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

被引：4

作者：

Carvalho, Livia Mendes ^{[1
]}

Gusmao, Miria Rodrigues ^{[1
]}

Costa, Ana Flavia Pereira ^{[1
]}

de Brito, Rory Cristiane Fortes ^{[1
]}

Aguiar-Soares, Rodrigo Dian de Oliveira ^{[1
]}

Cardoso, Jamille Mirelle de Oliveira ^{[1
]}

Reis, Alexandre Barbosa ^{[1
,2
]}

Carneiro, Claudia Martins ^{[1
]}

Roatt, Bruno Mendes ^{[1
,2
,3
]}

机构：

[1] Univ Fed Ouro Preto, Nucleo Pesquisas Ciencias Biol NUPEB, Lab Imunopatol, Ouro Preto, MG, Brazil

[2] Inst Nacl Ciencia & Tecnol Doencas Trop, Salvador, BA, Brazil

[3] Univ Fed Ouro Preto, Dept Ciencias Biol, Inst Ciencias Exatas & Biol, Ouro Preto, MG, Brazil

来源：

PARASITOLOGY | 2022年 / 149卷 / 03期

关键词：

Hamster; immunochemotherapy; LBSapMPL vaccine; Leishmania infantum; miltefosine; visceral leishmaniasis; DONOVANI; IMMUNOTHERAPY; CHEMOTHERAPY; DISCOVERY; EFFICACY; PATTERNS; INFANTUM;

D O I：

10.1017/S0031182021001906

中图分类号：

R38 [医学寄生虫学]; Q [生物科学];

学科分类号：

07 ; 0710 ; 09 ; 100103 ;

摘要：

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-gamma and TNF-alpha 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.

引用

页码：371 / 379

页数：9

共 41 条

[1] Can We Harness Immune Responses to Improve Drug Treatment in Leishmaniasis? [J].

Aruleba, Raphael Taiwo ;

Carter, Katharine C. ;

Brombacher, Frank ;

Hurdayal, Ramona .

MICROORGANISMS, 2020, 8 (07) :1-20

[2] Immunotherapy with the saponin enriched-Leishmune® vaccine versus immunochemotherapy in dogs with natural canine visceral leishmaniasis [J].

Borja-Cabrera, G. P. ;

Santos, F. N. ;

Santos, F. B. ;

Trivellato, Fernando Antonio de A. ;

Kawasaki, Jarbas Kiyoshi A. ;

Costa, Andreia Cerqueira ;

Castro, Tatiana ;

Nogueira, F. S. ;

Moreira, M. A. B. ;

Luvizotto, M. C. R. ;

Palatnik, M. ;

Palatnik-de-Sousa, C. B. .

VACCINE, 2010, 28 (03) :597-603

[3] Natural Resistance of Leishmania infantum to Miltefosine Contributes to the Low Efficacy in the Treatment of Visceral Leishmaniasis in Brazil [J].

Carnielli, Juliana B. T. ;

Monti-Rocha, Renata ;

Costa, Dorcas Lamounier ;

Sesana, Aretha Molina ;

Pansini, Laura N. N. ;

Segatto, Marcela ;

Mottram, Jeremy C. ;

Nery Costa, Carlos Henrique ;

Carvalho, Silvio F. G. ;

Dietze, Reynaldo .

AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE, 2019, 101 (04) :789-794

[4] Establishment of monoclonal antibodies to evaluate the cellular immunity in a hamster model of L infantum infection [J].

Carvalho, Livia Mendes ;

de Brito, Rory Cristiane Fortes ;

Gusmao, Miria Rodrigues ;

de Oliveira Aguiar-Soares, Rodrigo Dian ;

Reis, Alexandre Barbosa ;

Roatt, Bruno Mendes .

PARASITE IMMUNOLOGY, 2021, 43 (04)

[5] THE ACTIVITY OF ALKYL PHOSPHORYLCHOLINES AND RELATED DERIVATIVES AGAINST LEISHMANIA-DONOVANI [J].

CROFT, SL ;

NEAL, RA ;

PENDERGAST, W ;

CHAN, JH .

BIOCHEMICAL PHARMACOLOGY, 1987, 36 (16) :2633-2636

[6] LEISHMANICIDAL ACTIVITY in vivo OF A MILTEFOSINE DERIVATIVE IN Mesocricetus auratus [J].

da Silva, Joana C. ;

Nunes, Juliana B. ;

Gontijo, Vanessa S. ;

Malaquias, Luiz Cosme C. ;

de Freitas, Rossimiriam P. ;

Alves, Rosemeire B. ;

Colombo, Fabio A. ;

Laurenti, Marcia D. ;

Marques, Marcos J. .

ACTA TROPICA, 2020, 209

[7] Cytokines: Key Determinants of Resistance or Disease Progression in Visceral Leishmaniasis: Opportunities for Novel Diagnostics and Immunotherapy [J].

Dayakar, Alti ;

Chandrasekaran, Sambamurthy ;

Kuchipudi, Suresh V. ;

Kalangi, Suresh K. .

FRONTIERS IN IMMUNOLOGY, 2019, 10

[8] Early high avidity specific IgG production in experimental hamster visceral leishmaniasis [J].

de Carvalho, Camila Aparecida ;

Ferrao, Thiago Fidelis ;

Cavalcante, Fernanda Siqueira ;

Novais de Freitas, Flavia Regina ;

Meireles, Luciana Regina ;

de Andrade Junior, Heitor Franco .

PARASITOLOGY RESEARCH, 2020, 119 (11) :3881-3885

[9] Molecular detection of infection homogeneity and impact of miltefosine treatment in a Syrian golden hamster model of Leishmania donovani and L. infantum visceral leishmaniasis [J].

Eberhardt, Eline ;

Mondelaers, Annelies ;

Hendrickx, Sarah ;

Van den Kerkhof, Magali ;

Maes, Louis ;

Caljon, Guy .

PARASITOLOGY RESEARCH, 2016, 115 (10) :4061-4070

[10] Visceral leishmaniasis treatment: What do we have, what do we need and how to deliver it? [J].

Freitas-Junior, Lucio H. ;

Chatelain, Eric ;

Kim, Helena Andrade ;

Siqueira-Neto, Jair L. .

INTERNATIONAL JOURNAL FOR PARASITOLOGY-DRUGS AND DRUG RESISTANCE, 2012, 2 :11-19

← 1 2 3 4 5 →