Safety and preservation of cardiac function following therapeutic vaccination against Trypanosoma cruzi in rhesus macaques

Abstract

Background: Chronic Chagasic cardiomyopathy is responsible for a large disease burden in the Americas, and a therapeutic vaccine would be highly desirable. We tested the safety and efficacy of a therapeutic DNA vaccine encoding antigens TSA-1 and Tc24 for preventing cardiac alterations in experimentally infected macaques. A secondary objective was to evaluate the feasibility of detecting changes in cardiac alterations in these animals. Methods: Naïve rhesus macaques were infected with Trypanosoma cruzi and treated with three doses of DNA vaccines. Results: Blood cell counts and chemistry indicated that therapeutic vaccination was safe, as hepatic and renal function appeared unaffected by the vaccination and/or infection with T. cruzi. Electrocardiographic (ECG) recordings indicated that no marked arrhythmias developed up to 7 months post-infection. Univariate analysis of ECG parameters found no significant differences in any of these parameters between vaccinated and control macaques. However, linear discriminant analysis revealed that control macaques presented clear alterations in their ECG patterns at 7 months post-infection, indicative of the onset of conduction defects and cardiac alterations, and these changes were prevented in vaccine treated macaques. Conclusions: This is the first evidence that therapeutic vaccination against T. cruzi can prevent cardiac alterations in non-human primates, strengthening the rationale for developing a human vaccine against Chagas disease.

Keywords

• Chagas disease
• DNA vaccine
• Cardiomyopathy
• Non-human primates
• Electrocardiograph