Potencialização do efeito protetor e da memória imunológica pela utilização do adjuvante CAF01 associado a antígenos totais de Leishmania amazonensis (LaAg) pela via intranasal contra a Leishmaniose visceral murina
Autor(a) principal: | |
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Data de Publicação: | 2014 |
Tipo de documento: | Dissertação |
Idioma: | por |
Título da fonte: | Repositório Institucional da Universidade Federal do Espírito Santo (riUfes) |
Texto Completo: | http://repositorio.ufes.br/handle/10/1595 |
Resumo: | The dimethyldioctadecylammonium (DDA) is a quaternary ammonium compound formed by a synthetic amphiphilic lipid comprising a hydrophilic positively charged dimethylammonium head–group attached to two hydrophobic 18-carbon alkyl chains (tail), that has previously been reported for eliciting cell-mediated and humoral responses against pathogens like Mycobacterium tuberculosis and Chlamydia trachomatis. In the present study, we investigated the ability of CAF adjuvant associated with surface antigens of Leishmania amazonensis (LaAg) to induce immunogenic and protective responses in challenge against L. chagasi. So, BALB/c mice were vaccinated by intranasal route with 2 doses of LaAg (25 mg) or LaAg associated with CAF (150 mg) intercalated by 15 days. The measurement of transaminases and creatinine in the animals sera demonstrated the biocompatibility and safety of the LaAg/CAF combination. Besides, IFN-γ and NO produced by splenocytes after LaAg in vitro recall was significantly increased, beyond significantly lymphoproliferative responses and increase of memory cells (TCD4+ CD44+ CD62L+) percentage. Increased IgG and specific subclasses (IgG1 and IgG2a) in sera levels were also observed in mice vaccinated with LaAg associated with CAF when compared to controls. Similarly, animals vaccinated with this formulation and challenged with L. chagasi 15 days after the booster with L. chagasi showed a significant decrease in parasite load in the spleen and liver, associated with increased production of IFN-γ and increased lymphoproliferative responses. Together, our results demonstrate for the first time the feasibility of intranasal vaccine with LaAg/CAF as a effective mechanism for the vaccination against visceral leishmaniasis. |
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Gomes, Daniel Cláudio de OliveiraLeal, Janine MirandaRodrigues, Rodrigo RibeiroSilva, Eduardo de Almeida Marques da2015-11-16T17:32:12Z2014-07-112014-07-11The dimethyldioctadecylammonium (DDA) is a quaternary ammonium compound formed by a synthetic amphiphilic lipid comprising a hydrophilic positively charged dimethylammonium head–group attached to two hydrophobic 18-carbon alkyl chains (tail), that has previously been reported for eliciting cell-mediated and humoral responses against pathogens like Mycobacterium tuberculosis and Chlamydia trachomatis. In the present study, we investigated the ability of CAF adjuvant associated with surface antigens of Leishmania amazonensis (LaAg) to induce immunogenic and protective responses in challenge against L. chagasi. So, BALB/c mice were vaccinated by intranasal route with 2 doses of LaAg (25 mg) or LaAg associated with CAF (150 mg) intercalated by 15 days. The measurement of transaminases and creatinine in the animals sera demonstrated the biocompatibility and safety of the LaAg/CAF combination. Besides, IFN-γ and NO produced by splenocytes after LaAg in vitro recall was significantly increased, beyond significantly lymphoproliferative responses and increase of memory cells (TCD4+ CD44+ CD62L+) percentage. Increased IgG and specific subclasses (IgG1 and IgG2a) in sera levels were also observed in mice vaccinated with