2026-06-14T03:32:36Zhttps://repisalud.isciii.es/rest/oai/requestoai:repisalud.isciii.es:20.500.12105/68902025-05-07T11:47:30Zcom_20.500.12105_2052com_20.500.12105_2051col_20.500.12105_19609
Repisalud
author
Cecílio, Pedro
author
Pérez-Cabezas, Begoña
author
Fernández, Laura
author
Moreno, Javier
author
Carrillo, Eugenia
author
Requena, Jose M
author
Fichera, Epifanio
author
Reed, Steven G
author
Coler, Rhea N
author
Kamhawi, Shaden
author
Oliveira, Fabiano
author
Valenzuela, Jesus G
author
Gradoni, Luigi
author
Glueck, Reinhard
author
Gupta, Gaurav
author
Cordeiro-da-Silva, Anabela
funder
Unión Europea. Comisión Europea. 7 Programa Marco
funder
Unión Europea. Fondo Europeo de Desarrollo Regional (FEDER/ERDF)
funder
National Institutes of Health (Estados Unidos)
2018-12-18T15:14:38Z
2018-12-18T15:14:38Z
2017-11-27
PLoS Negl Trop Dis. 2017 Nov 27;11(11):e0005951.
10.1371/journal.pntd.0005951
1935-2735
1935-2735
PLoS neglected tropical diseases
29176865
http://hdl.handle.net/20.500.12105/6890
The 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".
eng
Pre-clinical antigenicity studies of an innovative multivalent vaccine for human visceral leishmaniasis
research article
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Pre-ClinicalAntigenicityStudiesOf_2017.pdf.txt