Nanoformulations with Leishmania braziliensis Antigens Triggered Controlled Parasite Burden in Vaccinated Golden Hamster (Mesocricetus auratus) against Visceral Leishmaniasis

Detalhes bibliográficos
Autor(a) principal: Ottino, Jennifer
Data de Publicação: 2022
Outros Autores: Leite, Jaqueline Costa, Melo Júnior, Otoni Alves, González, Marco Antonio Cabrera, Carvalho, Tatiane Furtado de, Garcia, Giani Martins, Batista, Maurício Azevedo, Silveira, Patrícia, Cardoso, Mariana Santos, Bueno, Lilian Lacerda, Fujiwara, Ricardo Toshio, Santos, Renato Lima, Paes, Paulo Ricardo de Oliveira, Lemos, Denise Silveira, Martins Filho, Olindo Assis, Galdino, Alexsandro Sobreira, Chávez-Fumagalli, Miguel Angel, Dutra, Walderez Ornelas, Mosqueira, Vanessa Carla Furtado, Giunchetti, Rodolfo Cordeiro
Tipo de documento: Artigo
Idioma: eng
Título da fonte: Repositório Institucional da FIOCRUZ (ARCA)
Texto Completo: https://www.arca.fiocruz.br/handle/icict/56867
Resumo: Universidade Federal de Minas Gerais. Departamento de Parasitologia. Belo Horizonte, MG, Brazil.
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spelling Ottino, JenniferLeite, Jaqueline CostaMelo Júnior, Otoni AlvesGonzález, Marco Antonio CabreraCarvalho, Tatiane Furtado deGarcia, Giani MartinsBatista, Maurício AzevedoSilveira, PatríciaCardoso, Mariana SantosBueno, Lilian LacerdaFujiwara, Ricardo ToshioSantos, Renato LimaPaes, Paulo Ricardo de OliveiraLemos, Denise SilveiraMartins Filho, Olindo AssisGaldino, Alexsandro SobreiraChávez-Fumagalli, Miguel AngelDutra, Walderez OrnelasMosqueira, Vanessa Carla FurtadoGiunchetti, Rodolfo Cordeiro2023-02-03T18:28:29Z2023-02-03T18:28:29Z2022OTTINO, Jennifer et al. Nanoformulations with Leishmania braziliensis Antigens Triggered Controlled Parasite Burden in Vaccinated Golden Hamster (Mesocricetus auratus) against Visceral Leishmaniasis. Vaccines, v. 10. N. 11, 1848, 2022. doi: 10.3390/vaccines10111848.2076-393Xhttps://www.arca.fiocruz.br/handle/icict/56867engMDPI AGNanoformulations with Leishmania braziliensis Antigens Triggered Controlled Parasite Burden in Vaccinated Golden Hamster (Mesocricetus auratus) against Visceral Leishmaniasisinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleUniversidade Federal de Minas Gerais. Departamento de Parasitologia. Belo Horizonte, MG, Brazil.Universidade Federal de Minas Gerais. Departamento de Morfologia. Belo Horizonte, MG, Brazil.Universidade Federal de Minas Gerais. Departamento de Morfologia. Belo Horizonte, MG, Brazil.Universidade Federal de Minas Gerais. Departamento de Morfologia. Belo Horizonte, MG, Brazil/Universidade Federal de Ouro Preto. Escola de Farmácia. Laboratório de Desenvolvimento Galênico e Nanotecnologia. Ouro Preto, MG, Brazil/Instituto Nacional de Innovación Agraria. Estación Experimental Agraria Baños del Inca. Cajamarca, Peru.Universidade Federal de Minas Gerais. Escola de Veterinária. Belo Horizonte, MG, Brazil.Universidade Federal de Ouro Preto. Escola de Farmácia. Laboratório de Desenvolvimento Galênico e Nanotecnologia. Ouro Preto, MG, Brazil.Universidade Federal de Minas Gerais. Departamento de Morfologia. Belo Horizonte, MG, Brazil.Universidade Federal de Minas Gerais. Departamento de Morfologia. Belo Horizonte, MG, Brazil.Universidade Federal de Minas Gerais. Departamento de Parasitologia. Belo Horizonte, MG, Brazil.Universidade