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dc.contributor.authorGasan, Thomas A
dc.contributor.authorKuipers, Marije E
dc.contributor.authorRoberts, Grisial H
dc.contributor.authorPadalino, Gilda
dc.contributor.authorForde-Thomas, Josephine E
dc.contributor.authorWilson, Shona
dc.contributor.authorWawrzyniak, Jakub
dc.contributor.authorTukahebwa, Edridah M
dc.contributor.authorHoffmann, Karl F
dc.contributor.authorChalmers, Iain W
dc.date.accessioned2022-01-07T16:50:43Z
dc.date.available2022-01-07T16:50:43Z
dc.date.issued2021-11
dc.identifier.issn1935-2727
dc.identifier.otherPMC8639091
dc.identifier.other34793443
dc.identifier.urihttps://www.repository.cam.ac.uk/handle/1810/332385
dc.descriptionFunder: IBERS, Aberystwyth University PhD studentship
dc.descriptionFunder: Higher Education Funding Council for Wales (HEFCW) - Global Challenges Research Fund
dc.description.abstractExtracellular Vesicles (EVs) are an integral component of cellular/organismal communication and have been found in the excreted/secreted (ES) products of both protozoan and metazoan parasites. Within the blood fluke schistosomes, EVs have been isolated from egg, schistosomula, and adult lifecycle stages. However, the role(s) that EVs have in shaping aspects of parasite biology and/or manipulating host interactions is poorly defined. Herein, we characterise the most abundant EV-enriched protein in Schistosoma mansoni tissue-migrating schistosomula (Schistosoma mansoni Larval Extracellular Vesicle protein 1 (SmLEV1)). Comparative sequence analysis demonstrates that lev1 orthologs are found in all published Schistosoma genomes, yet homologs are not found outside of the Schistosomatidae. Lifecycle expression analyses collectively reveal that smlev1 transcription peaks in cercariae, is male biased in adults, and is processed by alternative splicing in intra-mammalian lifecycle stages. Immunohistochemistry of cercariae using a polyclonal anti-recombinant SmLEV1 antiserum localises this protein to the pre-acetabular gland, with some disperse localisation to the surface of the parasite. S. mansoni-infected Ugandan fishermen exhibit a strong IgG1 response against SmLEV1 (dropping significantly after praziquantel treatment), with 11% of the cohort exhibiting an IgE response and minimal levels of detectable antigen-specific IgG4. Furthermore, mice vaccinated with rSmLEV1 show a slightly reduced parasite burden upon challenge infection and significantly reduced granuloma volumes, compared with control animals. Collectively, these results describe SmLEV1 as a Schistosomatidae-specific, EV-enriched immunogen. Further investigations are now necessary to uncover the full extent of SmLEV1's role in shaping schistosome EV function and definitive host relationships.
dc.languageeng
dc.publisherPublic Library of Science (PLoS)
dc.rightsAttribution 4.0 International
dc.rights.urihttps://creativecommons.org/licenses/by/4.0/
dc.sourceessn: 1935-2735
dc.sourcenlmid: 101291488
dc.subjectAnimals
dc.subjectHumans
dc.subjectMice
dc.subjectSchistosoma mansoni
dc.subjectSchistosomiasis mansoni
dc.subjectPraziquantel
dc.subjectImmunoglobulin E
dc.subjectImmunoglobulin G
dc.subjectHelminth Proteins
dc.subjectVaccines
dc.subjectAntibodies, Helminth
dc.subjectAnthelmintics
dc.subjectCohort Studies
dc.subjectSequence Alignment
dc.subjectAmino Acid Sequence
dc.subjectAdolescent
dc.subjectAdult
dc.subjectMiddle Aged
dc.subjectChild
dc.subjectFemale
dc.subjectMale
dc.subjectYoung Adult
dc.subjectCercaria
dc.subjectExtracellular Vesicles
dc.subjectImmunogenicity, Vaccine
dc.titleSchistosoma mansoni Larval Extracellular Vesicle protein 1 (SmLEV1) is an immunogenic antigen found in EVs released from pre-acetabular glands of invading cercariae.
dc.typeArticle
dc.date.updated2022-01-07T16:50:43Z
prism.issueIdentifier11
prism.publicationNamePLoS Negl Trop Dis
prism.volume15
dc.identifier.doi10.17863/CAM.79831
dcterms.dateAccepted2021-11-06
rioxxterms.versionofrecord10.1371/journal.pntd.0009981
rioxxterms.versionVoR
rioxxterms.licenseref.urihttps://creativecommons.org/licenses/by/4.0/
dc.contributor.orcidGasan, Thomas A [0000-0001-5240-4339]
dc.contributor.orcidKuipers, Marije E [0000-0001-7012-3004]
dc.contributor.orcidRoberts, Grisial H [0000-0002-5811-5033]
dc.contributor.orcidPadalino, Gilda [0000-0001-8580-1293]
dc.contributor.orcidWilson, Shona [0000-0001-5725-4376]
dc.contributor.orcidTukahebwa, Edridah M [0000-0002-0624-2890]
dc.contributor.orcidHoffmann, Karl F [0000-0002-3932-5502]
dc.contributor.orcidChalmers, Iain W [0000-0001-8674-1181]
dc.identifier.eissn1935-2735
pubs.funder-project-idEuropean Commission (242107)
cam.issuedOnline2021-11-18


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Attribution 4.0 International
Except where otherwise noted, this item's licence is described as Attribution 4.0 International