Polymeric Delivery Systems as a Potential Vaccine against Visceral Leishmaniasis: Formulation Development and Immunogenicity

Recent studies suggest that the association of antigens in microparticles increases the anti-<i>Leishmania</i> vaccine immunogenicity. This study aims to investigate the in situ effect of the adjuvant performance consisting of chitosan-coated poly(<i>D</i>,<i>L</i>...

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Main Authors: João Guilherme Lino da Silva, Ana Alice Maia Gonçalves, Liliam Teixeira Oliveira, Giani Martins Garcia, Maurício Azevedo Batista, Ludmila Zanandreis de Mendonça, Kelvinson Fernandes Viana, Rita de Cássia Oliveira Sant’Ana, Otoni Alves de Oliveira Melo Júnior, Denise Silveira-Lemos, Walderez Ornelas Dutra, Olindo Assis Martins-Filho, Alexsandro Sobreira Galdino, Sandra Aparecida Lima de Moura, Vanessa Carla Furtado Mosqueira, Rodolfo Cordeiro Giunchetti
Format: Article
Language:English
Published: MDPI AG 2023-07-01
Series:Vaccines
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Online Access:https://www.mdpi.com/2076-393X/11/8/1309
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author João Guilherme Lino da Silva
Ana Alice Maia Gonçalves
Liliam Teixeira Oliveira
Giani Martins Garcia
Maurício Azevedo Batista
Ludmila Zanandreis de Mendonça
Kelvinson Fernandes Viana
Rita de Cássia Oliveira Sant’Ana
Otoni Alves de Oliveira Melo Júnior
Denise Silveira-Lemos
Walderez Ornelas Dutra
Olindo Assis Martins-Filho
Alexsandro Sobreira Galdino
Sandra Aparecida Lima de Moura
Vanessa Carla Furtado Mosqueira
Rodolfo Cordeiro Giunchetti
author_facet João Guilherme Lino da Silva
Ana Alice Maia Gonçalves
Liliam Teixeira Oliveira
Giani Martins Garcia
Maurício Azevedo Batista
Ludmila Zanandreis de Mendonça
Kelvinson Fernandes Viana
Rita de Cássia Oliveira Sant’Ana
Otoni Alves de Oliveira Melo Júnior
Denise Silveira-Lemos
Walderez Ornelas Dutra
Olindo Assis Martins-Filho
Alexsandro Sobreira Galdino
Sandra Aparecida Lima de Moura
Vanessa Carla Furtado Mosqueira
Rodolfo Cordeiro Giunchetti
author_sort João Guilherme Lino da Silva
collection DOAJ
description Recent studies suggest that the association of antigens in microparticles increases the anti-<i>Leishmania</i> vaccine immunogenicity. This study aims to investigate the in situ effect of the adjuvant performance consisting of chitosan-coated poly(<i>D</i>,<i>L</i>-lactic) acid submicrometric particles (SMP) and analyze the inflammatory profile and toxicity. Two formulations were selected, SMP<sup>1</sup>, containing poly(<i>D</i>,<i>L</i>-lactide) (PLA) 1% <i>wt</i>/<i>v</i> and chitosan 1% <i>wt</i>/<i>v</i>; and SMP<sup>2</sup>, containing PLA 5% <i>wt</i>/<i>v</i> and chitosan 5% <i>wt</i>/<i>v</i>. After a single dose of the unloaded SMP<sup>1</sup> or SMP<sup>2</sup> in mice, the SMPs promoted cell recruitment without tissue damage. In addition, besides the myeloperoxidase (MPO) activity having demonstrated similar results among the analyzed groups, a progressive reduction in the levels of N-acetyl-<i>β-<sub>D</sub></i>-glucosaminidase (NAG) until 72 h was observed for SMPs. While IL-6 levels were similar among all the analyzed groups along the kinetics, only the SMPs groups had detectable levels of TNF-α. Additionally, the <i>Leishmania braziliensis</i> antigen was encapsulated in SMPs (SMP<sup>1</sup>Ag and SMP<sup>2</sup>Ag), and mice were vaccinated with three doses. The immunogenicity analysis by flow cytometry demonstrated a reduction in NK (CD3<sup>−</sup>CD49<sup>+</sup>) cells in all the SMPs groups, in addition to impairment in the T cells subsets (CD3<sup>+</sup>CD4<sup>+</sup>) and CD3<sup>+</sup>CD8<sup>+</sup>) and B cells (CD19<sup>+</sup>) of the SMP<sup>2</sup> group. The resulting data demonstrate that the chitosan-coated SMP formulations stimulate the early events of an innate immune response, suggesting their ability to increase the immunogenicity of co-administered <i>Leishmania</i> antigens.
