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

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 consistin...

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Autores principales:	Laura Fernández, Jose Carlos Solana, Carmen Sánchez, Mª Ángeles Jiménez, Jose M. Requena, Rhea Coler, Steven G. Reed, Jesus G. Valenzuela, Shaden Kamhawi, Fabiano Oliveira, Epifanio Fichera, Reinhard Glueck, Maria Elena Bottazzi, Gaurav Gupta, Pedro Cecilio, Begoña Pérez-Cabezas, Anabela Cordeiro-da-Silva, Luigi Gradoni, Eugenia Carrillo, Javier Moreno
Formato:	article
Lenguaje:	EN
Publicado:	MDPI AG 2021
Materias:	leishmaniasis hamster vaccine virosomes KMP11 LEISH-F3 Biology (General) QH301-705.5
Acceso en línea:	https://doaj.org/article/117c18657fb5436286218190c48f7d64
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spelling	oai:doaj.org-article:117c18657fb5436286218190c48f7d642021-11-25T18:24:37ZProtective 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 Adjuvant10.3390/microorganisms91122532076-2607https://doaj.org/article/117c18657fb5436286218190c48f7d642021-10-01T00:00:00Zhttps://www.mdpi.com/2076-2607/9/11/2253https://doaj.org/toc/2076-2607Visceral 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 <i>Leishmania</i> 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 <i>Leishmania infantum</i>. 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 <i>Leishmania</i> antigens (SLA). Overall, these results indicate that this innovative vaccine formulation confers protection against <i>L. infantum</i> 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.Laura FernándezJose Carlos SolanaCarmen SánchezMª Ángeles JiménezJose M. RequenaRhea ColerSteven G. ReedJesus G. ValenzuelaShaden KamhawiFabiano OliveiraEpifanio FicheraReinhard GlueckMaria Elena BottazziGaurav GuptaPedro CecilioBegoña Pérez-CabezasAnabela Cordeiro-da-SilvaLuigi GradoniEugenia CarrilloJavier MorenoMDPI AGarticleleishmaniasishamstervaccinevirosomesKMP11LEISH-F3Biology (General)QH301-705.5ENMicroorganisms, Vol 9, Iss 2253, p 2253 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	leishmaniasis hamster vaccine virosomes KMP11 LEISH-F3 Biology (General) QH301-705.5
spellingShingle	leishmaniasis hamster vaccine virosomes KMP11 LEISH-F3 Biology (General) QH301-705.5 Laura Fernández Jose Carlos Solana Carmen Sánchez Mª Ángeles Jiménez Jose M. Requena Rhea Coler Steven G. Reed Jesus G. Valenzuela Shaden Kamhawi Fabiano Oliveira Epifanio Fichera Reinhard Glueck Maria Elena Bottazzi Gaurav Gupta Pedro Cecilio Begoña Pérez-Cabezas Anabela Cordeiro-da-Silva Luigi Gradoni Eugenia Carrillo Javier Moreno 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
description	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 <i>Leishmania</i> 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 <i>Leishmania infantum</i>. 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 <i>Leishmania</i> antigens (SLA). Overall, these results indicate that this innovative vaccine formulation confers protection against <i>L. infantum</i> 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.
format	article
author	Laura Fernández Jose Carlos Solana Carmen Sánchez Mª Ángeles Jiménez Jose M. Requena Rhea Coler Steven G. Reed Jesus G. Valenzuela Shaden Kamhawi Fabiano Oliveira Epifanio Fichera Reinhard Glueck Maria Elena Bottazzi Gaurav Gupta Pedro Cecilio Begoña Pérez-Cabezas Anabela Cordeiro-da-Silva Luigi Gradoni Eugenia Carrillo Javier Moreno
author_facet	Laura Fernández Jose Carlos Solana Carmen Sánchez Mª Ángeles Jiménez Jose M. Requena Rhea Coler Steven G. Reed Jesus G. Valenzuela Shaden Kamhawi Fabiano Oliveira Epifanio Fichera Reinhard Glueck Maria Elena Bottazzi Gaurav Gupta Pedro Cecilio Begoña Pérez-Cabezas Anabela Cordeiro-da-Silva Luigi Gradoni Eugenia Carrillo Javier Moreno
author_sort	Laura Fernández
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
title_short	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
title_full	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
title_fullStr	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
title_full_unstemmed	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
title_sort	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
publisher	MDPI AG
publishDate	2021
url	https://doaj.org/article/117c18657fb5436286218190c48f7d64
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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

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