Schistosoma Tegument Proteins in Vaccine and Diagnosis Development: An Update (original) (raw)
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Experimental parasitology, 2014
Schistosoma mansoni tegument is involved in essential functions for parasite survival and represents a target for screening candidates for vaccine and diagnosis. Our group using reverse vaccinology selected six candidates, previously demonstrated by proteomics studies to be expressed in the parasite tegument, among them was Sm200. In this work we have cloned and expressed a recombinant form of Sm200 C-terminal (1069-1520) region. The efficacy of rSm200 (1069-1520) in the diagnosis of schistosomiasis and in the formulation of a vaccine against S. mansoni was assessed respectively in an ELISA based diagnostic assay and immunization protocols in mice. Significant differences between non-infected and acutely infected or chronically infected animals were observed and no cross-recognition was observed with sera from Ascaris suum or Ancylostoma ceylanicum infected mice. rSm200-ELISA test could also discriminate infected individuals from healthy donors not living in endemic area for schisto...
Frontiers in immunology, 2015
Schistosomiasis is a debilitating disease that represents a major health problem in at least 74 tropical and subtropical countries. Current disease control strategies consist mainly of chemotherapy, which cannot prevent recurrent re-infection of people living in endemic area. In the last decades, many researchers made a remarkable effort in the search for an effective vaccine to provide long-term protection. Parasitic platyhelminthes of Schistosoma genus, which cause the disease, live in the blood vessels of definitive hosts where they are bathed in host blood for many years. Among the most promising molecules as vaccine candidates are the proteins present in the host-parasite interface, so numerous tegument antigens have been assessed and the achieved protection never got even close to 100%. Besides the tegument, the digestive tract is the other major site of host-parasite interface. Since parasites feed on blood, they need to swallow a considerable amount of blood for nutrient acq...
Schistosomes—proteomics studies for potential novel vaccines and drug targets
Drug Discovery Today, 2009
Schistosomiasis is a major health problem and, despite decades of research, only one effective drug, Praziquantel is currently available. Recent expansion of sequence databases on Schistosoma mansoni and S. japonicum has permitted a wealth of novel proteomic studies on several aspects of the organization and development of the parasite in the human host. This unprecedented accumulation of molecular data is allowing a more rational approach to propose drug targets and vaccine candidates, such as proteins located at the parasite surface. Successful preliminary trials of two vaccine candidates that have been detected at the parasite surface by proteomics give grounds for believing that such an approach may provide a fresh start for the field.
Clinical and Experimental Immunology, 2006
Surface proteins of schistosomes are exposed to host tissues and thus present as potential candidate molecules for the development of new intervention strategies. Herein, we have identified a new tegumental protein of Schistosoma mansoni , termed Sm29. In silico analysis revealed a signal peptide, three glycosylation sites and a transmembrane region on Sm29 amino acid sequence. Sm29 transcription in mammalian developmental stages cDNA libraries of S. mansoni was verified by PCR using specific primers for Sm29 nucleotide sequence and it revealed the presence of transcripts in schistosomula and adult worm stages of the parasite. Sm29 (40-169) fragment was produced in Escherichia coli and purified by affinity chromatography to be used in the immunological assays. Confocal microscopy confirmed bioinformatic studies, revealing that Sm29 is a membranebound protein localized on the tegument of S. mansoni adult worm. ELISA was performed using rSm29 protein to investigate the antibody isotype profile to Sm29 in sera of patients living in endemic areas for schistosomiasis. IgG1 and IgG3 subclass antibodies to rSm29 were predominant in sera of individuals naturally resistant to infection and resistant to re-infection whereas low levels of IgM, IgA or IgE were measured. Since, IgG1 and IgG3 are involved in parasite killing and in protective immunity the findings reported here suggest the use of Sm29 as a potential candidate vaccine against schistosomiasis.
