Pre-clinical antigenicity studies of an innovative multivalent vaccine for human visceral leishmaniasis

Cecílio, Pedro; Pérez-Cabezas, Begoña; Fernández, Laura; Moreno, Javier; Carrillo, Eugenia; Requena, Jose M; Fichera, Epifanio; Reed, Steven G; Coler, Rhea N; Kamhawi, Shaden; Oliveira, Fabiano; Valenzuela, Jesus G; Gradoni, Luigi; Glueck, Reinhard; Gupta, Gaurav; Cordeiro-da-Silva, Anabela

Pre-clinical antigenicity studies of an innovative multivalent vaccine for human visceral leishmaniasis

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 asse...

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Autores:	Cecílio, Pedro, Pérez-Cabezas, Begoña, Fernández, Laura, Moreno, Javier, Carrillo, Eugenia, Requena, Jose M, Fichera, Epifanio, Reed, Steven G, Coler, Rhea N, Kamhawi, Shaden, Oliveira, Fabiano, Valenzuela, Jesus G, Gradoni, Luigi, Glueck, Reinhard, Gupta, Gaurav, Cordeiro-da-Silva, Anabela
Tipo de recurso:	artículo
Fecha de publicación:	2017
País:	España
Institución:	Instituto de Salud Carlos III (ISCIII)
Repositorio:	Repisalud
Idioma:	inglés
OAI Identifier:	oai:repisalud.isciii.es:20.500.12105/6890
Acceso en línea:	http://hdl.handle.net/20.500.12105/6890
Access Level:	acceso abierto
Palabra clave:	Adjuvants, Immunologic Animals Antibodies, Protozoan Antigens, Protozoan Humans Immunity, Cellular Immunity, Humoral Leishmania donovani Leishmaniasis Vaccines Leishmaniasis, Visceral Lymphocyte Activation Male Mice Mice, Inbred BALB C Psychodidae Recombinant Proteins Saliva Immunogenicity, Vaccine

