Live tuberculosis vaccines based on phoP mutants: a step towards clinical trials

Expert Opinion on Biological Therapy
J Gonzalo AsensioCarlos Martín

Abstract

Bacillus Calmette-Guérin (BCG) is the only preventive treatment for tuberculosis in humans, but this live vaccine confers variable protection against pulmonary tuberculosis in adults. Advances in the understanding of Mycobacterium tuberculosis immunopathogenesis have renewed hopes of developing new prophylactic vaccines conferring better protection than BCG. The authors describe here state-of-the-art attenuated live vaccines based on inactivation of the phoP gene, a transcriptional regulator of key virulence networks in M. tuberculosis. Recent preclinical testing of live vaccines based on phoP inactivation has demonstrated proof of concept, with a high degree of attenuation and protection against disease observed in various animal models. These results demonstrate that phoP mutants are promising new live vaccines for tuberculosis prevention. The steps that now need to be followed, to take these live vaccines towards clinical trials, are also reviewed, together with the potential of these vaccines to replace BCG.

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Citations

Sep 2, 2008·Journal of Bacteriology·Jesús Gonzalo-AsensioCarlos Martín
Sep 17, 2008·BMC Genomics·Andrea S LeungJun Liu
Oct 24, 2008·PloS One·Jesús Gonzalo-AsensioCarlos Martín
Oct 14, 2008·Expert Opinion on Biological Therapy·Pramod K Giri
Dec 22, 2012·Microbial Pathogenesis·Jonathan M PittAnne O'Garra
May 9, 2012·Trends in Immunology·Stefan H E Kaufmann
Jul 30, 2011·The Lancet Infectious Diseases·Stefan H E Kaufmann
Jun 21, 2011·Enfermedades infecciosas y microbiología clínica·Virgilio Bocanegra-GarcíaJosé Prisco Palma-Nicolás
May 18, 2010·Current Opinion in Immunology·Shreemanta K Parida, Stefan H E Kaufmann
Apr 26, 2011·Vaccine·Andrés Obregón-HenaoFabiana Bigi
Feb 1, 2014·Microbiology Spectrum·Tanya Parish

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