{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,18]],"date-time":"2026-01-18T07:12:50Z","timestamp":1768720370394,"version":"3.49.0"},"reference-count":69,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2021,10,29]],"date-time":"2021-10-29T00:00:00Z","timestamp":1635465600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"European Community's Seventh Framework Programme","award":["603181"],"award-info":[{"award-number":["603181"]}]},{"name":"Red de Investigaci\u00f3n Cooperativa de Enfermedades Tropicales, Subprograma RETICS del Plan Estatal de I+D+I 2013\u20132016, co-funded by ERDF \u201cUna manera de hacer Europa","award":["RD16CIII\/0003\/0002"],"award-info":[{"award-number":["RD16CIII\/0003\/0002"]}]},{"name":"Red de Investigaci\u00f3n Cooperativa de Enfermedades Tropicales, Subprograma RETICS del Plan Estatal de I+D+I 2013\u20132016, co-funded by ERDF \u201cUna manera de hacer Europa","award":["RD16\/0027\/0008"],"award-info":[{"award-number":["RD16\/0027\/0008"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Microorganisms"],"abstract":"<jats:p>Visceral 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.<\/jats:p>","DOI":"10.3390\/microorganisms9112253","type":"journal-article","created":{"date-parts":[[2021,11,1]],"date-time":"2021-11-01T22:22:24Z","timestamp":1635805344000},"page":"2253","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":17,"title":["Protective 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 Adjuvant"],"prefix":"10.3390","volume":"9","author":[{"given":"Laura","family":"Fern\u00e1ndez","sequence":"first","affiliation":[{"name":"WHO Collaborating Centre for Leishmaniasis, Centro Nacional de Microbiolog\u00eda, Instituto de Salud Carlos III, 28220 Madrid, Spain"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0485-6127","authenticated-orcid":false,"given":"Jose Carlos","family":"Solana","sequence":"additional","affiliation":[{"name":"WHO Collaborating Centre for Leishmaniasis, Centro Nacional de Microbiolog\u00eda, Instituto de Salud Carlos III, 28220 Madrid, Spain"}]},{"given":"Carmen","family":"S\u00e1nchez","sequence":"additional","affiliation":[{"name":"WHO Collaborating Centre for Leishmaniasis, Centro Nacional de Microbiolog\u00eda, Instituto de Salud Carlos III, 28220 Madrid, Spain"}]},{"given":"M\u00aa \u00c1ngeles","family":"Jim\u00e9nez","sequence":"additional","affiliation":[{"name":"Facultad de Veterinaria, Departamento de Medicina y Cirug\u00eda Animal, Universidad Complutense de Madrid, 28040 Madrid, Spain"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7550-0198","authenticated-orcid":false,"given":"Jose M.","family":"Requena","sequence":"additional","affiliation":[{"name":"Centro de Biolog\u00eda Molecular Severo Ochoa (CSIC-UAM), Universidad Aut\u00f3noma de Madrid, 28049 Madrid, Spain"}]},{"given":"Rhea","family":"Coler","sequence":"additional","affiliation":[{"name":"Center for Global Infectious Disease Research (CGIDR), Seattle Children\u2019s Research Institute, Seattle, WA 98109, USA"}]},{"given":"Steven G.","family":"Reed","sequence":"additional","affiliation":[{"name":"HDT Bio Corp, Seattle, WA 98102, USA"}]},{"given":"Jesus G.","family":"Valenzuela","sequence":"additional","affiliation":[{"name":"Vector Molecular Biology Section, Laboratory of Malaria and Vector Research, NIAID, NIH, Rockville, MD 20852, USA"}]},{"given":"Shaden","family":"Kamhawi","sequence":"additional","affiliation":[{"name":"Vector Molecular Biology Section, Laboratory of Malaria and Vector Research, NIAID, NIH, Rockville, MD 20852, USA"}]},{"given":"Fabiano","family":"Oliveira","sequence":"additional","affiliation":[{"name":"Vector Molecular Biology Section, Laboratory of Malaria and Vector Research, NIAID, NIH, Rockville, MD 20852, USA"}]},{"given":"Epifanio","family":"Fichera","sequence":"additional","affiliation":[{"name":"Etna Biotech S.R.L, 95121 Catania, Italy"}]},{"given":"Reinhard","family":"Glueck","sequence":"additional","affiliation":[{"name":"Etna Biotech S.R.L, 95121 Catania, Italy"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8429-0476","authenticated-orcid":false,"given":"Maria Elena","family":"Bottazzi","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Texas Children\u2019s Center for Vaccine Development, National School of Tropical Medicine, Baylor College of Medicine, Houston, TX 77030, USA"}]},{"given":"Gaurav","family":"Gupta","sequence":"additional","affiliation":[{"name":"Etna Biotech S.R.L, 95121 Catania, Italy"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5945-5040","authenticated-orcid":false,"given":"Pedro","family":"Cecilio","sequence":"additional","affiliation":[{"name":"Parasite Disease Group, Instituto de Investiga\u00e7\u00e3o e Inova\u00e7\u00e3o em Sa\u00fade (i3S), Universidade do Porto, 4200-135 Porto, Portugal"},{"name":"IBMC-Instituto de Biologia Celular E Molecular, Universidade do Porto, 4150-180 Porto, Portugal"},{"name":"Faculdade de Farm\u00e1cia da, Universidade do Porto, 4099-002 Porto, Portugal"}]},{"given":"Bego\u00f1a","family":"P\u00e9rez-Cabezas","sequence":"additional","affiliation":[{"name":"Parasite Disease Group, Instituto de Investiga\u00e7\u00e3o e Inova\u00e7\u00e3o em Sa\u00fade (i3S), Universidade do Porto, 4200-135 Porto, Portugal"},{"name":"IBMC-Instituto de Biologia Celular E Molecular, Universidade do Porto, 4150-180 Porto, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2392-6087","authenticated-orcid":false,"given":"Anabela","family":"Cordeiro-da-Silva","sequence":"additional","affiliation":[{"name":"Parasite Disease Group, Instituto de Investiga\u00e7\u00e3o e Inova\u00e7\u00e3o em Sa\u00fade (i3S), Universidade do Porto, 4200-135 Porto, Portugal"},{"name":"IBMC-Instituto de Biologia Celular E Molecular, Universidade do Porto, 4150-180 Porto, Portugal"},{"name":"Faculdade de Farm\u00e1cia da, Universidade do Porto, 4099-002 Porto, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0949-6818","authenticated-orcid":false,"given":"Luigi","family":"Gradoni","sequence":"additional","affiliation":[{"name":"Unit of Vector-Borne Diseases, Istituto Superiore di Sanit\u00e0, 00161 Rome, Italy"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7869-7915","authenticated-orcid":false,"given":"Eugenia","family":"Carrillo","sequence":"additional","affiliation":[{"name":"WHO Collaborating Centre for Leishmaniasis, 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