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Infection and Immunity, August 2005, p. 4676-4683, Vol. 73, No. 8
0019-9567/05/$08.00+0     doi:10.1128/IAI.73.8.4676-4683.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.

Enhancing the Protective Efficacy of Mycobacterium bovis BCG Vaccination against Tuberculosis by Boosting with the Mycobacterium tuberculosis Major Secretory Protein

Marcus A. Horwitz,* Günter Harth, Barbara Jane Dillon, and Sasa Maslesa-Galic

Department of Medicine, School of Medicine, University of California—Los Angeles, 10833 Le Conte Avenue, Los Angeles, California 90095

Received 12 January 2005/ Returned for modification 14 March 2005/ Accepted 23 March 2005

Tuberculosis continues to ravage humanity, killing 2 million people yearly. Most cases occur in areas of the world to which the disease is endemic, where almost everyone is vaccinated early in life with Mycobacterium bovis BCG, the currently available vaccine against tuberculosis. Thus, while more-potent vaccines are needed to replace BCG, new vaccines are also needed to boost the immune protection of the 4 billion people already vaccinated with BCG. Until now, no booster vaccine has been shown capable of significantly enhancing the level of protective immunity induced by BCG in the stringent guinea pig model of pulmonary tuberculosis, the "gold standard" for testing tuberculosis vaccines. In this paper, we describe a booster vaccine for BCG comprising the purified recombinant Mycobacterium tuberculosis 30-kDa protein, the major secreted protein of this pathogen. In the guinea pig model of pulmonary tuberculosis, boosting BCG-immunized animals once with the 30-kDa protein greatly increased cell-mediated and humoral immune responses to the protein in three consecutive experiments. Most importantly, boosting BCG-immunized animals once with the 30-kDa protein significantly enhanced protective immunity against aerosol challenge with highly virulent M. tuberculosis, as evidenced by a significantly reduced lung and spleen burden of M. tuberculosis compared with those for nonboosted BCG-immunized animals (mean additional reduction in CFU of 0.4 ± 0.1 log in the lung [P = 0.03] and 0.6 ± 0.1 log in the spleen [P = 0.002]). This study suggests that administering BCG-immunized people a booster vaccine comprising the 30-kDa protein may enhance their level of immunoprotection against tuberculosis.

* Corresponding author. Mailing address: Dept. of Medicine, CHS 37-121, School of Medicine, University of California, Los Angeles, 10833 Le Conte Ave., Los Angeles, CA 90095-1688. Phone: (310) 206-0074. Fax: (310) 794-7156. E-mail: mhorwitz{at}mednet.ucla.edu.

Editor: A. D. O'Brien

Infection and Immunity, August 2005, p. 4676-4683, Vol. 73, No. 8
0019-9567/05/$08.00+0     doi:10.1128/IAI.73.8.4676-4683.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Tullius, M. V., Harth, G., Maslesa-Galic, S., Dillon, B. J., Horwitz, M. A. (2008). A Replication-Limited Recombinant Mycobacterium bovis BCG Vaccine against Tuberculosis Designed for Human Immunodeficiency Virus-Positive Persons Is Safer and More Efficacious than BCG. Infect. Immun. 76: 5200-5214 [Abstract] [Full Text]  
  • Scott-Browne, J. P., Shafiani, S., Tucker-Heard, G., Ishida-Tsubota, K., Fontenot, J. D., Rudensky, A. Y., Bevan, M. J., Urdahl, K. B. (2007). Expansion and function of Foxp3-expressing T regulatory cells during tuberculosis. JEM 204: 2159-2169 [Abstract] [Full Text]  
  • Sable, S. B., Goyal, D., Verma, I., Behera, D., Khuller, G. K. (2007). Lung and blood mononuclear cell responses of tuberculosis patients to mycobacterial proteins. Eur Respir J 29: 337-346 [Abstract] [Full Text]  


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