Federal de Minas Gerais. Departamento de Parasitologia. Belo Horizonte, MG, Brazil.Universidade Federal de Minas Gerais. Departamento de Parasitologia. Belo Horizonte, MG, Brazil.Universidade Federal de Minas Gerais. Escola de Veterinária. Belo Horizonte, MG, Brazil.Universidade Federal de Minas Gerais. Escola de Veterinária. Belo Horizonte, MG, Brazil.Universidade Federal de Minas Gerais. Departamento de Morfologia. Belo Horizonte, MG, Brazil.Fundação Oswaldo Cruz. Instituto René Rachou. Belo Horizonte, MG, Brazil.Universidade Federal de São João Del-Rei. Laboratório de Biotecnologia de Microrganismos.Divinópolis, MG, Brazil.Computational Biology and Chemistry Research Group. Vicerrectorado de Investigación. Universidad Católica de Santa María. Arequipa, Peru.Universidade Federal de Minas Gerais. Departamento de Morfologia. Belo Horizonte, MG, Brazil/ Instituto Nacional de Ciência e Tecnologia em Doenças Tropicais. Belo Horizonte, MG, Brazil.Universidade Federal de Ouro Preto. Escola de Farmácia. Laboratório de Desenvolvimento Galênico e Nanotecnologia. Ouro Preto, MG, Brazil.Universidade Federal de Minas Gerais. Departamento de Parasitologia. Belo Horizonte, MG, Brazil/Universidade Federal de Minas Gerais. Departamento de Morfologia. Belo Horizonte, MG, Brazil/Instituto Nacional de Ciência e Tecnologia em Doenças Tropicais. Belo Horizonte, MG, Brazil.Leishmaniasis is a widespread vector-borne disease in Brazil, with Leishmania (Leishmania) infantum as the primary etiological agent of visceral leishmaniasis (VL). Dogs are considered the main reservoir of this parasite, whose treatment in Brazil is restricted to the use of veterinary medicines, which do not promote a parasitological cure. Therefore, efficient vaccine development is the best approach to Canine Visceral Leishmaniasis (CVL) control. With this in mind, this study used hamsters (Mesocricetus auratus) as an experimental model in an anti-Leishmania preclinical vaccine trial to evaluate the safety, antigenicity, humoral response, and effects on tissue parasite load. Two novel formulations of nanoparticles made from poly(D, L-lactic) acid (PLA) polymer loading Leishmania braziliensis crude antigen (LB) exhibiting two different particle sizes were utilized: LBPSmG (570 nm) and LBPSmP (388 nm). The results showed that the nanoparticles were safe and harmless to hamsters and were antigenic with the induction in LBSap, LBPSmG, and LBPSmG groups of total anti-Leishmania IgG antibodies 30 days after challenge, which persists 200 days in LBSap and LBPSmP. At the same time, a less pronounced hepatosplenomegaly in LBSap, LBPSmG, and LBPSmP was found when compared to control groups, as well as a less pronounced inflammatory infiltrate and granuloma formation in the spleen. Furthermore, significant reductions of 84%, 81%, and 90% were observed in spleen parasite burden accessed by qPCR in the LBSap, LBPSmG, and LBPSmP groups, respectively. In this way, LBSap, LBPSmG, and LBPSmP formulations showed better results in vaccinated and L. infantum-challenged animals in further reducing parasitic load in the spleen and attenuating lesions in liver and splenic tissues. This results in safe, harmless nanoformulation vaccines with significant immunogenic and infection control potential. In addition, animals vaccinated with