Evaluation of imiquimod loaded archaeosomes as potential immunotherapy for Chagas disease

BRUNO ALLIANI; PETRAY, PB; PARRA F; ROMERO EL; FRANK FM

Buenos Aires

Congreso; Reunión Conjunta de Sociedades de Biociencias; 2017

EVALUATION OF IMIQUIMOD LOADED ARCHAEOSOMES AS POTENTIAL IMMUNOTHERAPY FOR CHAGAS DISEASEParra FL, Alliani BF, Frank FM, Romero EL, Petray PBArchaeosomes prepared with ether lipids of Archaeobacteria constitute a novel family of liposome. They show high adjuvant activity and can be used as delivery system. We investigate the immunotherapeutic effect of imiquimod loaded archaeosomes (IMQ-ARC) against experimental T. cruzi infection. C3H/HeN mice were injected ip with trypomastigotes RA of T. cruzi and were administered with free IMQ (1 mg/kg), IMQ-ARC, empty ARC or PBS. Treatment was carried out sc on the back at day 0 and 7 post infection (pi). Other group received BZ (100 mg/kg/day) by gavage as reference therapy for 14 consecutive days. Parasitemia, body weight and mortality were registered. Survival mice were euthanized at 60 dpi and serum samples were obtained to evaluate the serological profile. Fragments of heart and skeletal muscle were collected for histopathological analysis. The results showed that treatment with IMQ-ARC provoked a significant decrease (p=0.04) in parasitemia levels compared with those recorded in PBS controls. Administration of an equivalent amount of empty ARC or free IMQ had no effect on the parasitemia. All mice receiving immunotherapy lost weigh near máximum parasitemia. However, IMQ-ARC group showed lower weight loss compared with IMQ, ARC and PBS groups and at the end of experimental period reached weight values comparable to BZ group. A significant difference in mortality rates (p=0.03) between IMQ-ARC group and controls was seen. While all animals treated with IMQ-ARC survived until the end of the experiment, animals receiving free IMQ, empty ARC or PBS succumbed between days 20 and 33 pi. Mice receiving BZ survived without developing detectable parasitemia.The analysis of IgG isotype profiles revealed a mixed IgG1/IgG2a antibody pattern. Ongoing histopathological assays will help to evaluate the inflammatory process and tisular parasitism. In conclusion, IMQ-ARC may represent a potential adjuvant therapy to reduce the toxicity and side effects associated with the treatment of Chagas disease.