LaAg associated with CAF when compared to controls. Similarly, animals vaccinated with this formulation and challenged with L. chagasi 15 days after the booster with L. chagasi showed a significant decrease in parasite load in the spleen and liver, associated with increased production of IFN-γ and increased lymphoproliferative responses. Together, our results demonstrate for the first time the feasibility of intranasal vaccine with LaAg/CAF as a effective mechanism for the vaccination against visceral leishmaniasis.O dimetil dioctadecil amônio (DDA) é um composto quaternário de amônio, formado por um lípido anfifílico sintético ligado a duas cadeias hidrofóbicas de alquilo de 18 carbonos, que apresenta efeito adjuvante, promovendo respostas imunes humoral e celular contra diversos agentes patogênicos, incluindo Mycobacterium tuberculosis e Chlamydia trachomatis. No presente trabalho, nós investigamos a capacidade do adjuvante CAF associado a antígenos totais de Leishmania amazonenses (LaAg) em induzir respostas imunogênicas e protetoras em infecção por L. chagasi. Assim, camundongos BALB/c foram imunizados por via intranasal com 25 mg de LaAg livre ou associado a 150 mg de CAF em 2 doses intervaladas por 15 dias. A dosagem de transaminases e creatinina no soro dos animais demonstraram a biocompatibilidade e segurança da associação LaAg/CAF. Além disso, observamos significantes produções de IFN-g e NO por esplenócitos estimulados com antígenos do parasito, além de significantes respostas linfoproliferativas e maior percentagem de células de memória (TCD4+ CD44+ CD62L+). Níveis aumentados de IgG total e das subclasses específicas (IgG1 e IgG2a) também foram observadas no grupo vacinado com LaAg associado ao CAF, quando comparados com os controles. De forma semelhante, camundongos vacinados com a formulação e desafiados 15 dias após o reforço com L. chagasi, apresentaram uma significante diminuição da carga parasitária no baço e no fígado, associada a uma maior produção de IFN-g e respostas linfoproliferativas significantemente aumentadas. Juntos, nossos dados demonstraram pela primeira vez viabilidade da vacinação intranasal com LaAg associado ao CAF, como um efetivo mecanismo para a vacinação contra a leishmaniose visceral.FAPESTexthttp://repositorio.ufes.br/handle/10/1595porUniversidade Federal do Espírito SantoMestrado em Doenças InfecciosasPrograma de Pós-Graduação em Doenças InfecciosasUFESBRCentro de Ciências da SaúdeMemória imunológicaAdministração intranasalLeishmania chagasiImunização intranasalResposta imuneLeishmaniose visceralMemória - ImunologiaDoenças Infecciosas e Parasitárias61Potencialização do efeito protetor e da memória imunológica pela utilização do adjuvante CAF01 associado a antígenos totais de Leishmania amazonensis (LaAg) pela via intranasal contra a Leishmaniose visceral murinainfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/masterThesisinfo:eu-repo/semantics/openAccessreponame:Repositório Institucional da Universidade Federal do Espírito Santo (riUfes)instname:Universidade Federal do Espírito Santo (UFES)instacron:UFESFAPESORIGINALPotencializacao do efeito protetor e da memoria imunologica pela utilizacao de adjuvante caf01 associado a antigenos totais.pdfPotencializacao do efeito protetor e da memoria imunologica pela utilizacao de adjuvante caf01 associado a antigenos totais.pdfTexto