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dc.contributor.authorCecílio, Pedro
dc.contributor.authorPérez-Cabezas, Begoña
dc.contributor.authorFernández, Laura 
dc.contributor.authorMoreno, Javier 
dc.contributor.authorCarrillo, Eugenia 
dc.contributor.authorRequena, José M
dc.contributor.authorFichera, Epifanio
dc.contributor.authorReed, Steven G
dc.contributor.authorColer, Rhea N
dc.contributor.authorKamhawi, Shaden
dc.contributor.authorOliveira, Fabiano
dc.contributor.authorValenzuela, Jesus G
dc.contributor.authorGradoni, Luigi
dc.contributor.authorGlueck, Reinhard
dc.contributor.authorGupta, Gaurav
dc.contributor.authorCordeiro-da-Silva, Anabela
dc.identifier.citationPLoS Negl Trop Dis. 2017 Nov 27;11(11):e0005951.es_ES
dc.description.abstractThe notion that previous infection by Leishmania spp. in endemic areas leads to robust anti-Leishmania immunity, supports vaccination as a potentially effective approach to prevent disease development. Nevertheless, to date there is no vaccine available for human leishmaniasis. We optimized and assessed in vivo the safety and immunogenicity of an innovative vaccine candidate against human visceral leishmaniasis (VL), consisting of Virus-Like Particles (VLP) loaded with three different recombinant proteins (LJL143 from Lutzomyia longipalpis saliva as the vector-derived (VD) component, and KMP11 and LeishF3+, as parasite-derived (PD) antigens) and adjuvanted with GLA-SE, a TLR4 agonist. No apparent adverse reactions were observed during the experimental time-frame, which together with the normal hematological parameters detected seems to point to the safety of the formulation. Furthermore, measurements of antigen-specific cellular and humoral responses, generally higher in immunized versus control groups, confirmed the immunogenicity of the vaccine formulation. Interestingly, the immune responses against the VD protein were reproducibly more robust than those elicited against leishmanial antigens, and were apparently not caused by immunodominance of the VD antigen. Remarkably, priming with the VD protein alone and boosting with the complete vaccine candidate contributed towards an increase of the immune responses to the PD antigens, assessed in the form of increased ex vivo CD4+ and CD8+ T cell proliferation against both the PD antigens and total Leishmania antigen (TLA). Overall, our immunogenicity data indicate that this innovative vaccine formulation represents a promising anti-Leishmania vaccine whose efficacy deserves to be tested in the context of the "natural infection".es_ES
dc.description.sponsorshipThe research leading to these results received funding from the European Community’s Seventh Framework Programme under grant agreement No.603181 [Clinical Studies on a Multivalent Vaccine for Human Visceral Leishmaniasis (MuLeVaClin)] and from the project NORTE-01-0145-FEDER-000012, supported by Norte Portugal Regional Operational Programme (NORTE 2020), under the PORTUGAL 2020 Partnership Agreement, through the European Regional Development Fund (ERDF). Additionally, this study was funded in part by the Division of Intramural Research, National Institute of Allergy and Infectious Diseases (JGV, SK, FO). PC and BPC were supported by fellowships from the European Community’s Seventh Framework Programme under grant agreements No. 603181 (Project MuLeVaClin) and No. 603240-2 (Project NMTryPI), respectively. PC was also supported by Foundation for Science and Technology (FCT), Portugal, through the individual grant SFRH/BD/121252/2016. JM and JMR are supported by a grant from Fondo de Investigaciones Sanitarias (ISCIII-RETICRD16/0027/0008-FEDER). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.es_ES
dc.publisherPublic Library of Sciencees_ES
dc.relation.isversionofPublisher's versiones_ES
dc.subject.meshAdjuvants, Immunologic es_ES
dc.subject.meshAnimals es_ES
dc.subject.meshAntibodies, Protozoan es_ES
dc.subject.meshAntigens, Protozoan es_ES
dc.subject.meshHumans es_ES
dc.subject.meshImmunity, Cellular es_ES
dc.subject.meshImmunity, Humoral es_ES
dc.subject.meshLeishmania donovani es_ES
dc.subject.meshLeishmaniasis Vaccines es_ES
dc.subject.meshLeishmaniasis, Visceral es_ES
dc.subject.meshLymphocyte Activation es_ES
dc.subject.meshMale es_ES
dc.subject.meshMice es_ES
dc.subject.meshMice, Inbred BALB C es_ES
dc.subject.meshPsychodidae es_ES
dc.subject.meshRecombinant Proteins es_ES
dc.subject.meshSaliva es_ES
dc.subject.meshImmunogenicity, Vaccinees_ES
dc.titlePre-clinical antigenicity studies of an innovative multivalent vaccine for human visceral leishmaniasises_ES
dc.rights.licenseAtribución 4.0 Internacional*
dc.contributor.funder7º Programa Marco-Comisión Europea
dc.contributor.funderEuropean Regional Development Fund (ERDF/FEDER)
dc.contributor.funderNational Institutes of Health (United States)
dc.identifier.journalPLoS neglected tropical diseaseses_ES
dc.repisalud.centroISCIII::Centro Nacional de Microbiologíaes_ES

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