Pre-clinical antigenicity studies of an innovative multivalent vaccine for human visceral leishmaniasis
Autor(a) principal: | |
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Data de Publicação: | 2017 |
Outros Autores: | , , , , , , , , , , , , , , |
Tipo de documento: | Artigo |
Idioma: | eng |
Título da fonte: | Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
Texto Completo: | https://repositorio-aberto.up.pt/handle/10216/118199 |
Resumo: | 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”. |
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Pre-clinical antigenicity studies of an innovative multivalent vaccine for human visceral leishmaniasisThe 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 Science20172017-01-01T00:00:00Zinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleapplication/pdfhttps://repositorio-aberto.up.pt/handle/10216/118199eng1935-272710.1371/journal.pntd.0005951Cecílio, PPérez-Cabezas, BFernández, L.Moreno, JCarrillo, ERequena, JFichera, EReed, SColer, RKamhawi, SOliveira, FValenzuela, JGradoni, LGlueck, RGupta, GCordeiro-da-Silva, Ainfo:eu-repo/semantics/openAccessreponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãoinstacron:RCAAP2023-11-29T13:15:50Zoai:repositorio-aberto.up.pt:10216/118199Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireopendoar:71602024-03-19T23:36:58.794706Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãofalse |
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, P |
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 |
author |
Cecílio, P |
author_facet |
Cecílio, P Pérez-Cabezas, B Fernández, L. Moreno, J Carrillo, E Requena, J Fichera, E Reed, S Coler, R Kamhawi, S Oliveira, F Valenzuela, J Gradoni, L Glueck, R Gupta, G Cordeiro-da-Silva, A |
author_role |
author |
author2 |
Pérez-Cabezas, B Fernández, L. Moreno, J Carrillo, E Requena, J Fichera, E Reed, S Coler, R Kamhawi, S Oliveira, F Valenzuela, J Gradoni, L Glueck, R Gupta, G Cordeiro-da-Silva, A |
author2_role |
author author author author author author author author author author author author author author author |
dc.contributor.author.fl_str_mv |
Cecílio, P Pérez-Cabezas, B Fernández, L. Moreno, J Carrillo, E Requena, J Fichera, E Reed, S Coler, R Kamhawi, S Oliveira, F Valenzuela, J Gradoni, L Glueck, R Gupta, G Cordeiro-da-Silva, A |
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 2017-01-01T00:00:00Z |
dc.type.status.fl_str_mv |
info:eu-repo/semantics/publishedVersion |
dc.type.driver.fl_str_mv |
info:eu-repo/semantics/article |
format |
article |
status_str |
publishedVersion |
dc.identifier.uri.fl_str_mv |
https://repositorio-aberto.up.pt/handle/10216/118199 |
url |
https://repositorio-aberto.up.pt/handle/10216/118199 |
dc.language.iso.fl_str_mv |
eng |
language |
eng |
dc.relation.none.fl_str_mv |
1935-2727 10.1371/journal.pntd.0005951 |
dc.rights.driver.fl_str_mv |
info:eu-repo/semantics/openAccess |
eu_rights_str_mv |
openAccess |
dc.format.none.fl_str_mv |
application/pdf |
dc.publisher.none.fl_str_mv |
Public Library of Science |
publisher.none.fl_str_mv |
Public Library of Science |
dc.source.none.fl_str_mv |
reponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação instacron:RCAAP |
instname_str |
Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação |
instacron_str |
RCAAP |
institution |
RCAAP |
reponame_str |
Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
collection |
Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
repository.name.fl_str_mv |
Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação |
repository.mail.fl_str_mv |
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1799135682616098817 |