BackgroundSchistosomiasis continues to be a significant public health problem. This disease affects 200 million people worldwide and almost 800 million people are at risk of acquiring the infection. Although vaccine development against this disease has experienced more failures than successes, encouraging results have recently been obtained using membrane-spanning protein antigens from the tegument of Schistosoma mansoni. Our group recently identified Sm29, another antigen that is present at the adult worm tegument surface. In this study, we investigated murine cellular immune responses to recombinant (r) Sm29 and tested this protein as a vaccine candidate.Methods and FindingsWe first show that Sm29 is located on the surface of adult worms and lung-stage schistosomula through confocal microscopy. Next, immunization of mice with rSm29 engendered 51%, 60% and 50% reduction in adult worm burdens, in intestinal eggs and in liver granuloma counts, respectively (p<0.05). Protective immunity in mice was associated with high titers of specific anti-Sm29 IgG1 and IgG2a and elevated production of IFN-γ, TNF-α and IL-12, a typical Th1 response. Gene expression analysis of worms recovered from rSm29 vaccinated mice relative to worms from control mice revealed a significant (q<0.01) down-regulation of 495 genes and up-regulation of only 22 genes. Among down-regulated genes, many of them encode surface antigens and proteins associated with immune signals, suggesting that under immune attack schistosomes reduce the expression of critical surface proteins.ConclusionThis study demonstrates that Sm29 surface protein is a new vaccine candidate against schistosomiasis and suggests that Sm29 vaccination associated with other protective critical surface antigens is the next logical strategy for improving protection.
The human hookworm Necator americanus infects more than 400 million people worldwide, contributing substantially to the poverty in these regions. Adult stage N. americanus live in the small intestine of the human host where they inject excretory/secretory (ES) products into the mucosa. ES products have been characterized at the proteome level for a number of animal hookworm species, but until now, the difficulty in obtaining sufficient live N. americanus has been an obstacle in characterizing the secretome of this important human pathogen. Herein we describe the ES proteome of N. americanus and utilize this information along with RNA Seq data to conduct the first proteogenomic analysis of a parasitic helminth, significantly improving the available genome and thereby generating a robust description of the parasite secretome. The genome annotation resulted in a revised prediction of 3,425 fewer genes than initially reported, accompanied by a significant increase in the number of exons and introns, total gene length and the percentage of the genome covered by genes. Almost 200 ES proteins were identified by LC-MS/MS with SCP/TAPS proteins, 'hypothetical' proteins and proteases among the most abundant families. These proteins were compared to commonly used model species of human parasitic infections, including Ancylostoma caninum, Nippostrongylus brasiliensis and Heligmosomoides polygyrus. SCP/ TAPS proteins are immunogenic in nematode infections, so we expressed four of those identified in this study in recombinant form and showed that they are all recognized to varying degrees by serum antibodies from hookworm-infected subjects from a disease-endemic area of Brazil. Our findings provide valuable information on important families of proteins a1111111111 a1111111111 a1111111111 a1111111111 a1111111111
The platynosomiasis, a worldwide parasitic disease with importance for domestic cat, has an etiological agent species of trematodes of the genus Platynosomum, whose complete life cycles are not yet known. The real role of lizards in the transmission of this dicrocoeliid parasite (as obligatory intermediate or paratenic host) still needs to be defined. In the present study, oval-shaped encysted metacercariae obtained from terrestrial isopods (Oniscidea sp. and Nagurus nanus) and elongated excysted metacercariae found in biliary ducts and gallbladder of lizards (Hemidactylus mabouia) in Brazil were used for morphological characterization and experimental infection of mice. Adult parasites recovered from bile ducts and liver of mice inoculated orally with metacercariae from both hosts (isopods and lizards) were identified as Platynosomum illiciens (=Platynosomum fastosum), showing that lizards are paratenic (not obligatory) hosts involved in the life cycle of this parasite. Moreover, Subulina octona is reported as the first intermediate host of P. illiciens in South America, and terrestrial isopods are presented here as new natural second intermediate hosts of the parasite. Finally, it is pointed out that high prevalence and intensity of infection of intermediate and paratenic hosts were observed. These findings on the life cycle of P. illiciens are relevant considering that they may indicate possible control measures of platynosomiasis.
Although feline platynosomosis has been commonly reported in several parts of the world, the taxonomy and epidemiological chain related to cat liver flukes remain controversial. In this study, nuclear ribosomal ITS, 28S, and mitochondrial cox1 sequences obtained for Platynosomum illiciens from cat, marmoset, lizard, and snail found naturally infected in Brazil reveal no significant molecular differences between these isolates. Moreover, sequence data confirm that Brazilian P. illiciens from different hosts is conspecific with parasites obtained from cats in Vietnam, supporting wide distribution of the species. The lack of pronounced specificity of P. illiciens to definitive hosts is confirmed here for the first time using molecular approach. The results are discussed in context of the epizootology of platynosomosis.
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