Schistosome membrane proteins as vaccines
International Journal for Parasitology, 2007
Schistosomes are parasitic blood flukes that infect approximately 200 million people and are arguably the most important human helminth in terms of mortality. The outermost surface of intra-mammalian stages of the parasite, the tegument, is the key to the parasite's success, but it is also generally viewed as the most susceptible target for vaccines and drugs. Over the past 2 years the proteome of the Schistosoma mansoni tegument has been investigated and these studies revealed surprisingly few proteins that are predicted to be accessible to the host immune response, namely proteins with at least one membrane-spanning domain. However, of this handful of proteins, some are showing great promise as recombinant vaccines against schistosomiasis at a pre-clinical level. In particular, the tetraspanin family of integral membrane proteins appears to be abundantly represented in the tegument, and convergent data using the mouse vaccine model and correlates of protective immunity in naturally exposed people suggests that this family of membrane proteins offer great promise for schistosomiasis vaccines. With the recent advances in schistosome genomics and proteomics, a new suite of potential vaccine antigens are presented and these warrant detailed investigation and appropriate funding over the next few years. Ó
SDS-PAGE Protein Pattern and Antigenicity Cross Reaction of Human Schistosomes
American Journal of Infectious Diseases, 2016
Schistosomiasis is one of the most important neglected tropical diseases. Its control depends on treatment with the available drug praziquantel. No vaccine exists despite the intense search for molecular candidates and adjuvant formulations over the last three decades. The present study aimed to compare the antigenic protein structures of Schistosoma mansoni, S. haematobium, Fasciola. hepatica and Echinococus granulosus hydatid cyst and to find out shared antigens among these species which could be recognized by S. mansoni antibodies. Antigenic protein structures were recognized through the use of Sodium Dodecyl Sulfate-Polyacrylamide Gel Electrophoresis (SDS-PAGE) after Coomassie blue staining. Antigenic differences between the detected polypeptides and positive S. mansoni serum were performed using Western blotting. The SDS-PAGE profiles of the tested parasites revealed many polypeptides ranging from 15-206 kDa. Some of these proteins were shared between all the examined parasites e.g.: 52-47 and 15-25 kDa. Some ranged from 42-38 kDa were shared with both examined schistosomes and hydatid cyst fluid. Bands ranged from 58-55 kDa were common in S. mansoni, S. haematobium and F. hepatica. The protein bands of about 60 kDa crossly reacted with S. mansoni serum and detected in all used antigens. The detected immunoreactive proteins from other helminthes could be used to develop potential vaccine against schistosomiasis.
Acta Tropica, 2011
Tetraspanins (TSPs) are proteins found on the surface of the parasite Schistosoma mansoni that have been regarded as potential protective antigens. However, divergent evolution may occur among the species of S. mansoni and Schistosoma japonicum under different environmental pressure. Thus, it was essential to characterize the S. japonicum TSP family members before selecting potential candidate TSP antigens. In this study, we used bioinformatics and experimental validation to investigate 29 TSP members from S. japonicum, including all known genes, Sj23, TE736, Sj25, and Sj-TSP-2. Five TSP members were found to be variable, and two others (Sj-tsp genes) were alternatively spliced. The phylogenetic analysis showed that schistosome TSPs were highly divergent from those of other phyla. Quantitative RT-PCR revealed that the Sj-tsp genes were differentially transcribed in the developmental stages of cercariae, schistosomula, adult worms, and eggs. Six Sj-tsp genes were significantly up-regulated during the transformation from cercariae to schistosomula. Four Sj-tsp genes, including Sj-tsp-1, Sj-tsp-8, Sj-tsp-14, and Sj-tsp-26 were confirmed as potential protective antigens based on the molecular characterization. RNAi was preformed against the conserved Sj-tsp genes which were highly expressed in schistosomula to explore gene functions. These data will promote the identification of candidate antigens within the TSP family for developing novel vaccines against S. japonicum infections.