Nanoformulations with <i>Leishmania braziliensis</i> Antigens Triggered Controlled Parasite Burden in Vaccinated Golden Hamster (<i>Mesocricetus auratus</i>) against Visceral Leishmaniasis
Leishmaniasis is a widespread vector-borne disease in Brazil, with <i>Leishmania</i> (<i>Leishmania</i>) <i>infantum</i> as the primary etiological agent of visceral leishmaniasis (VL). Dogs are considered the main reservoir of this parasite, whose treatment in Br...
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| Format: | Article |
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MDPI AG
2022-10-01
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| Series: | Vaccines |
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| Online Access: | https://www.mdpi.com/2076-393X/10/11/1848 |
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| author | Jennifer Ottino Jaqueline Costa Leite Otoni Alves Melo-Júnior Marco Antonio Cabrera González Tatiane Furtado de Carvalho Giani Martins Garcia Maurício Azevedo Batista Patrícia Silveira Mariana Santos Cardoso Lilian Lacerda Bueno Ricardo Toshio Fujiwara Renato Lima Santos Paulo Ricardo de Oliveira Paes Denise Silveira-Lemos Olindo Assis Martins-Filho Alexsandro Sobreira Galdino Miguel Angel Chávez-Fumagalli Walderez Ornelas Dutra Vanessa Carla Furtado Mosqueira Rodolfo Cordeiro Giunchetti |
| author_facet | Jennifer Ottino Jaqueline Costa Leite Otoni Alves Melo-Júnior Marco Antonio Cabrera González Tatiane Furtado de Carvalho Giani Martins Garcia Maurício Azevedo Batista Patrícia Silveira Mariana Santos Cardoso Lilian Lacerda Bueno Ricardo Toshio Fujiwara Renato Lima Santos Paulo Ricardo de Oliveira Paes Denise Silveira-Lemos Olindo Assis Martins-Filho Alexsandro Sobreira Galdino Miguel Angel Chávez-Fumagalli Walderez Ornelas Dutra Vanessa Carla Furtado Mosqueira Rodolfo Cordeiro Giunchetti |
| author_sort | Jennifer Ottino |
| collection | DOAJ |
| description | Leishmaniasis is a widespread vector-borne disease in Brazil, with <i>Leishmania</i> (<i>Leishmania</i>) <i>infantum</i> 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 (<i>Mesocricetus auratus</i>) as an experimental model in an anti-<i>Leishmania</i> 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 <i>Leishmania braziliensis</i> 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-<i>Leishmania</i> 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 <i>q</i>PCR in the LBSap, LBPSmG, and LBPSmP groups, respectively. In this way, LBSap, LBPSmG, and LBPSmP formulations showed better results in vaccinated and <i>L. infantum</i>-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. |
| first_indexed | 2024-03-09T18:34:16Z |
| format | Article |
| id | doaj.art-78ae9abe0eb846b08babb8711a7784d0 |
| institution | Directory Open Access Journal |
| issn | 2076-393X |
| language | English |
| last_indexed | 2024-03-09T18:34:16Z |
| publishDate | 2022-10-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Vaccines |
| spelling | doaj.art-78ae9abe0eb846b08babb8711a7784d02023-11-24T07:13:39ZengMDPI AGVaccines2076-393X2022-10-011011184810.3390/vaccines10111848Nanoformulations with <i>Leishmania braziliensis</i> Antigens Triggered Controlled Parasite Burden in Vaccinated Golden Hamster (<i>Mesocricetus auratus</i>) against Visceral LeishmaniasisJennifer Ottino0Jaqueline Costa Leite1Otoni Alves Melo-Júnior2Marco Antonio Cabrera González3Tatiane Furtado de Carvalho4Giani Martins Garcia5Maurício Azevedo Batista6Patrícia Silveira7Mariana Santos Cardoso8Lilian Lacerda Bueno9Ricardo Toshio Fujiwara10Renato Lima Santos11Paulo Ricardo de Oliveira Paes12Denise Silveira-Lemos13Olindo Assis Martins-Filho14Alexsandro Sobreira Galdino15Miguel Angel Chávez-Fumagalli16Walderez Ornelas Dutra17Vanessa Carla Furtado Mosqueira18Rodolfo Cordeiro Giunchetti19Departamento de Parasitologia, Universidade Federal de Minas Gerais (UFMG), Belo Horizonte 31270-901, Minas Gerais, BrazilDepartamento de Morfologia, Universidade Federal de Minas Gerais (UFMG), Belo Horizonte 31270-901, Minas Gerais, BrazilDepartamento de Morfologia, Universidade Federal de Minas Gerais (UFMG), Belo Horizonte 31270-901, Minas Gerais, BrazilDepartamento de Morfologia, Universidade Federal de Minas Gerais (UFMG), Belo Horizonte 31270-901, Minas Gerais, BrazilEscola de Veterinária, Universidade Federal de Minas Gerais (UFMG), Belo Horizonte 31270-901, Minas Gerais, BrazilLaboratório de Desenvolvimento Galênico e Nanotecnologia, Escola de Farmácia, Universidade Federal de Ouro Preto (UFOP), Ouro Preto 35400-000, Minas Gerais, BrazilDepartamento de Morfologia, Universidade Federal de Minas Gerais (UFMG), Belo Horizonte 31270-901, Minas Gerais, BrazilDepartamento de