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.
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Date
2021
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Abstract
Visceral leishmaniasis (VL) is a serious and neglected disease present worldwide. Chemotherapy using pentavalent antimony (SbV) 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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Keywords
Leishmania infantum, Immunochemotherapy
Citation
CARVALHO, L. M. et al. 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. Current Research in Immunology, v. 2, p. 194-201, 2021. Disponível em: <https://www.sciencedirect.com/science/article/pii/S2590255521000202>. Acesso em: 11 out. 2022.