A next-generation proteome array for Schistosoma mansoni

Assis, Rafael Ramiro de; Ludolf, Fernanda; Nakajima, Rie; Jasinskas, Al; Oliveira, Guilherme; Felgner, Philip L.; Gaze, Soraya; Loukas, Alex; LoVerde, Philip T.; Bethony, Jeffrey M.; Correa-Oliveira, Rodrigo; Calzavara-Silva, Carlos Eduardo

doi:10.1016/j.ijpara.2016.04.001

Cited by 25 publications

(19 citation statements)

References 25 publications

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“…Newly available genomic and proteomic data for parasitic nematodes is making high-throughput vaccine antigen discovery, known as “immunomics”, now possible [49–52]. This approach allows for profiling of host immune antibody response to candidate parasitic antigens in a high throughput manner.…”

Section: Where Do We Go From Here?mentioning

confidence: 99%

“…This approach allows for profiling of host immune antibody response to candidate parasitic antigens in a high throughput manner. This assay was employed to identify potential vaccine antigens in the genomes of S. mansoni [52, 53], S. Japonicum [50], Necator americanus [51], and for the first time also in the genome of O. volvulus [35]. Criteria for selecting O. volvulus candidate vaccine proteins on the array have included: 1) abundant expression in L3 and molting L3 or in microfilariae, the targets for prophylactic and therapeutic vaccines, respectively [54], 2) predicted secretion based on the presence of a leader sequence or other motifs, containing 0-3 transmembrane domains and below 50 kDa in size (to increase the probability of efficient expression using the cell-free in vitro transcription and translation systems), and 4) not having a significant human match.…”

Section: Where Do We Go From Here?mentioning

confidence: 99%

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Lessons from the genomes and transcriptomes of filarial nematodes

Grote

Lustigman

Ghedin

2017

Molecular and Biochemical Parasitology

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Human filarial infections are a leading cause of morbidity in the developing world. While a small arsenal of drugs exists to treat these infections, there remains a tremendous need for the development of additional interventions. Recent genome sequences and transcriptome analyses of filarial nematodes have provided novel biological insight and allowed for the prediction of novel drug targets as well as potential vaccine candidates. In this review, we discuss the currently available data, insights gained into the metabolism of these organisms, and how the filaria field can move forward by leveraging these data.

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Section: Where Do We Go From Here?mentioning

confidence: 99%

Section: Where Do We Go From Here?mentioning

confidence: 99%

Lessons from the genomes and transcriptomes of filarial nematodes

Grote

Lustigman

Ghedin

2017

Molecular and Biochemical Parasitology

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“…We used this new valuable resource to determine the kinetics of the mouse humoral response to S. mansoni infections. While other large arrays of parasite proteins have been used for diagnostic and immuno-epidemiological purposes, they have mostly relied on cell-free or bacterial expression systems [41][42][43]. Mammalian expression systems are more suitable for the addition of structurally important posttranslational modifications found on extracellular proteins and thereby preserve conformational epitopes that can be recognised by antibodies.…”

Section: Discussionmentioning

confidence: 99%

A library of cell-surface and secreted proteins fromSchistosoma mansoniidentifies early serological markers of infection

Crosnier

Protasio

Rinaldi

et al. 2019

Preprint

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Schistosomiasis is a major global health problem caused by blood-dwelling parasitic worms and is currently treated by the mass administration of the drug praziquantel. Appropriate drug treatment strategies are informed by diagnostics that establish the prevalence and intensity of infection, which, in regions of low transmission should be highly sensitive. To identify sensitive new serological markers of Schistosoma mansoni infections, we have compiled a recombinant protein library of 115 parasite cell surface and secreted proteins expressed in mammalian cells. The vast majority of them were shown to be immunoreactive and to contain heat-labile conformational epitopes when tested against pooled human sera from endemic regions. After probing the library against a time series of sera samples from experimental infections in mice, we identified several markers of infection, the majority of which belong to the saposin-domain-containing and cathepsin families of proteins. These new markers will be a valuable tool to detect ongoing and previous S. mansoni infections, including in regions of low transmission. We envisage that this new recombinant protein resource will be used in a wide range of cellular and molecular assays to further our understanding of Schistosoma biology.

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“…The disappointing results of clinical trials for several infectious diseases highlight the current limitations of vaccine candidate selection approaches that often fail to exclude at an early stage antigens with poor immunogenicity or low safety profiles in humans [76,77]. One approach for identifying novel vaccine candidates is immunomics [78–82], which allows high-throughput profiling of the host immune antibody responses to genome-wide candidate parasite antigens. Using this approach with putatively immune human sera and sera from infected individuals [56], six new potential vaccine antigens were identified by screening antibody responses (IgG1, IgG3 and IgE) against an O .…”

Section: High-throughput Immunomic Screening Of O Volvulus Vaccine Cmentioning

confidence: 99%