New immunochemotherapy schedules for leishmaniasis: association of the recombinant protein Ldcccys1 with allopurinol for treatment of visceral leishmaniasis and with the palladacycle complex DPPE 1.2 for treatment of cutaneous leishmaniasis.

• Grant number: 18/10373-2
• Support Opportunities: Regular Research Grants
• Start date: October 01, 2018
• End date: September 30, 2021
• Field of knowledge: Biological Sciences - Parasitology - Protozoology of Parasites
• Principal Investigator: Clara Lúcia Barbiéri Mestriner
• Grantee: Clara Lúcia Barbiéri Mestriner
• Host Institution: Escola Paulista de Medicina (EPM). Universidade Federal de São Paulo (UNIFESP). Campus São Paulo. São Paulo , SP, Brazil
• Associated researchers: Ieda Maria Longo Maugéri ; Katia Cristina Pereira Oliveira Santos

Abstract

Our previous data showed that the treatment of canine visceral leishmaniasis (CVL) with the recombinant cysteine proteinase from Leishmania (Leishmania) infantum chagasi, rLdccys1, plus Propionibacterium acnes as adjuvant resulted in immune protective responses and significant reduction of parasite load, control of disease development and increase of survival in treated dogs. Actually allopurinol is the main drug used for treatment of CVL, resulting in reduction of the clinical signs of the disease, as well as the decrease of parasite burden. However, cases of disease relapse following terminus of allopurinol therapy have been recorded which forces the extension of treatment indefinitely. Based on these data, one of the proposals of the present study is immunotherapy by use of rLdccys1 in association with allopurinol for the treatment of visceral leishmaniasis in hamster. In murine model, the treatment of cutaneous leishmaniasis caused by Leishmania (Leishmania) amazonensis with the palladacycle complex DPPE 1.2 resulted in a significant reduction of foot lesions at concentrations that are non toxic to the host. Furthermore, in mice the treatment with DPPE 1.2 was followed by immunomodulation with a predominance of inflammatory response. Preliminary results indicated that the treatment with DPPE 1.2 associated with rLdccys1 led to the amplification of the leishmanicidal effect of the palladacycle complex. In addition, recent data showed that the administration of DPPE 1.2 plus P. acnes to L. (L.) amazonensis-infected BALB/c mice led to a significant higher immune activation as well as to a higher parasite destruction compared to that observed in animals treated with DPPE 1.2 alone. Aiming to further amplify the leishmanicidal effect of DPPE 1.2, L. (L.) amazonensis-infected BALB/c mice will be treated with DPPE 1.2 associated with rLdccys1 plus P. acnes. In both proposed models of leishmaniasis it is expected that the protective immune response induced by rLdccys1 plus P. acnes potentiates the leishmanicidal action of allopurinol and DPPE 1.2, increasing the efficacy of these compounds for the disease treatment. (AU)