Morfologia, Universidade Federal de Minas Gerais (UFMG), Belo Horizonte 31270-901, Minas Gerais, BrazilDepartamento de Parasitologia, Universidade Federal de Minas Gerais (UFMG), Belo Horizonte 31270-901, Minas Gerais, BrazilDepartamento de Parasitologia, Universidade Federal de Minas Gerais (UFMG), Belo Horizonte 31270-901, Minas Gerais, BrazilDepartamento de Parasitologia, Universidade Federal de Minas Gerais (UFMG), Belo Horizonte 31270-901, Minas Gerais, BrazilEscola de Veterinária, Universidade Federal de Minas Gerais (UFMG), Belo Horizonte 31270-901, Minas Gerais, BrazilEscola de Veterinária, Universidade Federal de Minas Gerais (UFMG), Belo Horizonte 31270-901, Minas Gerais, BrazilDepartamento de Morfologia, Universidade Federal de Minas Gerais (UFMG), Belo Horizonte 31270-901, Minas Gerais, BrazilCentro de Pesquisas René Rachou/Fundação Oswaldo Cruz, Belo Horizonte 30190-002, Minas Gerais, BrazilLaboratório de Biotecnologia de Microrganismos, Universidade Federal de São João Del-Rei (UFSJ), Campus Centro Oeste, Divinópolis 35501-296, Minas Gerais, BrazilComputational Biology and Chemistry Research Group, Vicerrectorado de Investigación, Universidad Católica de Santa María, Urb. San José S/N, Umacollo, Arequipa 04000, PeruDepartamento de Morfologia, Universidade Federal de Minas Gerais (UFMG), Belo Horizonte 31270-901, Minas Gerais, BrazilLaboratório de Desenvolvimento Galênico e Nanotecnologia, Escola de Farmácia, Universidade Federal de Ouro Preto (UFOP), Ouro Preto 35400-000, Minas Gerais, BrazilDepartamento de Parasitologia, Universidade Federal de Minas Gerais (UFMG), Belo Horizonte 31270-901, Minas Gerais, BrazilLeishmaniasis is a widespread vector-borne disease in Brazil, with <i>Leishmania</i> (<i>Leishmania</i>) <i>infantum</i> 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 (<i>Mesocricetus auratus</i>) as an experimental model in an anti-<i>Leishmania</i> 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 <i>Leishmania braziliensis</i> 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-<i>Leishmania</i> 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 <i>q</i>PCR in the LBSap, LBPSmG, and LBPSmP groups, respectively. In this way, LBSap, LBPSmG, and LBPSmP formulations showed better results in vaccinated and <i>L. infantum</i>-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.https://www.mdpi.com/2076-393X/10/11/1848visceral leishmaniasispolymeric nanoparticlevaccinehamsterpre-clinical trial |
| spellingShingle | Jennifer Ottino Jaqueline Costa Leite Otoni Alves Melo-Júnior Marco Antonio Cabrera González Tatiane Furtado de Carvalho Giani Martins Garcia Maurício Azevedo Batista Patrícia Silveira Mariana Santos Cardoso Lilian Lacerda Bueno Ricardo Toshio Fujiwara Renato Lima Santos Paulo Ricardo de Oliveira Paes Denise Silveira-Lemos Olindo Assis Martins-Filho Alexsandro Sobreira Galdino Miguel Angel Chávez-Fumagalli Walderez Ornelas Dutra Vanessa Carla Furtado Mosqueira Rodolfo Cordeiro Giunchetti Nanoformulations with <i>Leishmania braziliensis</i> Antigens Triggered Controlled Parasite Burden in Vaccinated Golden Hamster (<i>Mesocricetus auratus</i>) against Visceral Leishmaniasis Vaccines visceral leishmaniasis polymeric nanoparticle vaccine hamster pre-clinical trial |
| title | Nanoformulations with <i>Leishmania braziliensis</i> Antigens Triggered Controlled Parasite Burden in Vaccinated Golden Hamster (<i>Mesocricetus auratus</i>) against Visceral Leishmaniasis |
| title_full | Nanoformulations with <i>Leishmania braziliensis</i> Antigens Triggered Controlled Parasite Burden in Vaccinated Golden Hamster (<i>Mesocricetus auratus</i>) against Visceral Leishmaniasis |
| title_fullStr | Nanoformulations with <i>Leishmania braziliensis</i> Antigens Triggered Controlled Parasite Burden in Vaccinated Golden Hamster (<i>Mesocricetus auratus</i>) against Visceral Leishmaniasis |
| title_full_unstemmed | Nanoformulations with <i>Leishmania braziliensis</i> Antigens Triggered Controlled Parasite Burden in Vaccinated Golden Hamster (<i>Mesocricetus auratus</i>) against Visceral Leishmaniasis |
| title_short | Nanoformulations with <i>Leishmania braziliensis</i> Antigens Triggered Controlled Parasite Burden in Vaccinated Golden Hamster (<i>Mesocricetus auratus</i>) against Visceral Leishmaniasis |
| title_sort | nanoformulations with i leishmania braziliensis i antigens triggered controlled parasite burden in vaccinated golden hamster i mesocricetus auratus i against visceral leishmaniasis |
| topic | visceral leishmaniasis polymeric nanoparticle vaccine hamster pre-clinical trial |
| url | https://www.mdpi.com/2076-393X/10/11/1848 |
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