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Heterologous vaccine therapy associated with half course of Miltefosine promote activation of the proinflammatory response with control of splenic parasitism in a hamster model of visceral leishmaniasis

Visceral leishmaniasis (VL) is a serious and neglected disease present worldwide. Chemotherapy using pentavalent antimony (Sb(V)) is the most practical and inexpensive strategy available for the VL treatment today, however, it has high toxicity. Alternatively, other drugs are used as viable leishman...

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Autores principales: Carvalho, Lívia Mendes, Ferreira, Francielle Carvalho, Gusmão, Miriã Rodrigues, Costa, Ana Flávia Pereira, de Brito, Rory Cristiane Fortes, Aguiar-Soares, Rodrigo Dian de Oliveira, Reis, Alexandre Barbosa, Cardoso, Jamille Mirelle de Oliveira, Carneiro, Cláudia Martins, Roatt, Bruno Mendes
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Elsevier 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9040144/
https://www.ncbi.nlm.nih.gov/pubmed/35492387
http://dx.doi.org/10.1016/j.crimmu.2021.10.003
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author Carvalho, Lívia Mendes
Ferreira, Francielle Carvalho
Gusmão, Miriã Rodrigues
Costa, Ana Flávia Pereira
de Brito, Rory Cristiane Fortes
Aguiar-Soares, Rodrigo Dian de Oliveira
Reis, Alexandre Barbosa
Cardoso, Jamille Mirelle de Oliveira
Carneiro, Cláudia Martins
Roatt, Bruno Mendes
author_facet Carvalho, Lívia Mendes
Ferreira, Francielle Carvalho
Gusmão, Miriã Rodrigues
Costa, Ana Flávia Pereira
de Brito, Rory Cristiane Fortes
Aguiar-Soares, Rodrigo Dian de Oliveira
Reis, Alexandre Barbosa
Cardoso, Jamille Mirelle de Oliveira
Carneiro, Cláudia Martins
Roatt, Bruno Mendes
author_sort Carvalho, Lívia Mendes
collection PubMed
description Visceral leishmaniasis (VL) is a serious and neglected disease present worldwide. Chemotherapy using pentavalent antimony (Sb(V)) is the most practical and inexpensive strategy available for the VL treatment today, however, it has high toxicity. Alternatively, other drugs are used as viable leishmanicidal therapeutic options. Miltefosine is the only anti-leishmanial agent administered orally, however, it has been reducing its effectiveness. In this sense, there is no ideal therapy for VL since the drugs currently used trigger severe side effects causing discontinuation of treatment, which carries an imminent risk for the emergence of parasite resistance. With that, other therapeutic strategies are gaining prominence. Among them, immunotherapy and/or immunochemotherapy, which the activation/modulation of the immune system can redirect the host's immune response to an effective therapeutic result. Therefore, this work was designed to assess an immunochemotherapy protocol composed of half course of Miltefosine associated with LBSap vaccine (Milt+LBSap) using the hamster Mesocricetus auratus as an experimental model for VL treatment. When evaluating the main hematobiochemical, immunological and therapeutic efficacy parameters, it was demonstrated that the treatment with Milt+LBSap showed restoration of hematobiochemical condition and reduced serum levels of IgG-anti-Leishmania compared to animals infected non treated (INT). Beyond that, an increase in the number of CD4(+) lymphocytes producers of IFN-γ in relation to INT or to animals treated with miltefosine during 28 days, and TNF-α increased compared to INT were observed. Also, it was found a reduction of IL-10-production in relation to INT, or animals that received LBSap vaccine only, or miltefosine, following by a reduction in the splenic parasitic burden. These results demonstrate that the immunochemotherapy protocol used can stimulate the immune response, inducing an expressive cellular response sufficient to control spleen parasitism, standing out as a promising proposal for the VL treatment.
