A library of cell-surface and secreted proteins from<i>Schistosoma mansoni</i>identifies early serological markers of infection

Crosnier, Cécile; Protasio, Anna V.; Rinaldi, Gabriel; Wilson, Shona; Berriman, Matthew; Gj, Wright

doi:10.1101/593616

Cited by 1 publication

(7 citation statements)

References 59 publications

(80 reference statements)

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“…We have recently described the selection of a panel of S. mansoni cell-surface and secreted proteins identified from proteomics and transcriptional studies, of which 103 could be produced recombinantly in human embryonic kidney (HEK)-293 cells as soluble ectodomains containing a C-terminal rat Cd4d3+4 tag followed by a sequence for enzymatic monobiotinylation and a 6-His tag for purification 28 . The majority of these proteins were immunoreactive when tested against sera from S. mansoni- infected patients living in areas of high endemicity, and contained heat-labile epitopes demonstrating the presence of conformational epitopes.…”

Section: Resultsmentioning

confidence: 99%

“…By using a mammalian expression system, we have sought to improve the tertiary conformation of the recombinant antigens tested, in particular the formation of structurally critical disulphide bonds. Indeed, immunoreactivity experiments on these proteins against patients’ sera from a highly endemic area have shown that the vast majority of them contain heat-labile conformational epitopes 28 , which are indicative of their correct folding.…”

Section: Discussionmentioning

confidence: 99%

“…Also, the differences in adjuvants, routes of delivery, immunisation regimes and heterologous expression systems used to produce the antigens can lead to contradictory results on the protective effect of certain antigens 25– 27 . We have recently described a library of secreted and cell-surface S. mansoni proteins whose selection was based on published proteomics studies and transcriptional data at the schistosomula stage 28 . Importantly, these proteins were expressed in human embryonic kidney (HEK)-293 cells, to increase the chances of forming disulphide bonds that are critical for the correct tertiary folding of extracellular proteins.…”

Section: Introductionmentioning

confidence: 99%

“…Importantly, these proteins were expressed in human embryonic kidney (HEK)-293 cells, to increase the chances of forming disulphide bonds that are critical for the correct tertiary folding of extracellular proteins. Testing against sera from patients living in a high-endemicity area showed that most of them contain heat-labile conformational epitopes 28 .…”

Section: Introductionmentioning

confidence: 99%

“…All molecules were produced in HEK-293 cells to ensure correct folding of the proteins. The production of the same molecules (without a His tag) is described in a previous paper by Crosnier (reference 28 1 ) who demonstrated by ELISA that the epitopes on the majority of molecules were heat labile – i.e. the purified recombinant bound to antibodies in serum from a pool of infected humans but heat-treated recombinants did not.…”

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confidence: 99%

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Systematic screening of 96 Schistosoma mansoni cell-surface and secreted antigens does not identify any strongly protective vaccine candidates in a mouse model of infection

et al. 2019

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Background: Schistosomiasis is a major parasitic disease affecting people living in tropical and sup-tropical areas. Transmission of the parasite has been reported in 78 countries, causing significant morbidity and around 200,000 deaths per year in endemic regions. The disease is currently managed by the mass-administration of praziquantel to populations at risk of infection; however, the reliance on a single drug raises the prospect of parasite resistance to the only treatment widely available. The development of an effective vaccine would be a more powerful method of control, but none currently exists and the identification of new immunogens that can elicit protective immune responses therefore remains a priority. Because of the complex nature of the parasite life cycle, identification of new vaccine candidates has mostly relied on the use of animal models and on a limited set of recombinant proteins. Methods: In this study, we have established an infrastructure for testing a large number of vaccine candidates in mice and used it to screen 96 cell-surface and secreted recombinant proteins from Schistosoma mansoni. This approach, using standardised immunisation and percutaneous infection protocols, allowed us to compare an extensive set of antigens in a systematic manner. Results: Although some vaccine candidates were associated with a statistically significant reduction in the number of eggs in the initial screens, these observations could not be repeated in subsequent challenges and none of the proteins studied were associated with a strongly protective effect against infection. Conclusions: Although no antigens individually induced reproducible and strongly protective effects using our vaccination regime, we have established the experimental infrastructures to facilitate large-scale systematic subunit vaccine testing for schistosomiasis in a murine infection model.

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Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%