LBPSmP had an overall reduction in parasite burden in the spleen, indicating that a smaller nanoparticle could be more efficient in targeting antigen-presenting cells.hamsterpolymeric nanoparticlepre-clinical trialvaccinevisceral leishmaniasisinfo:eu-repo/semantics/openAccessreponame:Repositório Institucional da FIOCRUZ (ARCA)instname:Fundação Oswaldo Cruz (FIOCRUZ)instacron:FIOCRUZORIGINALNanoformulations with Leishmania braziliensis.pdfNanoformulations with Leishmania braziliensis.pdfapplication/pdf3997862https://www.arca.fiocruz.br/bitstream/icict/56867/2/Nanoformulations%20with%20Leishmania%20braziliensis.pdf88a2ae669d3b645fe7ccd80c8b7103f4MD52LICENSElicense.txtlicense.txttext/plain; charset=utf-82991https://www.arca.fiocruz.br/bitstream/icict/56867/1/license.txt5a560609d32a3863062d77ff32785d58MD51icict/568672023-02-03 15:28:30.046oai:www.arca.fiocruz.br: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ório 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dc.title.en_US.fl_str_mv Nanoformulations with Leishmania braziliensis Antigens Triggered Controlled Parasite Burden in Vaccinated Golden Hamster (Mesocricetus auratus) against Visceral Leishmaniasis
title Nanoformulations with Leishmania braziliensis Antigens Triggered Controlled Parasite Burden in Vaccinated Golden Hamster (Mesocricetus auratus) against Visceral Leishmaniasis
spellingShingle Nanoformulations with Leishmania braziliensis Antigens Triggered Controlled Parasite Burden in Vaccinated Golden Hamster (Mesocricetus auratus) against Visceral Leishmaniasis
Ottino, Jennifer
hamster
polymeric nanoparticle
pre-clinical trial
vaccine
visceral leishmaniasis
title_short Nanoformulations with Leishmania braziliensis Antigens Triggered Controlled Parasite Burden in Vaccinated Golden Hamster (Mesocricetus auratus) against Visceral Leishmaniasis
title_full Nanoformulations with Leishmania braziliensis Antigens Triggered Controlled Parasite Burden in Vaccinated Golden Hamster (Mesocricetus auratus) against Visceral Leishmaniasis
title_fullStr Nanoformulations with Leishmania braziliensis Antigens Triggered Controlled Parasite Burden in Vaccinated Golden Hamster (Mesocricetus auratus) against Visceral Leishmaniasis
title_full_unstemmed Nanoformulations with Leishmania braziliensis Antigens Triggered Controlled Parasite Burden in Vaccinated Golden Hamster (Mesocricetus auratus) against Visceral Leishmaniasis
title_sort Nanoformulations with Leishmania braziliensis Antigens Triggered Controlled Parasite Burden in Vaccinated Golden Hamster (Mesocricetus auratus) against Visceral Leishmaniasis
author Ottino, Jennifer
author_facet Ottino, Jennifer
Leite, Jaqueline Costa
Melo Júnior, Otoni Alves
González, Marco Antonio Cabrera
Carvalho, Tatiane Furtado de
Garcia, Giani Martins
Batista, Maurício Azevedo
Silveira, Patrícia
Cardoso, Mariana Santos
Bueno, Lilian Lacerda
Fujiwara, Ricardo Toshio
Santos, Renato Lima
Paes, Paulo Ricardo de Oliveira
Lemos, Denise Silveira
Martins Filho, Olindo Assis
Galdino, Alexsandro Sobreira
Chávez-Fumagalli, Miguel Angel
Dutra, Walderez Ornelas
Mosqueira, Vanessa Carla Furtado
Giunchetti, Rodolfo Cordeiro
author_role author
author2 Leite, Jaqueline Costa
Melo Júnior, Otoni Alves
González, Marco Antonio Cabrera
Carvalho, Tatiane Furtado de
Garcia, Giani Martins
Batista, Maurício Azevedo
Silveira, Patrícia
