Preliminary analysis of Sm14 in distinct fractions of Schistosoma mansoni adult worm extract

Thaumaturgo, Nilton; Vilar, Mônica Magno; Diogo, Catia Maria; Edelenyi, Ricardo; Tendler, Míriam

doi:10.1590/s0074-02762001000900011

Cited by 7 publications

(4 citation statements)

References 30 publications

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“…We believe these proteins are in vitro artifacts, especially given the lack of in vivo validation and absence of immune recognition. We suggest that FABP probably functions in intraparasite lipid transport in adult F. hepatica despite being found in ES preparations in previous in vitro studies on F. hepatica (6) and Schistosoma mansoni (37). Bile contains high levels of fatty acids that allow the parasite to avoid synthesis and simply take up fatty acids from the host (38).…”

Section: Discussionmentioning

confidence: 79%

Comparative Proteomics of Excretory-Secretory Proteins Released by the Liver Fluke Fasciola hepatica in Sheep Host Bile and during in Vitro Culture ex Host

Morphew

Wright

LaCourse

et al. 2007

Molecular & Cellular Proteomics

139

138

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Section: Discussionmentioning

confidence: 79%

Comparative Proteomics of Excretory-Secretory Proteins Released by the Liver Fluke Fasciola hepatica in Sheep Host Bile and during in Vitro Culture ex Host

Morphew

Wright

LaCourse

et al. 2007

Molecular & Cellular Proteomics

139

138

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“…31,32 Based on the success of RA cercariae vaccination, several candidate antigens were identified based on reactivity of cells and sera from immunized mice. The results from testing these candidate antigens were less promising but provided the premise for two vaccine candidates: recombinant 28-kDa glutathione S-transferase of Schistosoma haematobium (rSh28GST) [33][34][35] and 14-kDa fatty acid-binding protein from Schistosoma mansoni (Sm14), [36][37][38][39][40] which have successfully completed phase III and phase IIa trials, respectively. The development of other candidate antigens has focused primarily on identifying key molecules that play crucial roles in parasite survival, such as membrane biogenesis/renewal, nutrient uptake and immune evasion strategies.…”

Section: What We Have Learnt From Experimental Animal Studiesmentioning

confidence: 99%

<p>Current Understanding of Immunity Against Schistosomiasis: Impact on Vaccine and Drug Development</p>

Molehin

2020

RRTM

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Schistosomiasis is a neglected tropical disease inflicting significant morbidity in humans worldwide. The disease is caused by infections with a parasitic trematode belonging to the genus Schistosoma . Over 250 million people are currently infected globally, with an estimated disability-adjusted life-years of 1.9 million attributed to the disease. Current understanding, based on several immunological studies using experimental and human models of schistosomiasis, reveals that complex immune mechanisms play off each other in the acquisition of immune resistance to infection/reinfection. Nevertheless, the precise characteristics of these responses, the specific antigens against which they are elicited, and how these responses are intricately regulated are still being investigated. What is apparent is that immunity to schistosome infections develops slowly and over a prolonged period of time, augmented by the death of adult worms occurring naturally or by praziquantel therapy. In this review, aspects of immunity to schistosomiasis, host–parasite interactions and their impact on schistosomiasis vaccine development are discussed.

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“…FABPs are expressed in all parasitic life cycle stages. Cytoplasmic FABPs allow schistosomes to acquire fatty acids and cholesterol from the host due to a lack of schistosome oxygen-dependent synthetic pathways essential for membrane formation, protein anchoring, maturation, and egg production (75)(76)(77)(78)(79). Sm FABP shares 91%, 45%, 39% and 49% sequence homology with FABPs of Sj, Echinococcus granulosus, Fasciola hepatica, and Clonorchis sinensis, respectively; phylogenetic proximity may suggest potential for cross-species protection (80)(81)(82)(83).…”

Section: S Mansoni Fatty Acid-binding Protein: Sm14mentioning

confidence: 99%

“…Early murine experiments showed worm reductions ranging from 20-67%, and strong Th1-predominant responses without impacting granulomatous-fibrotic reactions (92)(93)(94)(95)(96)(97)(98)(99)(100). Further rodents immunized with Sm14 with CFA or pRSET-His-rSm14, showed 72% protection and prevention of parasite maturation and hepatic tissue damage by 100% (79,(84)(85)(86)(87)101).…”

Section: S Mansoni Fatty Acid-binding Protein: Sm14mentioning

confidence: 99%

Recent Advances and Methodological Considerations on Vaccine Candidates for Human Schistosomiasis

et al. 2021

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Schistosomiasis remains a neglected tropical disease of major public health concern with high levels of morbidity in various parts of the world. Although considerable efforts in implementing mass drug administration programs utilizing praziquantel have been deployed, schistosomiasis is still not contained. A vaccine may therefore be an essential part of multifaceted prevention control efforts. In the 1990s, a joint United Nations committee promoting parasite vaccines shortlisted promising candidates including for schistosomiasis discussed below. After examining the complexity of immune responses in human hosts infected with schistosomes, we review and discuss the antigen design and preclinical and clinical development of the four leading vaccine candidates: Sm-TSP-2 in Phase 1b/2b, Sm14 in Phase 2a/2b, Sm-p80 in Phase 1 preparation, and Sh28GST in Phase 3. Our assessment of currently leading vaccine candidates revealed some methodological issues that preclude a fair comparison between candidates and the rationale to advance in clinical development. These include (1) variability in animal models - in particular non-human primate studies - and predictive values of each for protection in humans; (2) lack of consensus on the assessment of parasitological and immunological parameters; (3) absence of reliable surrogate markers of protection; (4) lack of well-designed parasitological and immunological natural history studies in the context of mass drug administration with praziquantel. The controlled human infection model - while promising and unique - requires validation against efficacy outcomes in endemic settings. Further research is also needed on the impact of advanced adjuvants targeting specific parts of the innate immune system that may induce potent, protective and durable immune responses with the ultimate goal of achieving meaningful worm reduction.

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Preliminary analysis of Sm14 in distinct fractions of Schistosoma mansoni adult worm extract

Cited by 7 publications

References 30 publications

Comparative Proteomics of Excretory-Secretory Proteins Released by the Liver Fluke Fasciola hepatica in Sheep Host Bile and during in Vitro Culture ex Host

Comparative Proteomics of Excretory-Secretory Proteins Released by the Liver Fluke Fasciola hepatica in Sheep Host Bile and during in Vitro Culture ex Host

<p>Current Understanding of Immunity Against Schistosomiasis: Impact on Vaccine and Drug Development</p>

Recent Advances and Methodological Considerations on Vaccine Candidates for Human Schistosomiasis

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