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Comparison between the use of different APCs transfected in vitro with Mycobacterium leprae hsp65 gene, with the message or with the protein as a new vaccination strategy and therapy against tuberculosis

Grant number: 06/01242-4
Support type:Scholarships in Brazil - Doctorate
Effective date (Start): February 01, 2007
Effective date (End): August 31, 2009
Field of knowledge:Biological Sciences - Immunology - Applied Immunology
Principal researcher:Arlete Aparecida Martins Coelho-Castelo
Grantee:Carolina Damas Rocha
Home Institution: Faculdade de Medicina de Ribeirão Preto (FMRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil

Abstract

The naked DNA vaccine enconding the heat-shock protein of 65 kDa of Mycobacterium leprae presents a prophylactic and therapeutic effect in an experimental model of tuberculosis. Some results also showed that after intramuscular immunization, DNA-hsp65 could be detected in dendritic cells and lymphocyte B, from lymph node and bone marrow, suggesting B cells can also participate as APC in induction of immune response, in DNA vaccine models. It was the first observation that B cells can be involved in this process and supports part of the project. Furthermore, despite DNA vaccine success in experimental models, and that no one collateral effect was detected until this time, some questions related with safety can be an obstacle to a broad use of this strategy. In order to avoid possible risks in DNA vaccine models, some alternatives have being tested like transference of transfected cells with mRNA. Transfection with mRNA is a safe and efficient method of delivering antigens to antigen-presenting cells (APCs). Immunization of dendritic cells transfected with different mRNA is currently being tested. In order to evaluate new vaccine approaches and understand the lymphocyte B role as antigen-presenting cells during experimental models of genetic vaccines this project propose to evaluate the function of three different APC in immunogenicity, protection and therapy against experimental tuberculosis. So do that, mice will be immunized with dendritic cell, B cell or macrophage transfected with mRNA-hsp65 or hsp65 recombinant protein. The results obtained from these distinct strategies an offer a new and promising approach in preventing infectious diseases as tuberculosis.

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