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dc.contributor.authorFernandez, Laura 
dc.contributor.authorSolana, Jose Carlos 
dc.contributor.authorSanchez Herrero, Carmen 
dc.contributor.authorJiménez, Mª Ángeles
dc.contributor.authorRequena, Jose M
dc.contributor.authorColer, Rhea
dc.contributor.authorReed, Steven G
dc.contributor.authorValenzuela, Jesus G
dc.contributor.authorKamhawi, Shaden
dc.contributor.authorOliveira, Fabiano
dc.contributor.authorFichera, Epifanio
dc.contributor.authorGlueck, Reinhard
dc.contributor.authorBottazzi, Maria Elena
dc.contributor.authorGupta, Gaurav
dc.contributor.authorCecilio, Pedro
dc.contributor.authorPérez-Cabezas, Begoña
dc.contributor.authorCordeiro-da-Silva, Anabela
dc.contributor.authorGradoni, Luigi
dc.contributor.authorCarrillo, Eugenia 
dc.contributor.authorMoreno, Javier 
dc.date.accessioned2022-05-06T12:17:12Z
dc.date.available2022-05-06T12:17:12Z
dc.date.issued2021-10-29
dc.identifier.citationMicroorganisms 2021 Oct 29;9(11):2253.es_ES
dc.identifier.issn2076-2607es_ES
dc.identifier.urihttp://hdl.handle.net/20.500.12105/14307
dc.description.abstractVisceral leishmaniasis (VL) is the most severe clinical form of leishmaniasis, fatal if untreated. Vaccination is the most cost-effective approach to disease control; however, to date, no vaccines against human VL have been made available. This work examines the efficacy of a novel vaccine consisting of the Leishmania membrane protein KMP11, LEISH-F3+ (a recombinant fusion protein, composed of epitopes of the parasite proteins nucleoside hydrolase, sterol-24-c-methyltransferase, and cysteine protease B), and the sand fly salivary protein LJL143, in two dose ratios. The inclusion of the TLR4 agonist GLA-SE as an adjuvant, and the use of virosomes (VS) as a delivery system, are also examined. In a hamster model of VL, the vaccine elicited antigen-specific immune responses prior to infection with Leishmania infantum. Of note, the responses were greater when higher doses of KMP11 and LEISH-F3+ proteins were administered along with the GLA-SE adjuvant and/or when delivered within VS. Remarkably, hamsters immunized with the complete combination (i.e., all antigens in VS + GLA-SE) showed significantly lower parasite burdens in the spleen compared to those in control animals. This protection was underpinned by a more intense, specific humoral response against the KMP11, LEISH-F3+, and LJL143 antigens in vaccinated animals, but a significantly less intense antibody response to the pool of soluble Leishmania antigens (SLA). Overall, these results indicate that this innovative vaccine formulation confers protection against L. infantum infection, supporting the advancement of the vaccine formulation into process development and manufacturing and the conduction of toxicity studies towards future phase I human clinical trials.es_ES
dc.description.sponsorshipThis research was funded by the European Community’s Seventh Framework Programme, grant number 603181 (Clinical Studies on a Multivalent Vaccine for Human Visceral Leishmaniasis [MuLeVaClin]), and by the RD16CIII/0003/0002 and RD16/0027/0008 Red de Investigación Cooperativa de Enfermedades Tropicales, Subprograma RETICS del Plan Estatal de I+D+I 2013–2016, co-funded by ERDF “Una manera de hacer Europa” funds.es_ES
dc.language.isoenges_ES
dc.publisherMultidisciplinary Digital Publishing Institute (MDPI) es_ES
dc.type.hasVersionVoRes_ES
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/*
dc.subjectGLA-SEes_ES
dc.subjectKMP11es_ES
dc.subjectLEISH-F3es_ES
dc.subjectLJL143es_ES
dc.subjectHamsteres_ES
dc.subjectLeishmaniasises_ES
dc.subjectVaccinees_ES
dc.subjectVirosomeses_ES
dc.titleProtective Efficacy in a Hamster Model of a Multivalent Vaccine for Human Visceral Leishmaniasis (MuLeVaClin) Consisting of the KMP11, LEISH-F3+, and LJL143 Antigens in Virosomes, Plus GLA-SE Adjuvantes_ES
dc.typejournal articlees_ES
dc.rights.licenseAtribución 4.0 Internacional*
dc.identifier.pubmedID34835379es_ES
dc.format.volume9es_ES
dc.format.number11es_ES
dc.format.page2253es_ES
dc.identifier.doi10.3390/microorganisms9112253es_ES
dc.contributor.funderUnión Europea. Comisión Europea. 7 Programa Marco es_ES
dc.contributor.funderPlan Nacional de I+D+i (España) es_ES
dc.contributor.funderUnión Europea. Fondo Europeo de Desarrollo Regional (FEDER/ERDF) es_ES
dc.description.peerreviewedes_ES
dc.relation.publisherversionhttps://doi.org/10.3390/microorganisms9112253es_ES
dc.identifier.journalMicroorganismses_ES
dc.repisalud.centroISCIII::Centro Nacional de Microbiologíaes_ES
dc.repisalud.institucionISCIIIes_ES
dc.relation.projectIDinfo:eu-repo/grantAgreement/EC/FP7/603181/EUes_ES
dc.rights.accessRightsopen accesses_ES
dc.relation.projectFECYTinfo:eu-repo/grantAgreement/MINECO//RD16%2F0027%2F0008/ES/Red de Investigación Colaborativa en Enfermedades Tropicales RICET/ es_ES
dc.relation.projectFECYTinfo:eu-repo/grantAgreement/ES/RD16CIII/0003/0002es_ES


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Atribución 4.0 Internacional
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