Analysis of immune response profile induced by the vaccine epitope against Streptococcus pyogenes in peripheral blood samples of healthy individuals and rheumatic fever patients

• Grant number: 10/50405-9
• Support Opportunities: Regular Research Grants
• Start date: June 01, 2010
• End date: November 30, 2012
• Field of knowledge: Biological Sciences - Immunology
• Principal Investigator: Luiza Guglielmi
• Grantee: Luiza Guglielmi
• Host Institution: Instituto do Coração Professor Euryclides de Jesus Zerbini (INCOR). Hospital das Clínicas da Faculdade de Medicina da USP (HCFMUSP). Secretaria da Saúde (São Paulo - Estado). São Paulo , SP, Brazil

Abstract

Group A Streptococci (GAS) diseases remain as a major public health problem in development countries, reaching 600 million cases/year. GAS infections lead to severe invasive disease, pharyngitis and pioderma leading to autoimmune post-streptococcal sequels, such as Rheumatic Fever (RF) and Glomerulonephritis (GNDA). RF affects mainly children and teenagers. Rheumatic heart disease (RHD) is the most serious sequel of RF, leading to progressive and permanent valvular lesions. The worldwide incidence of RHD is at least 15.6 million cases and is responsible for 233,000 deaths/year. In Brazil, heart-valve damages due to RF are responsible for 90% of children heart surgeries and represent a very high cost to the Brazilian Healthy System. We are developing a vaccine against S. pyogenes based on both T and B protective epitopes of C-terminal portion of M protein. The vaccine epitope induced systemic protective immune response in murine models. Our aim is to evaluate how the anti-streptococcal vaccine model modulates the immune response through the analysis of expression profile of genes involved in innate and adaptive immune response such as Toll-like and chemokines receptors and ligands and proinflamatory cytokines and T cell subsets cytokines. We also intend to evaluate the capacity of the vaccine of induces T regulatory cells by using a collection of rheumatic heart-tissue infiltrating T-cells lines and clones obtained from RHD patients as well as peripheral blood of RF patients and healthy individuals stimulated in vitro with the vaccine epitope. The results of this work will contribute to evaluate the activation of the immune response induced by the vaccine as well as the protective capacity and safety. (AU)