Challenging chronically infected mice with homologous Trypanosoma cruzi parasites enhances the immune response but does not modify cardiopathy: Implications for the design of a therapeutic vaccine. Clinical and Vaccine Immunology, vol 20, Número 2, pp 248

• Grant number: 13/02417-6
• Support Opportunities: Regular Research Grants - Publications - Scientific article
• Start date: April 01, 2013
• End date: September 30, 2013
• Field of knowledge: Biological Sciences - Immunology - Cellular Immunology
• Principal Investigator: José Maria Álvarez Mosig
• Grantee: José Maria Álvarez Mosig
• Host Institution: Instituto de Ciências Biomédicas (ICB). Universidade de São Paulo (USP). São Paulo , SP, Brazil

Abstract

Chagas disease is a Trypanosoma cruzi-induced zoonosis that has no natural cure. Local damage induced by the parasite and the immune response causes chronic heart and digestive lesions. Efforts to develop a therapeutic vaccine that boosts the immune response to completely clear the parasite are needed because there is no effective treatment for chronically infected patients. In an attempt to modify the host-parasite equilibrium toward increased parasite destruction, we analyzed cardiopathy and the immune response in chronically infected mice that were challenged with live homologous parasites. Challenge with a single dose of parasite increased CD4+ and CD8+ T cell populations, IFN-³ production and serum-specific IgG levels. However, subpatent parasitaemias and cardiac tissue were not affected. Because of the short breadth of the immune response after a single challenge we next evaluated the impact of four parasite doses, administered three weeks apart. One to two months after the last dose, the number of CD4+ T cells, IFN-³-producing CD4+ memory cells and CD4+ T cell proliferative response to T. cruzi antigen were increased in the spleen. The frequency of IFN-³-producing CD8+ memory cells in the blood was also increased. However, the sustained challenge did not favor TH1 development; rather it induced an increase in serum specific IgG1 levels and mixed TH1/TH2 cytokine production. Moreover, there were no significant changes in cardiac lesions and subpatent parasitaemias. In conclusion, we believe this study may help elucidating the necessary elements for a successful therapeutic vaccine which may reduce cardiomiopahty in chronically infected human patients. (AU)