]. For instance, Farias et al have demonstrated that SmVAL4 and SmVAL26 stimulate differential allergic responses in a murine model of airway inflammation [66]; and in a recent study, egg-derived SmVAL9 was found to carry an N-linked glycan containing a schistosome-specific difucosyl element and function as an immunogenic target during chronic murine schistosomiasis [68]. In our study, 20 non-redundant S. japonicum venom-allergen-like protein (SjVAL) genes were identified in the genome.…”