High-throughput serological follow-up of Chagas Disease patients treated with benznidazole and E1224 in a randomised, placebo-controlled trial: searching for early indicators of treatment success and failure

BRACCO L; BLUM B; AGÜERO F; TORRICO F; SOSA ESTANI, S; RICCI A; RIBEIRO I; GASCON J

Mar del Plata

Congreso; Reunión Anual de Sociedades de Biociencias SAIC . SAFE . SAB . SAP . AACyTAL . NANOMED-ar . HCS; 2019

SAIC . SAFE . SAB . SAP . AACyTAL . NANOMED-ar . HCS

During an infection, the immune system produces antibodies against pathogens. With time, the immune repertoires of infected individuals become specific to their clinical history and thus represent a rich source of diagnostic markers. Chagas Disease (CD) is caused by the protozoan parasite Trypanosoma cruzi. When developing new drugs, it would be advantageous to reduce the followup time in clinical trials. The current criteria for cure in CD is negativization of at least one of 3 independent samples by PCR or at least 2 serological tests. However PCR assays have low sensitivity and seroconversion is slow using standard assays that measure antibodies to several antigens at once. Recently a new drug was tested for CD. In this study, fosravuconazole (E1224) was tested alongside benznidazole (BZ) and a placebo (Torrico et al 2018). E1224 displayed a transient, suppressive effect on parasite clearance, whereas BZ showed early and sustained efficacy until 12 months of follow-up. Using high-density peptide arrays displaying ~400,000 peptides derived from a large collection of recently identified T. cruzi antigens, we assessed changes in individual antibody repertoires along time for 36 patients from the 3 main study arms (BZ, E1224, placebo). The antibody repertoire of each patient was analyzed at recruitment (0), end-of-treatment (day 65) and at the end of follow-up (12 months). A total of 108 serum samples were analyzed in duplicate to assess the dynamics of the antibody immune in response to drug treatments (or placebo). A preliminary analysis of the data allowed us to identify antigens that increased or decreased their signal in treatment groups and also a number of subjects that showed more or earlier changes in their serological profile in response to treatment. We will discuss advances in our aim to find candidate prognostic markers to follow-up CD patients in clinical trials.Torrico F et al (2018) Lancet Infectious Diseases 18: 419, DOI:10.1016/S1473-3099(17)30538-8