Cardoso, Mariana Santos
Bueno, Lilian Lacerda
Fujiwara, Ricardo Toshio
Santos, Renato Lima
Paes, Paulo Ricardo de Oliveira
Lemos, Denise Silveira
Martins Filho, Olindo Assis
Galdino, Alexsandro Sobreira
Chávez-Fumagalli, Miguel Angel
Dutra, Walderez Ornelas
Mosqueira, Vanessa Carla Furtado
Giunchetti, Rodolfo Cordeiro
author2_role author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
dc.contributor.author.fl_str_mv Ottino, Jennifer
Leite, Jaqueline Costa
Melo Júnior, Otoni Alves
González, Marco Antonio Cabrera
Carvalho, Tatiane Furtado de
Garcia, Giani Martins
Batista, Maurício Azevedo
Silveira, Patrícia
Cardoso, Mariana Santos
Bueno, Lilian Lacerda
Fujiwara, Ricardo Toshio
Santos, Renato Lima
Paes, Paulo Ricardo de Oliveira
Lemos, Denise Silveira
Martins Filho, Olindo Assis
Galdino, Alexsandro Sobreira
Chávez-Fumagalli, Miguel Angel
Dutra, Walderez Ornelas
Mosqueira, Vanessa Carla Furtado
Giunchetti, Rodolfo Cordeiro
dc.subject.en.en_US.fl_str_mv hamster
polymeric nanoparticle
pre-clinical trial
vaccine
visceral leishmaniasis
topic hamster
polymeric nanoparticle
pre-clinical trial
vaccine
visceral leishmaniasis
description Universidade Federal de Minas Gerais. Departamento de Parasitologia. Belo Horizonte, MG, Brazil.
publishDate 2022
dc.date.issued.fl_str_mv 2022
dc.date.accessioned.fl_str_mv 2023-02-03T18:28:29Z
dc.date.available.fl_str_mv 2023-02-03T18:28:29Z
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.citation.fl_str_mv OTTINO, Jennifer et al. Nanoformulations with Leishmania braziliensis Antigens Triggered Controlled Parasite Burden in Vaccinated Golden Hamster (Mesocricetus auratus) against Visceral Leishmaniasis. Vaccines, v. 10. N. 11, 1848, 2022. doi: 10.3390/vaccines10111848.
dc.identifier.uri.fl_str_mv https://www.arca.fiocruz.br/handle/icict/56867
dc.identifier.issn.en_US.fl_str_mv 2076-393X
identifier_str_mv OTTINO, Jennifer et al. Nanoformulations with Leishmania braziliensis Antigens Triggered Controlled Parasite Burden in Vaccinated Golden Hamster (Mesocricetus auratus) against Visceral Leishmaniasis. Vaccines, v. 10. N. 11, 1848, 2022. doi: 10.3390/vaccines10111848.
2076-393X
url https://www.arca.fiocruz.br/handle/icict/56867
dc.language.iso.fl_str_mv eng
language eng
dc.rights.driver.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.publisher.none.fl_str_mv MDPI AG
publisher.none.fl_str_mv MDPI AG
dc.source.none.fl_str_mv reponame:Repositório Institucional da FIOCRUZ (ARCA)
instname:Fundação Oswaldo Cruz (FIOCRUZ)
instacron:FIOCRUZ
instname_str Fundação Oswaldo Cruz (FIOCRUZ)
instacron_str FIOCRUZ
institution FIOCRUZ
reponame_str Repositório Institucional da FIOCRUZ (ARCA)
collection Repositório Institucional da FIOCRUZ (ARCA)
bitstream.url.fl_str_mv https://www.arca.fiocruz.br/bitstream/icict/56867/2/Nanoformulations%20with%20Leishmania%20braziliensis.pdf
https://www.arca.fiocruz.br/bitstream/icict/56867/1/license.txt
bitstream.checksum.fl_str_mv 88a2ae669d3b645fe7ccd80c8b7103f4
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bitstream.checksumAlgorithm.fl_str_mv MD5
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repository.name.fl_str_mv Repositório Institucional da FIOCRUZ (ARCA) - Fundação Oswaldo Cruz (FIOCRUZ)
repository.mail.fl_str_mv repositorio.arca@fiocruz.br
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