New approaches using genetic material as a control to tuberculosis

摘要

Messenger RNA (mRNA) is highly versatile, non-toxic molecule that is easy to produce and store, which can allow transient protein expression in all cell types. The safety aspects of mRNA-based treatments in gene therapy make this molecule one of the most promising active components of therapeutic or prophylactic methods. The use of mRNA as strategy for the stimulation of the immune system has been used mainly in current strategies for the cancer treatment but until now there is no tested mRNA as vaccine for infectious disease. We produced mRNA of heat shock protein of 65-kDa (Hsp65) from Mycobacterium leprae and showed that vaccination of mice with a single dose of 10μg of naked mRNA-Hsp65 through intranasal route was able to induce protection against subsequent challenge with virulent strain of M. tuberculosis. In order to determine if antigen-presenting cells present in the lung are capable of capture the mRNA, labelled mRNA-Hsp65 was administered by intranasal route and then lung APCs were analyzed by flow cytometry. These experiments showed that after 30 minutes until 8 hours the populations of CD11c~+, CD11b~+ and CD19~+ cells were able to capture the mRNA. Taken together, our results showed a novel and promise strategy to control experimental tuberculosis.