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Immunotherapy with plasmid DNA encoding mycobacterial hsp65 in association with chemotherapy is a more rapid and efficient form of treatment for tuberculosis in mice

Abstract

Tuberculosis (TB) remains a threat for public health, killing around 3 million people a year. Despite the fact that most cases can be cured with antibiotics, the treatment is long and patients relapse if chemotherapy is not continued for at least 6 months. Thus, a better characterization of the working principles of the immune system in TB and identification of new immunotherapeutic products for the development of shorter regimens of treatment are essential to achieve an effective management of this disease. In the present work, we demonstrate that immunotherapy with a plasmid DNA encoding the Mycobacterium leprae 65 kDa heat-shock protein (hsp65) in order to boost the efficiency of the immune system, is a valuable adjunct to antibacterial chemotherapy to shorten the duration of treatment, improve the treatment of latent TB infection and be effective against multidrug-resistant bacilli (MDR-TB). We also showed that the use of DNA-hsp65 alone or in combination with other drugs influence the pathway of the immune response or other types of inflammatory responses and should augment our ability to alter the course of immune response/inflammation as needed, evidencing an important target for immunization or drug intervention.

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Acknowledgements

We thank Izaíra T Brandão for technical assistance. This study was supported by Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP), Instituto do Milênio REDE TB and Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq).

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Silva, C., Bonato, V., Coelho-Castelo, A. et al. Immunotherapy with plasmid DNA encoding mycobacterial hsp65 in association with chemotherapy is a more rapid and efficient form of treatment for tuberculosis in mice. Gene Ther 12, 281–287 (2005). https://doi.org/10.1038/sj.gt.3302418

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