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spelling doaj.art-b192a37fcc4a4a2a96f6bbc049617eb42023-11-19T03:17:17ZengMDPI AGVaccines2076-393X2023-07-01118130910.3390/vaccines11081309Polymeric Delivery Systems as a Potential Vaccine against Visceral Leishmaniasis: Formulation Development and ImmunogenicityJoão Guilherme Lino da Silva0Ana Alice Maia Gonçalves1Liliam Teixeira Oliveira2Giani Martins Garcia3Maurício Azevedo Batista4Ludmila Zanandreis de Mendonça5Kelvinson Fernandes Viana6Rita de Cássia Oliveira Sant’Ana7Otoni Alves de Oliveira Melo Júnior8Denise Silveira-Lemos9Walderez Ornelas Dutra10Olindo Assis Martins-Filho11Alexsandro Sobreira Galdino12Sandra Aparecida Lima de Moura13Vanessa Carla Furtado Mosqueira14Rodolfo Cordeiro Giunchetti15Laboratory of Biology of Cell Interactions, Department of Morphology, Federal University of Minas Gerais (UFMG), Belo Horizonte 31270-901, BrazilLaboratory of Biology of Cell Interactions, Department of Morphology, Federal University of Minas Gerais (UFMG), Belo Horizonte 31270-901, BrazilLaboratory of Pharmaceutics and Nanotechnology (LDGNano), School of Pharmacy, Federal University of Ouro Preto, Ouro Preto 35400-000, BrazilLaboratory of Pharmaceutics and Nanotechnology (LDGNano), School of Pharmacy, Federal University of Ouro Preto, Ouro Preto 35400-000, BrazilLaboratory of Biology of Cell Interactions, Department of Morphology, Federal University of Minas Gerais (UFMG), Belo Horizonte 31270-901, BrazilLaboratory of Biology of Cell Interactions, Department of Morphology, Federal University of Minas Gerais (UFMG), Belo Horizonte 31270-901, BrazilLaboratory of Biology of Cell Interactions, Department of Morphology, Federal University of Minas Gerais (UFMG), Belo Horizonte 31270-901, BrazilLaboratory of Biology of Cell Interactions, Department of Morphology, Federal University of Minas Gerais (UFMG), Belo Horizonte 31270-901, BrazilLaboratory of Biology of Cell Interactions, Department of Morphology, Federal University of Minas Gerais (UFMG), Belo Horizonte 31270-901, BrazilIntegrated Research Group on Biomarkers, René Rachou Research Center, Oswaldo Cruz Foundation, Belo Horizonte 30190-009, BrazilLaboratory of Biology of Cell Interactions, Department of Morphology, Federal University of Minas Gerais (UFMG), Belo Horizonte 31270-901, BrazilLaboratory of Diagnosis and Monitoring Biomarkers, René Rachou Research Center, Oswaldo Cruz Foundation, Belo Horizonte 30190-009, BrazilLaboratory of Microorganism Biotechnology, Federal University of São João Del-Rei (UFSJ), Midwest Campus, Divinópolis 35501-296, BrazilLaboratory of Biomaterials and Experimental Pathology, Institute of Exact and Biological Sciences, Federal University of Ouro Preto, Ouro Preto 35402-136, BrazilLaboratory of Pharmaceutics and Nanotechnology (LDGNano), School of Pharmacy, Federal University of Ouro Preto, Ouro Preto 35400-000, BrazilLaboratory of Biology of Cell Interactions, Department of Morphology, Federal University of Minas Gerais (UFMG), Belo Horizonte 31270-901, BrazilRecent studies suggest that the association of antigens in microparticles increases the anti-<i>Leishmania</i> vaccine immunogenicity. This study aims to investigate the in situ effect of the adjuvant performance consisting of chitosan-coated poly(<i>D</i>,<i>L</i>-lactic) acid submicrometric particles (SMP) and analyze the inflammatory profile and toxicity. Two formulations were selected, SMP<sup>1</sup>, containing poly(<i>D</i>,<i>L</i>-lactide) (PLA) 1% <i>wt</i>/<i>v</i> and chitosan 1% <i>wt</i>/<i>v</i>; and SMP<sup>2</sup>, containing PLA 5% <i>wt</i>/<i>v</i> and chitosan 5% <i>wt</i>/<i>v</i>. After a single dose of the unloaded SMP<sup>1</sup> or SMP<sup>2</sup> in mice, the SMPs promoted cell recruitment without tissue damage. In addition, besides the myeloperoxidase (MPO) activity having demonstrated similar results among the analyzed groups, a progressive reduction in the levels of N-acetyl-<i>β-<sub>D</sub></i>-glucosaminidase (NAG) until 72 h was observed for SMPs. While IL-6 levels were similar among all the analyzed groups along the kinetics, only the SMPs groups had detectable levels of TNF-α. Additionally, the <i>Leishmania braziliensis</i> antigen was encapsulated in SMPs (SMP<sup>1</sup>Ag and SMP<sup>2</sup>Ag), and mice were vaccinated with three doses. The immunogenicity analysis by flow cytometry demonstrated a reduction in NK (CD3<sup>−</sup>CD49<sup>+</sup>) cells in all the SMPs groups, in addition to impairment in the T cells subsets (CD3<sup>+</sup>CD4<sup>+</sup>) and CD3<sup>+</sup>CD8<sup>+</sup>) and B cells (CD19<sup>+</sup>) of the SMP<sup>2</sup> group. The resulting data demonstrate that the chitosan-coated SMP formulations stimulate the early events of an innate immune response, suggesting their ability to increase the immunogenicity of co-administered <i>Leishmania</i> antigens.https://www.mdpi.com/2076-393X/11/8/1309visceral leishmaniasissubmicrometric particlesvaccinepolymeric nanoparticles
spellingShingle João Guilherme Lino da Silva
Ana Alice Maia Gonçalves
Liliam Teixeira Oliveira
Giani Martins Garcia
Maurício Azevedo Batista
Ludmila Zanandreis de Mendonça
Kelvinson Fernandes Viana
Rita de Cássia Oliveira Sant’Ana
Otoni Alves de Oliveira Melo Júnior
Denise Silveira-Lemos
Walderez Ornelas Dutra
Olindo Assis Martins-Filho
Alexsandro Sobreira Galdino
Sandra Aparecida Lima de Moura
Vanessa Carla Furtado Mosqueira
Rodolfo Cordeiro Giunchetti
Polymeric Delivery Systems as a Potential Vaccine against Visceral Leishmaniasis: Formulation Development and Immunogenicity
Vaccines
visceral leishmaniasis
submicrometric particles
vaccine
polymeric nanoparticles
title Polymeric Delivery Systems as a Potential Vaccine against Visceral Leishmaniasis: Formulation Development and Immunogenicity
title_full Polymeric Delivery Systems as a Potential Vaccine against Visceral Leishmaniasis: Formulation Development and Immunogenicity
title_fullStr Polymeric Delivery Systems as a Potential Vaccine against Visceral Leishmaniasis: Formulation Development and Immunogenicity
title_full_unstemmed Polymeric Delivery Systems as a Potential Vaccine against Visceral Leishmaniasis: Formulation Development and Immunogenicity
title_short Polymeric Delivery Systems as a Potential Vaccine against Visceral Leishmaniasis: Formulation Development and Immunogenicity
title_sort polymeric delivery systems as a potential vaccine against visceral leishmaniasis formulation development and immunogenicity
topic visceral leishmaniasis
submicrometric particles
vaccine
polymeric nanoparticles
url https://www.mdpi.com/2076-393X/11/8/1309
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