Schistosomiasis, caused by trematode blood flukes of the genus Schistosoma, is recognized as the most important human helminth infection in terms of morbidity and mortality Infection follows direct contact with freshwater harboring free-swimming larval (cercaria) forms of the parasite Despite the existence of the highly effective antischistosome drug praziquantel (PZQ), schistosomiasis is spreading into new areas, and although it is the cornerstone of current control programs, PZQ chemotherapy does have limitations In particular, mass treatment does not prevent reinfection Furthermore, there is increasing concern about the development of parasite resistance to PZQ Consequently, vaccine strategies represent an essential component for the future control of schistosomiasis as an adjunct to chemotherapy An improved understanding of the immune response to schistosome infection, both in animal models and in humans, suggests that development of a vaccine may be possible This review considers aspects of antischistosome protective immunity that are important in the context of vaccine development The current status in the development of vaccines against the African (Schistosoma mansoni and S haematobium) and Asian (S japonicum) schistosomes is then discussed, as are new approaches that may improve the efficacy of available vaccines and aid in the identification of new targets for immune attack

https://cmr.asm.org/content/cmr/21/1/225.full.pdf

Current Status of Vaccines for Schistosomiasis

Excretory/Secretory Proteome of the Adult Developmental Stage of Human Blood Fluke, Schistosoma japonicum

Parasitic helminths of the genus Schistosoma mate, achieve sexual maturity and produce eggs in the bloodstream of their definitive hosts, and the most important pathological consequences of the infection are associated with this process. We have used cDNA microarray technology to initiate genome-wide gene-expression studies of sex and sexual development in mature Schistosoma mansoni parasites. An S. mansoni-specific cDNA microarray was fabricated using 576 expressed sequence tags selected from three cDNA libraries and originating from two different parasite developmental stages. Five independent cDNA microarray hybridizations were analyzed using stringent filtering criteria and careful quality control, leading to the identification of 12 new female-associated and 4 new male-associated gene transcripts in the mature adult schistosome. Statistical analysis of variation demonstrated high levels of agreement within a cDNA microarray (correlation coefficient 0.91; median coefficient of variation 11.1%) and between cDNA microarrays (correlation coefficient 0.90; median coefficient of variation 14.4%). RT-PCR analysis confirmed the cDNA microarray results, thereby supporting the reliability of the system. Our study expands the list of S. mansoni gender-associated gene transcripts from all previous studies by a factor of two. Among the new associations identified, a tyrosinase ortholog was preferentially expressed in the adult female, and a dynein light-chain ortholog was highly induced in the adult male. cDNA microarrays offer the potential for exponential leaps in the understanding of parasite biology and this study shows how molecules involved in sexual biology can be rapidly identified.

/pdf/identification-of-schistosoma-mansoni-gender-associated-gene-512bgmwwhe.pdf

Identification of Schistosoma mansoni gender-associated gene transcripts by cDNA microarray profiling.

Background Schistosomiasis is a major parasitic disease affecting >200 million people in the developing world, and 400 million people are at risk for infection. This study aimed to identify and compare proteins recognized by serum samples from schistosome-exposed individuals before and after curative praziquantel treatment. Methods Proteins recognized by pooled serum samples from Schistosoma haematobium-exposed Zimbabweans were determined by 2-dimensional Western blotting and identified by mass spectrometry. Results Serum samples recognized 71 spots, which resolved to 26 different characterized proteins. Eleven of these proteins have not previously been shown to be immunogenic in natural human infection or in experimental models of schistosomiasis, making them novel antigens in the parasite. Pretreatment serum samples recognized 59 spots, which resolved to 21 different identified proteins. Posttreatment serum samples recognized an additional 12 spots, which resolved to 8 different identified proteins. Of these 8 proteins, 3 had putative isoforms recognized before treatment, and 5 (calreticulin, tropomyosin 1, tropomyosin 2, paramyosin, and triose phosphate isomerase) did not. Conclusions This study is the most comprehensive characterization of S. haematobium antigens to date and describes novel antigens in all schistosome species. Posttreatment results are consistent with praziquantel treatment inducing quantitative and qualitative changes in schistosome-specific antibody responses.

Praziquantel Treatment of Individuals Exposed to Schistosoma haematobium Enhances Serological Recognition of Defined Parasite Antigens

Background: This study compared patterns of recognition of defined Schistosoma haematobium adult worm antigens by serum antibodies from schistosome-exposed Zimbabweans aged 5–18 years. 
Methods: The population was stratified by age and infection intensity into 9 groups within which serum specimens were pooled and used to screen for protein recognition by 2-dimensional Western blotting. Recognized proteins were identified by electrospray ionizing tandem mass spectrometry. 
Results: A total of 71 antigens were recognized by ≥1 of the serum pools. The recognition varied distinctly with host age and infection intensity, with some isoform-specific responses. The repertoire of antigens recognized increased with age, peaking in the oldest participants whose had no or mild-to-moderate infection intensity. The intensity of antigen recognition also increased with age, peaking in the oldest participants with the heaviest infection intensity. 

Conclusions: The recognition of specific schistosome antigens, both in terms of the diversity of antigens recognized and the intensity of antigen recognition, increased with duration of exposure to infection, supporting the hypothesis that the slow development of schistosome-acquired immunity is due to the slow accumulation of responsiveness to relevant parasite antigens.

Age-Related and Infection Intensity-Related Shifts in Antibody Recognition of Defined Protein Antigens in a Schistosome-Exposed Population

Sm14 is a 14-kDa vaccine candidate antigen from Schistosoma mansoni that seems to be involved in cytoplasmic trafficking of fatty acids. Although schistosomes have a high requirement for lipids, they are not able to synthesize fatty acids and sterols de novo. Thus, they must acquire host lipids. In order to determine whether Sm14 is present in different stages of the life cycle of the parasite, we performed RT-PCR. Sm14 mRNA was identified in all stages of the life cycle studied, mainly schistosomulum, adult worm and egg. Additionally, we used a rabbit anti-Sm14 polyclonal antibody in an indirect immunofluorescence assay to localize Sm14 in adult worm sections. The basal lamella of the tegument and the gut epithelium were strongly labeled. These tissues have a high flow of and demand for lipids, a finding that supports the putative role of Sm14 as an intracellular transporter of fatty acids from host cells.

/pdf/sm14-gene-expression-in-different-stages-of-the-schistosoma-54e12ftocs.pdf

S Riengrojpitak

Papers

Sm14 gene expression in different stages of the Schistosoma mansoni life cycle and immunolocalization of the Sm14 protein within the adult worm