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spelling	Pre-clinical antigenicity studies of an innovative multivalent vaccine for human visceral leishmaniasisCecílio, PedroPérez-Cabezas, BegoñaFernández, LauraMoreno, JavierCarrillo, EugeniaRequena, Jose MFichera, EpifanioReed, Steven GColer, Rhea NKamhawi, ShadenOliveira, FabianoValenzuela, Jesus GGradoni, LuigiGlueck, ReinhardGupta, GauravCordeiro-da-Silva, AnabelaAdjuvants, ImmunologicAnimalsAntibodies, ProtozoanAntigens, ProtozoanHumansImmunity, CellularImmunity, HumoralLeishmania donovaniLeishmaniasis VaccinesLeishmaniasis, VisceralLymphocyte ActivationMaleMiceMice, Inbred BALB CPsychodidaeRecombinant ProteinsSalivaImmunogenicity, VaccineThe 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".Public Library of Science (PLOS)Unión Europea. Comisión Europea. 7 Programa MarcoUnión Europea. Fondo Europeo de Desarrollo Regional (FEDER/ERDF)National Institutes of Health (Estados Unidos)20182018-12-1820172017-11-2720172017-11-27research articlehttp://purl.org/coar/resource_type/c_2df8fbb1VoRhttp://purl.org/coar/version/c_970fb48d4fbd8a85info:eu-repo/semantics/articleapplication/pdfhttp://hdl.handle.net/20.500.12105/6890reponame:Repisaludinstname:Instituto de Salud Carlos III (ISCIII)InglésengEuropean Commission http://dx.doi.org/10.13039/501100000780 Seventh Framework Programme 603181European Commission http://dx.doi.org/10.13039/501100000780 Seventh Framework Programme 603240open accesshttp://purl.org/coar/access_right/c_abf2Atribución 4.0 Internacionalhttp://creativecommons.org/licenses/by/4.0/info:eu-repo/semantics/openAccessoai:repisalud.isciii.es:20.500.12105/68902026-06-12T12:43:37Z
dc.title.none.fl_str_mv	Pre-clinical antigenicity studies of an innovative multivalent vaccine for human visceral leishmaniasis
title	Pre-clinical antigenicity studies of an innovative multivalent vaccine for human visceral leishmaniasis
spellingShingle	Pre-clinical antigenicity studies of an innovative multivalent vaccine for human visceral leishmaniasis Cecílio, Pedro Adjuvants, Immunologic Animals Antibodies, Protozoan Antigens, Protozoan Humans Immunity, Cellular Immunity, Humoral Leishmania donovani Leishmaniasis Vaccines Leishmaniasis, Visceral Lymphocyte Activation Male Mice Mice, Inbred BALB C Psychodidae Recombinant Proteins Saliva Immunogenicity, Vaccine
title_short	Pre-clinical antigenicity studies of an innovative multivalent vaccine for human visceral leishmaniasis
title_full	Pre-clinical antigenicity studies of an innovative multivalent vaccine for human visceral leishmaniasis
title_fullStr	Pre-clinical antigenicity studies of an innovative multivalent vaccine for human visceral leishmaniasis
title_full_unstemmed	Pre-clinical antigenicity studies of an innovative multivalent vaccine for human visceral leishmaniasis
title_sort	Pre-clinical antigenicity studies of an innovative multivalent vaccine for human visceral leishmaniasis
dc.creator.none.fl_str_mv	Cecílio, Pedro Pérez-Cabezas, Begoña Fernández, Laura Moreno, Javier Carrillo, Eugenia Requena, Jose M Fichera, Epifanio Reed, Steven G Coler, Rhea N Kamhawi, Shaden Oliveira, Fabiano Valenzuela, Jesus G Gradoni, Luigi Glueck, Reinhard Gupta, Gaurav Cordeiro-da-Silva, Anabela
author	Cecílio, Pedro
author_facet	Cecílio, Pedro Pérez-Cabezas, Begoña Fernández, Laura Moreno, Javier Carrillo, Eugenia Requena, Jose M Fichera, Epifanio Reed, Steven G Coler, Rhea N Kamhawi, Shaden Oliveira, Fabiano Valenzuela, Jesus G Gradoni, Luigi Glueck, Reinhard Gupta, Gaurav Cordeiro-da-Silva, Anabela
author_role	author
author2	Pérez-Cabezas, Begoña Fernández, Laura Moreno, Javier Carrillo, Eugenia Requena, Jose M Fichera, Epifanio Reed, Steven G Coler, Rhea N Kamhawi, Shaden Oliveira, Fabiano Valenzuela, Jesus G Gradoni, Luigi Glueck, Reinhard Gupta, Gaurav Cordeiro-da-Silva, Anabela
author2_role	author author author author author author author author author author author author author author author
dc.contributor.none.fl_str_mv	Unión Europea. Comisión Europea. 7 Programa Marco Unión Europea. Fondo Europeo de Desarrollo Regional (FEDER/ERDF) National Institutes of Health (Estados Unidos)
dc.subject.none.fl_str_mv	Adjuvants, Immunologic Animals Antibodies, Protozoan Antigens, Protozoan Humans Immunity, Cellular Immunity, Humoral Leishmania donovani Leishmaniasis Vaccines Leishmaniasis, Visceral Lymphocyte Activation Male Mice Mice, Inbred BALB C Psychodidae Recombinant Proteins Saliva Immunogenicity, Vaccine
topic	Adjuvants, Immunologic Animals Antibodies, Protozoan Antigens, Protozoan Humans Immunity, Cellular Immunity, Humoral Leishmania donovani Leishmaniasis Vaccines Leishmaniasis, Visceral Lymphocyte Activation Male Mice Mice, Inbred BALB C Psychodidae Recombinant Proteins Saliva Immunogenicity, Vaccine
description	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".
publishDate	2017
dc.date.none.fl_str_mv	2017 2017-11-27 2017 2017-11-27 2018 2018-12-18
dc.type.none.fl_str_mv	research article http://purl.org/coar/resource_type/c_2df8fbb1 VoR http://purl.org/coar/version/c_970fb48d4fbd8a85
dc.type.openaire.fl_str_mv	info:eu-repo/semantics/article
format	article
dc.identifier.none.fl_str_mv	http://hdl.handle.net/20.500.12105/6890
url	http://hdl.handle.net/20.500.12105/6890
dc.language.none.fl_str_mv	Inglés eng
language_invalid_str_mv	Inglés
language	eng
dc.relation.none.fl_str_mv	European Commission http://dx.doi.org/10.13039/501100000780 Seventh Framework Programme 603181 European Commission http://dx.doi.org/10.13039/501100000780 Seventh Framework Programme 603240
dc.rights.none.fl_str_mv	open access http://purl.org/coar/access_right/c_abf2 Atribución 4.0 Internacional http://creativecommons.org/licenses/by/4.0/
dc.rights.openaire.fl_str_mv	info:eu-repo/semantics/openAccess
rights_invalid_str_mv	open access http://purl.org/coar/access_right/c_abf2 Atribución 4.0 Internacional http://creativecommons.org/licenses/by/4.0/
eu_rights_str_mv	openAccess
dc.format.none.fl_str_mv	application/pdf
dc.publisher.none.fl_str_mv	Public Library of Science (PLOS)
publisher.none.fl_str_mv	Public Library of Science (PLOS)
dc.source.none.fl_str_mv	reponame:Repisalud instname:Instituto de Salud Carlos III (ISCIII)
instname_str	Instituto de Salud Carlos III (ISCIII)
reponame_str	Repisalud
collection	Repisalud
repository.name.fl_str_mv
repository.mail.fl_str_mv
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score	15,812455

Pre-clinical antigenicity studies of an innovative multivalent vaccine for human visceral leishmaniasis

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