Vaccination with mRNA of Mycobacterium leprae hsp65 as a novel vaccination strategy against experimental tuberculosis

Abstract

Previous studies of Brazilian Tuberculosis Research Network/FMRP-USP, have been shown that intramuscular vaccination with plasmid DNA coding hsp65 of Mycobacterium leprae (DNA-hsp65), is able to protect mice, guinea pig and cows against subsequent challenge with virulent M. tuberculosis strain. In addition this vaccine can also present a therapeutic effect, in pre-infected mice. 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. Among these problems there is the possibility of integration of DNA-Vaccine into host genome, the capacity of long term survive of DNA molecules into the host nuclei and the possibility of production of anti-DNA antibodies are the major concern. In this way the use of mRNA has been emerged as a novel genetic vaccine approach. The mRNA is directly translated in the host cytoplasm cell, without incoming into the nuclei. In spite of mRNA vaccination could be more secure and efficient, we propose in this project the evaluation of immunogenecity and protection against tuberculosis using mRNA of M. leprae hsp65 as vaccine. The results obtained can open a new perspective in genetic vaccine.