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dc.contributor.authorPearson, Mark S
dc.contributor.authorTedla, Bemnet A
dc.contributor.authorBecker, Luke
dc.contributor.authorNakajima, Rie
dc.contributor.authorJasinskas, Al
dc.contributor.authorMduluza, Takafira
dc.contributor.authorMutapi, Francisca
dc.contributor.authorOeuvray, Claude
dc.contributor.authorGreco, Beatrice
dc.contributor.authorSotillo, Javier 
dc.contributor.authorFelgner, Philip L
dc.contributor.authorLoukas, Alex
dc.identifier.citationFront Immunol. 2021 May 25;12:663041.es_ES
dc.description.abstractDespite the enormous morbidity attributed to schistosomiasis, there is still no vaccine to combat the disease for the hundreds of millions of infected people. The anthelmintic drug, praziquantel, is the mainstay treatment option, although its molecular mechanism of action remains poorly defined. Praziquantel treatment damages the outermost surface of the parasite, the tegument, liberating surface antigens from dying worms that invoke a robust immune response which in some subjects results in immunologic resistance to reinfection. Herein we term this phenomenon Drug-Induced Vaccination (DIV). To identify the antigenic targets of DIV antibodies in urogenital schistosomiasis, we constructed a recombinant proteome array consisting of approximately 1,000 proteins informed by various secretome datasets including validated proteomes and bioinformatic predictions. Arrays were screened with sera from human subjects treated with praziquantel and shown 18 months later to be either reinfected (chronically infected subjects, CI) or resistant to reinfection (DIV). IgG responses to numerous antigens were significantly elevated in DIV compared to CI subjects, and indeed IgG responses to some antigens were completely undetectable in CI subjects but robustly recognized by DIV subjects. One antigen in particular, a cystatin cysteine protease inhibitor stood out as a unique target of DIV IgG, so recombinant cystatin was produced, and its vaccine efficacy assessed in a heterologous Schistosoma mansoni mouse challenge model. While there was no significant impact of vaccination with adjuvanted cystatin on adult worm numbers, highly significant reductions in liver egg burdens (45-55%, P<0.0001) and intestinal egg burdens (50-54%, P<0.0003) were achieved in mice vaccinated with cystatin in two independent trials. This study has revealed numerous antigens that are targets of DIV antibodies in urogenital schistosomiasis and offer promise as subunit vaccine targets for a drug-linked vaccination approach to controlling schistosomiasis.es_ES
dc.description.sponsorshipThis study received financial support from Merck KGaA, Darmstadt, Germany, and the Australian Trade and Investment Commission (Australian Tropical Medicine Commercialisation grants program ATMC50322). The funder was not involved in the study design, collection, analysis, interpretation of data, the writing of this article or the decision to submit it for publication. AL was funded by an NHMRC Senior Principal Research Fellowship (APP1117504). FM was funded by the Thrasher Research Fund (12440) and the Wellcome Trust (108061/Z/15/Z). The authors thank Atik Susianto for maintenance of the parasites and laboratory animals. They also gratefully acknowledge the NIAID Schistosomiasis Research Center of the Biomedical Research Institute, Rockville, MD, USA for the provision of S. mansoni-infected B. glabrata snails for this work through NIH-NIAID contract HHSN2722017000141 for distribution through BEI resources.es_ES
dc.publisherFrontiers Media es_ES
dc.subjectProteome microarrayes_ES
dc.subjectUrogenital schistosomiasises_ES
dc.titleImmunomics-Guided Antigen Discovery for Praziquantel-Induced Vaccination in Urogenital Human Schistosomiasises_ES
dc.typejournal articlees_ES
dc.rights.licenseAtribución 4.0 Internacional*
dc.contributor.funderMerck KGaA es_ES
dc.contributor.funderAustralian Trade and Investment Commission es_ES
dc.contributor.funderNational Health and Medical Research Council (Australia) es_ES
dc.contributor.funderThrasher Research Fund es_ES
dc.contributor.funderWellcome Trust es_ES
dc.contributor.funderNIH - National Institute of Allergy and Infectious Diseases (NIAID) (Estados Unidos) es_ES
dc.identifier.journalFrontiers In Immunologyes_ES
dc.repisalud.centroISCIII::Centro Nacional de Microbiologíaes_ES
dc.rights.accessRightsopen accesses_ES

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Atribución 4.0 Internacional
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