Approximately 20 million people are living with Trypanosoma cruzi infection and 30-40 % of these are expected to develop clinical disease. T. cruzi infection poses two major challenges for physicians: how does one predict who will develop Chagas? disease (i.e. who would be treated), and how does one treat those individuals diagnosed with the chronic T. cruzi infection? In Project 3, we propose to investigate the potential for the development of therapeutic and transmission-blocking vaccines for T. cruzi. We have previously shown in mice andrecently confirmed in humans that the severity of disease is linked to the quality of the anti-parasite immune response. Furthermore, we have shown in preliminary experiments that vaccination of mice with the same cocktail of genes that provides prophylaxis from infection also decreases disease severity when delivered therapeutically. Projects 1 and 2 of the Program Project will generate raw materials needed for construction of an effective vaccine for T. cruzi. The goals of Project 3 are to investigate how best to deploy this vaccine.
Aim 1 will define the optimal combination of genes for vaccination and will evaluate a select set of methods to optimize delivery of a multi-component vaccine.Optimization will rely heavily on DNA vaccination and inclusion of a limited set of vaccine adjuvants. Two virus systems, lentiviruses and alphaviruses will also be evaluated as adjuncts (in prime-boost regimens) or as alternatives to DNA vaccination.
Aim 2 of this project will explore the possibility of a transmission blocking vaccine by testing a cocktail vaccine shown to be highly effective in mice for its efficacy in reducing parasite load in dogs and reducing the transmission of parasites to insect vectors.Finally, Aim 3 will seek to determine the mechanisms of action of therapeutic vaccines in T. cruziinfection. Completion of this project will define the contents, utility and mechanism of action of atherapeutic vaccine for T. cruzi.
Showing the most recent 10 out of 32 publications