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spelling pubmed-90401442022-04-27 Heterologous vaccine therapy associated with half course of Miltefosine promote activation of the proinflammatory response with control of splenic parasitism in a hamster model of visceral leishmaniasis Carvalho, Lívia Mendes Ferreira, Francielle Carvalho Gusmão, Miriã Rodrigues Costa, Ana Flávia Pereira de Brito, Rory Cristiane Fortes Aguiar-Soares, Rodrigo Dian de Oliveira Reis, Alexandre Barbosa Cardoso, Jamille Mirelle de Oliveira Carneiro, Cláudia Martins Roatt, Bruno Mendes Curr Res Immunol Research Paper Visceral leishmaniasis (VL) is a serious and neglected disease present worldwide. Chemotherapy using pentavalent antimony (Sb(V)) is the most practical and inexpensive strategy available for the VL treatment today, however, it has high toxicity. Alternatively, other drugs are used as viable leishmanicidal therapeutic options. Miltefosine is the only anti-leishmanial agent administered orally, however, it has been reducing its effectiveness. In this sense, there is no ideal therapy for VL since the drugs currently used trigger severe side effects causing discontinuation of treatment, which carries an imminent risk for the emergence of parasite resistance. With that, other therapeutic strategies are gaining prominence. Among them, immunotherapy and/or immunochemotherapy, which the activation/modulation of the immune system can redirect the host's immune response to an effective therapeutic result. Therefore, this work was designed to assess an immunochemotherapy protocol composed of half course of Miltefosine associated with LBSap vaccine (Milt+LBSap) using the hamster Mesocricetus auratus as an experimental model for VL treatment. When evaluating the main hematobiochemical, immunological and therapeutic efficacy parameters, it was demonstrated that the treatment with Milt+LBSap showed restoration of hematobiochemical condition and reduced serum levels of IgG-anti-Leishmania compared to animals infected non treated (INT). Beyond that, an increase in the number of CD4(+) lymphocytes producers of IFN-γ in relation to INT or to animals treated with miltefosine during 28 days, and TNF-α increased compared to INT were observed. Also, it was found a reduction of IL-10-production in relation to INT, or animals that received LBSap vaccine only, or miltefosine, following by a reduction in the splenic parasitic burden. These results demonstrate that the immunochemotherapy protocol used can stimulate the immune response, inducing an expressive cellular response sufficient to control spleen parasitism, standing out as a promising proposal for the VL treatment. Elsevier 2021-11-05 /pmc/articles/PMC9040144/ /pubmed/35492387 http://dx.doi.org/10.1016/j.crimmu.2021.10.003 Text en © 2021 Published by Elsevier B.V. https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
spellingShingle Research Paper
Carvalho, Lívia Mendes
Ferreira, Francielle Carvalho
Gusmão, Miriã Rodrigues
Costa, Ana Flávia Pereira
de Brito, Rory Cristiane Fortes
Aguiar-Soares, Rodrigo Dian de Oliveira
Reis, Alexandre Barbosa
Cardoso, Jamille Mirelle de Oliveira
Carneiro, Cláudia Martins
Roatt, Bruno Mendes
Heterologous vaccine therapy associated with half course of Miltefosine promote activation of the proinflammatory response with control of splenic parasitism in a hamster model of visceral leishmaniasis
title Heterologous vaccine therapy associated with half course of Miltefosine promote activation of the proinflammatory response with control of splenic parasitism in a hamster model of visceral leishmaniasis
title_full Heterologous vaccine therapy associated with half course of Miltefosine promote activation of the proinflammatory response with control of splenic parasitism in a hamster model of visceral leishmaniasis
title_fullStr Heterologous vaccine therapy associated with half course of Miltefosine promote activation of the proinflammatory response with control of splenic parasitism in a hamster model of visceral leishmaniasis
title_full_unstemmed Heterologous vaccine therapy associated with half course of Miltefosine promote activation of the proinflammatory response with control of splenic parasitism in a hamster model of visceral leishmaniasis
title_short Heterologous vaccine therapy associated with half course of Miltefosine promote activation of the proinflammatory response with control of splenic parasitism in a hamster model of visceral leishmaniasis
title_sort heterologous vaccine therapy associated with half course of miltefosine promote activation of the proinflammatory response with control of splenic parasitism in a hamster model of visceral leishmaniasis
topic Research Paper
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9040144/
https://www.ncbi.nlm.nih.gov/pubmed/35492387
http://dx.doi.org/10.1016/j.crimmu.2021.10.003
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