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Immunochemotherapy for visceral leishmaniasis: combinatorial action of Miltefosine plus LBSapMPL vaccine improves adaptative Th1 immune response with control of splenic parasitism in experimental hamster model

Published online by Cambridge University Press:  02 November 2021

Lívia Mendes Carvalho ,
Miriã Rodrigues Gusmão ,
Ana Flávia Pereira Costa ,
Rory Cristiane Fortes de Brito ,
Rodrigo Dian de Oliveira Aguiar-Soares ,
Jamille Mirelle de Oliveira Cardoso ,
Alexandre Barbosa Reis Open the ORCID record for Alexandre Barbosa Reis [Opens in a new window] ,
Cláudia Martins Carneiro  and
Bruno Mendes Roatt Open the ORCID record for Bruno Mendes Roatt [Opens in a new window]
Lívia Mendes Carvalho
Affiliation:
Laboratório de Imunopatologia, Núcleo de Pesquisas em Ciências Biológicas/NUPEB, Universidade Federal de Ouro Preto, Ouro Preto, Minas Gerais, Brasil
Miriã Rodrigues Gusmão
Affiliation:
Laboratório de Imunopatologia, Núcleo de Pesquisas em Ciências Biológicas/NUPEB, Universidade Federal de Ouro Preto, Ouro Preto, Minas Gerais, Brasil
Ana Flávia Pereira Costa
Affiliation:
Laboratório de Imunopatologia, Núcleo de Pesquisas em Ciências Biológicas/NUPEB, Universidade Federal de Ouro Preto, Ouro Preto, Minas Gerais, Brasil
Rory Cristiane Fortes de Brito
Affiliation:
Laboratório de Imunopatologia, Núcleo de Pesquisas em Ciências Biológicas/NUPEB, Universidade Federal de Ouro Preto, Ouro Preto, Minas Gerais, Brasil
Rodrigo Dian de Oliveira Aguiar-Soares
Affiliation:
Laboratório de Imunopatologia, Núcleo de Pesquisas em Ciências Biológicas/NUPEB, Universidade Federal de Ouro Preto, Ouro Preto, Minas Gerais, Brasil
Jamille Mirelle de Oliveira Cardoso
Affiliation:
Laboratório de Imunopatologia, Núcleo de Pesquisas em Ciências Biológicas/NUPEB, Universidade Federal de Ouro Preto, Ouro Preto, Minas Gerais, Brasil
Alexandre Barbosa Reis
Affiliation:
Laboratório de Imunopatologia, Núcleo de Pesquisas em Ciências Biológicas/NUPEB, Universidade Federal de Ouro Preto, Ouro Preto, Minas Gerais, Brasil Instituto Nacional de Ciência e Tecnologia em Doenças Tropicais, Salvador, Bahia, Brazil
Cláudia Martins Carneiro
Affiliation:
Laboratório de Imunopatologia, Núcleo de Pesquisas em Ciências Biológicas/NUPEB, Universidade Federal de Ouro Preto, Ouro Preto, Minas Gerais, Brasil
Bruno Mendes Roatt*
Affiliation:
Laboratório de Imunopatologia, Núcleo de Pesquisas em Ciências Biológicas/NUPEB, Universidade Federal de Ouro Preto, Ouro Preto, Minas Gerais, Brasil Instituto Nacional de Ciência e Tecnologia em Doenças Tropicais, Salvador, Bahia, Brazil Departamento de Ciências Biológicas, Instituto de Ciências Exatas e Biológicas, Universidade Federal de Ouro Preto, Ouro Preto, Minas Gerais, Brazil
*
Author for correspondence: Bruno Mendes Roatt, E-mail: [email protected]
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Abstract

The control of human visceral leishmaniasis (VL) is hard since there are no vaccines available as well as the treatment is hampered by toxicity and resistant parasites. Furthermore, as human, and canine VL causes immunosuppression, the combination of drugs with immunostimulatory agents is interesting to upregulate the immunity, reducing side-effects, improving treatment approaches against disease. Herein, we assessed the immunochemotherapy using miltefosine along with a vaccine formulated by Leishmania braziliensis antigens + saponin + monophosphoryl lipid-A (LBSapMPL) in L. infantum-infected hamsters. Two months after infection, the animals received treatments, and after 15 days they were evaluated for the treatment effect. The potential anti-Leishmania effect of miltefosine + LBSapMPL-vaccine was revealed by a specific immune response activation reflecting in control of spleen parasitism using half the miltefosine treatment time. The treated animals also showed an increase of total and T-CD4 splenocytes producing IFN-γ and TNF-α and a decrease of interleukin-10 and anti-Leishmania circulating IgG. In addition, it was demonstrated that the control of spleen parasitism is related to the generation of a protective Th1 immune response. Hence, due to the combinatorial action of miltefosine with LBSapMPL-vaccine in immunostimulating and controlling parasitism, this immunochemotherapy protocol can be an important alternative option against canine and human VL.

Keywords

HamsterimmunochemotherapyLBSapMPL vaccineLeishmania infantummiltefosinevisceral leishmaniasis
Type
Research Article
Information
Parasitology , Volume 149 , Issue 3 , March 2022 , pp. 371 - 379
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Copyright
Copyright © The Author(s), 2021. Published by Cambridge University Press

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