PROJECT SUMMARY
Non-inferiority trial of a therapeutic vaccine against Chagas disease in naturally-
infected rhesus macaques
Chagas disease is a major vector borne parasitic disease cause by the protozoan
parasite Trypanosoma cruzi, with over 6 million cases in the Americas. Chronic chagasic
cardiomyopathy (CCC) is the most common and life-threathening manifestation of
Chagas disease. There is a critical need to develop new treatments for Chagasic
patients, and vaccines would represent a very cost-effective alternative to drug therapy.
Preventive and therapeutic vaccines have shown promise in mouse and dog models, in
particular with vaccines based on TSA-1 and Tc24 parasite antigens. Therefore, our
long-term goal is to develop a human vaccine, to improve the prevention and control of
Chagas disease, and we have established a first public-private consortium to reach this
goal. The overall objective of the project is to evaluate the safety and efficacy of a
therapeutic vaccine against T. cruzi in non-human primates by performing a non-
inferiority trial in naturally infected rhesus macaques. Chagasic macaques will be
randomly assigned to treatments based on (a) our therapeutic vaccine alone, (b)
therapeutic vaccination plus subpatent benznidazole (BZN) treatment, for a non-
inferiority comparison with (c) the standard BZN drug treatment (comparator arm). We
will use blood parasitic load measured by qPCR, immediately (month 3) and 10 months
after treatment as a primary efficacy outcome, as in several current clinical trials. We will
test the hypothesis that therapeutic vaccination (alone or combined with BZN) is non-
inferior to conventional BZN treatment, immediately and 10 months after treatment. We
will also monitor cardiac function through electrocardiographic and echographic
recordings as a secondary outcome, to test the hypothesis that cardiac function can be
preserved by therapeutic vaccination. Finally, we will identify the immune correlates and
biomarkers for disease progression and response to treatments by associating
candidate molecules with cardiac function and parasite burden. Upon completion of
these studies, we expect to identify a leading vaccine candidate for future clinical trials,
which will lead to improved patient care and control of Chagas disease.