completoapplication/pdf1750590http://repositorio.ufes.br/bitstreams/7d4d75e3-64a7-4eae-8eea-535ab203c7a8/download739a10c2c066ca83f7115a9feedaa81fMD51CC-LICENSElicense_urllicense_urltext/plain; charset=utf-849http://repositorio.ufes.br/bitstreams/89a7885f-b544-4fda-a2af-885a8727cca6/download4afdbb8c545fd630ea7db775da747b2fMD52license_textlicense_texttext/html; charset=utf-821468http://repositorio.ufes.br/bitstreams/93158485-6374-4df7-a1e6-df8a67c64393/downloadae2fe251842ade1134c5d9bb99b6eefeMD53license_rdflicense_rdfapplication/rdf+xml; charset=utf-823148http://repositorio.ufes.br/bitstreams/69236ae5-8d96-412f-ade2-6b4218ec0754/download9da0b6dfac957114c6a7714714b86306MD54LICENSElicense.txtlicense.txttext/plain; charset=utf-81748http://repositorio.ufes.br/bitstreams/0e2ef3c2-0445-4027-b3b6-abd5783572fd/download8a4605be74aa9ea9d79846c1fba20a33MD5510/15952024-06-27 11:08:29.038oai:repositorio.ufes.br:10/1595http://repositorio.ufes.brRepositório InstitucionalPUBhttp://repositorio.ufes.br/oai/requestopendoar:21082024-06-27T11:08:29Repositório Institucional da Universidade Federal do Espírito Santo (riUfes) - Universidade Federal do Espírito Santo (UFES)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 |
dc.title.none.fl_str_mv |
Potencialização do efeito protetor e da memória imunológica pela utilização do adjuvante CAF01 associado a antígenos totais de Leishmania amazonensis (LaAg) pela via intranasal contra a Leishmaniose visceral murina |
title |
Potencialização do efeito protetor e da memória imunológica pela utilização do adjuvante CAF01 associado a antígenos totais de Leishmania amazonensis (LaAg) pela via intranasal contra a Leishmaniose visceral murina |
spellingShingle |
Potencialização do efeito protetor e da memória imunológica pela utilização do adjuvante CAF01 associado a antígenos totais de Leishmania amazonensis (LaAg) pela via intranasal contra a Leishmaniose visceral murina Leal, Janine Miranda Memória imunológica Administração intranasal Leishmania chagasi Imunização intranasal Resposta imune Doenças Infecciosas e Parasitárias Leishmaniose visceral Memória - Imunologia 61 |
title_short |
Potencialização do efeito protetor e da memória imunológica pela utilização do adjuvante CAF01 associado a antígenos totais de Leishmania amazonensis (LaAg) pela via intranasal contra a Leishmaniose visceral murina |
title_full |
Potencialização do efeito protetor e da memória imunológica pela utilização do adjuvante CAF01 associado a antígenos totais de Leishmania amazonensis (LaAg) pela via intranasal contra a Leishmaniose visceral murina |
title_fullStr |
Potencialização do efeito protetor e da memória imunológica pela utilização do adjuvante CAF01 associado a antígenos totais de Leishmania amazonensis (LaAg) pela via intranasal contra a Leishmaniose visceral murina |
title_full_unstemmed |
Potencialização do efeito protetor e da memória imunológica pela utilização do adjuvante CAF01 associado a antígenos totais de Leishmania amazonensis (LaAg) pela via intranasal contra a Leishmaniose visceral murina |
title_sort |
Potencialização do efeito protetor e da memória imunológica pela utilização do adjuvante CAF01 associado a antígenos totais de Leishmania amazonensis (LaAg) pela via intranasal contra a Leishmaniose visceral murina |
author |
Leal, Janine Miranda |
author_facet |
Leal, Janine Miranda |
author_role |
author |
dc.contributor.advisor1.fl_str_mv |
Gomes, Daniel Cláudio de Oliveira |
dc.contributor.author.fl_str_mv |
Leal, Janine Miranda |
dc.contributor.referee1.fl_str_mv |
Rodrigues, Rodrigo Ribeiro |
dc.contributor.referee2.fl_str_mv |
Silva, Eduardo de Almeida Marques da |
contributor_str_mv |
Gomes, Daniel Cláudio de Oliveira Rodrigues, Rodrigo Ribeiro Silva, Eduardo de Almeida Marques da |
dc.subject.por.fl_str_mv |
Memória imunológica Administração intranasal Leishmania chagasi Imunização intranasal Resposta imune |
topic |
Memória imunológica Administração intranasal Leishmania chagasi Imunização intranasal Resposta imune Doenças Infecciosas e Parasitárias Leishmaniose visceral Memória - Imunologia 61 |
