A Replication-Limited Recombinant Mycobacterium bovis BCG vaccine against tuberculosis designed for human immunodeficiency virus-positive persons is safer and more efficacious than BCG.

Infection and Immunity
Michael V TulliusM A Horwitz

Abstract

Tuberculosis is the leading cause of death in AIDS patients, yet the current tuberculosis vaccine, Mycobacterium bovis bacillus Calmette-Guérin (BCG), is contraindicated for immunocompromised individuals, including human immunodeficiency virus-positive persons, because it can cause disseminated disease; moreover, its efficacy is suboptimal. To address these problems, we have engineered BCG mutants that grow normally in vitro in the presence of a supplement, are preloadable with supplement to allow limited growth in vivo, and express the highly immunoprotective Mycobacterium tuberculosis 30-kDa major secretory protein. The limited replication in vivo renders these vaccines safer than BCG in SCID mice yet is sufficient to induce potent cell-mediated and protective immunity in the outbred guinea pig model of pulmonary tuberculosis. In the case of one vaccine, rBCG(mbtB)30, protection was superior to that with BCG (0.3-log fewer CFU of M. tuberculosis in the lung [P < 0.04] and 0.6-log fewer CFU in the spleen [P = 0.001] in aerosol-challenged animals [means for three experiments]); hence, rBCG(mbtB)30 is the first live mycobacterial vaccine that is both more attenuated than BCG in the SCID mouse and more potent than BCG in the guin...Continue Reading

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Citations

Mar 9, 2011·Proceedings of the National Academy of Sciences of the United States of America·Michael V TulliusCelia W Goulding
Jun 22, 2013·The Journal of Infectious Diseases·P Vineel ReddyAnil K Tyagi
Aug 30, 2011·Journal of Bacteriology·Sivagami Sundaram ChavadiLuis E N Quadri
May 17, 2012·PLoS Pathogens·Tom H M Ottenhoff, Stefan H E Kaufmann
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Nov 20, 2013·The Journal of Infectious Diseases·P Vineel ReddyAnil K Tyagi
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