dc.subject.cnpq.fl_str_mv |
Doenças Infecciosas e Parasitárias |
dc.subject.br-rjbn.none.fl_str_mv |
Leishmaniose visceral Memória - Imunologia |
dc.subject.udc.none.fl_str_mv |
61 |
description |
The dimethyldioctadecylammonium (DDA) is a quaternary ammonium compound formed by a synthetic amphiphilic lipid comprising a hydrophilic positively charged dimethylammonium head–group attached to two hydrophobic 18-carbon alkyl chains (tail), that has previously been reported for eliciting cell-mediated and humoral responses against pathogens like Mycobacterium tuberculosis and Chlamydia trachomatis. In the present study, we investigated the ability of CAF adjuvant associated with surface antigens of Leishmania amazonensis (LaAg) to induce immunogenic and protective responses in challenge against L. chagasi. So, BALB/c mice were vaccinated by intranasal route with 2 doses of LaAg (25 mg) or LaAg associated with CAF (150 mg) intercalated by 15 days. The measurement of transaminases and creatinine in the animals sera demonstrated the biocompatibility and safety of the LaAg/CAF combination. Besides, IFN-γ and NO produced by splenocytes after LaAg in vitro recall was significantly increased, beyond significantly lymphoproliferative responses and increase of memory cells (TCD4+ CD44+ CD62L+) percentage. Increased IgG and specific subclasses (IgG1 and IgG2a) in sera levels were also observed in mice vaccinated with LaAg associated with CAF when compared to controls. Similarly, animals vaccinated with this formulation and challenged with L. chagasi 15 days after the booster with L. chagasi showed a significant decrease in parasite load in the spleen and liver, associated with increased production of IFN-γ and increased lymphoproliferative responses. Together, our results demonstrate for the first time the feasibility of intranasal vaccine with LaAg/CAF as a effective mechanism for the vaccination against visceral leishmaniasis. |
publishDate |
2014 |
dc.date.submitted.none.fl_str_mv |
2014-07-11 |
dc.date.issued.fl_str_mv |
2014-07-11 |
dc.date.accessioned.fl_str_mv |
2015-11-16T17:32:12Z |
dc.type.status.fl_str_mv |
info:eu-repo/semantics/publishedVersion |
dc.type.driver.fl_str_mv |
info:eu-repo/semantics/masterThesis |
format |
masterThesis |
status_str |
publishedVersion |
dc.identifier.uri.fl_str_mv |
http://repositorio.ufes.br/handle/10/1595 |
url |
http://repositorio.ufes.br/handle/10/1595 |
dc.language.iso.fl_str_mv |
por |
language |
por |
dc.rights.driver.fl_str_mv |
info:eu-repo/semantics/openAccess |
eu_rights_str_mv |
openAccess |
dc.format.none.fl_str_mv |
Text |
dc.publisher.none.fl_str_mv |
Universidade Federal do Espírito Santo Mestrado em Doenças Infecciosas |
dc.publisher.program.fl_str_mv |
Programa de Pós-Graduação em Doenças Infecciosas |
dc.publisher.initials.fl_str_mv |
UFES |
dc.publisher.country.fl_str_mv |
BR |
dc.publisher.department.fl_str_mv |
Centro de Ciências da Saúde |
publisher.none.fl_str_mv |
Universidade Federal do Espírito Santo Mestrado em Doenças Infecciosas |
dc.source.none.fl_str_mv |
reponame:Repositório Institucional da Universidade Federal do Espírito Santo (riUfes) instname:Universidade Federal do Espírito Santo (UFES) instacron:UFES |
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Universidade Federal do Espírito Santo (UFES) |
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UFES |
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UFES |
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Repositório Institucional da Universidade Federal do Espírito Santo (riUfes) |
collection |
Repositório Institucional da Universidade Federal do Espírito Santo (riUfes) |
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