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Advances in tuberculosis vaccine strategies

Nature Reviews Microbiology volume 4, pages 469–476 (2006)Cite this article

Abstract

Tuberculosis (TB), an ancient human scourge, is a growing health problem in the developing world. Approximately two million deaths each year are caused by TB, which is the leading cause of death in HIV-infected individuals. Clearly, an improved TB vaccine is desperately needed. Heterologous prime?boost regimens probably represent the best hope for an improved vaccine regimen to prevent TB. This first generation of new vaccines might also complement drug treatment regimens and be effective against reactivation of TB from the latent state, which would significantly enhance their usefulness.

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Figure 1: The immune response to Mycobacterium tuberculosis infection or vaccination with BCG or recombinant modified BCG.
Figure 2: Prime-boost vaccination strategies.

References

  1. Kochi, A. The global tuberculosis situation and the new control strategy of the World Health Organization 1991. Bull. World Health Organ. 79, 71?75 (2001).

    CAS  PubMed  PubMed Central  Google Scholar 

  2. Hopewell, P. C. Impact of human immunodeficiency virus infection on the epidemiology, clinical features, management and control of tuberculosis. Clin. Infect. Dis. 15, 540?547 (1992).

    CAS  PubMed  Google Scholar 

  3. Raviglione, M. C. et al. Tuberculosis trends in eastern Europe and the former USSR. Tuber. Lung Dis. 75, 400?416 (1994).

    CAS  PubMed  Google Scholar 

  4. Maher, D. et al. Tuberculosis deaths in countries with high HIV prevalence: what is their use as an indicator in tuberculosis programme monitoring and epidemiological surveillance? Int. J. Tuberc. Lung Dis. 9, 123?127 (2005).

    CAS  PubMed  Google Scholar 

  5. Bloom, B. R. & Fine, P. E. In Tuberculosis: Pathogenesis, Protection, and Control (ed. Bloom, B. R.) 531?557 (American Society for Microbiology, Washington DC, 1994).

    Google Scholar 

  6. Summary from the 6th Annual Conference of the International Union Against Tuberculosis and Lung Disease. (Chicago, 2001).

  7. Ormerod, L. P., Horsfield, N. & Green, R. M. Tuberculosis treatment outcome monitoring: Blackburn 1988?2000. Int. J. Tuberc. Lung Dis. 6, 662?665 (2002).

    CAS  PubMed  Google Scholar 

  8. Sudre, P., ten Dam, G. & Kochi, A. Tuberculosis: a global overview of the situation today. Bull. World Health Organ. 70, 149?159 (1992).

    CAS  PubMed  PubMed Central  Google Scholar 

  9. Dolin, P. J., Raviglione, M. C. & Kochi, A. Global tuberculosis incidence and mortality during 1990?2000. Bull. World Health Organ. 72, 213?220 (1994).

    CAS  PubMed  PubMed Central  Google Scholar 

  10. Hopewell, P. et al. Evaluation of new anti-infective drugs for the treatment and prevention of infections caused by the Mycobacterium avium complex. Infectious Diseases Society of America and the Food and Drug Administration. Clin. Infect. Dis. 15 (Suppl. 1), 296?306 (1992).

    Google Scholar 

  11. Smith, P. G. & Moss, A. R. In Tuberculosis: Pathogenesis, Protection, and Control. (ed Bloom, B. R.) 47?59 (American Society for Microbiology, Washington DC, 1994).

    Google Scholar 

  12. Kaufmann, S. H. & McMichael, A. J. Annulling a dangerous liaison: vaccination strategies against AIDS and tuberculosis. Nature Med. 11 (Suppl. 4), 33?44 (2005).

    Google Scholar 

  13. Lewinsohn, D. M., Lewinsohn, D. A. & Grotzke, J. E. TB vaccines at the turn of the century: insights into immunity to M. tuberculosis and modern approaches for prevention of an ancient disease. Semin. Respir. Infect. 18, 320?338 (2003).

    PubMed  Google Scholar 

  14. Flynn, J. L. & Chan, J. Immunology of tuberculosis. Annu. Rev. Immunol. 19, 93?129 (2001).

    CAS  PubMed  Google Scholar 

  15. Jouanguy, E. et al. Interferon- γ-receptor deficiency in an infant with fatal bacille Calmette-Guérin infection. N. Engl. J. Med. 335, 1956?1961 (1996).

    CAS  PubMed  Google Scholar 

  16. Jouanguy, E. et al. A human IFNGR1 small deletion hotspot associated with dominant susceptibility to mycobacterial infection. Nature Genet. 21, 370?378 (1999).

    CAS  PubMed  Google Scholar 

  17. Toussirot, E. & Wendling, D. The use of TNF-α blocking agents in rheumatoid arthritis: an overview. Expert Opin. Pharmacother. 5, 581?594 (2004).

    CAS  PubMed  Google Scholar 

  18. Havlir, D. V. & Barnes, P. F. Tuberculosis in patients with human immunodeficiency virus infection. N. Engl. J. Med. 340, 367?373 (1999).

    CAS  PubMed  Google Scholar 

  19. Cooper, A. M. et al. Disseminated tuberculosis in IFN-γ gene-disrupted mice. J. Exp. Med. 178, 2243?2247 (1993).

    CAS  PubMed  Google Scholar 

  20. Flynn, J. L. et al. An essential role for IFN-γ in resistance to Mycobacterium tuberculosis infection. J. Exp. Med. 178, 2249?2254 (1993).

    CAS  PubMed  Google Scholar 

  21. Flynn, J. L. et al. Major histocompatibility complex class I-restricted T cells are required for resistance to Mycobacterium tuberculosis infection. Proc. Natl Acad. Sci. USA 89, 12013?12017 (1992).

    CAS  PubMed  Google Scholar 

  22. Derrick, S. C. et al. Immunization with a DNA vaccine cocktail protects mice lacking CD4 cells against an aerogenic infection with Mycobacterium tuberculosis. Infect. Immun. 72, 1685?1692 (2004).

    CAS  PubMed  PubMed Central  Google Scholar 

  23. van Pinxteren, L. A. et al. Control of latent Mycobacterium tuberculosis infection is dependent on CD8 T cells. Eur. J. Immunol. 30, 3689?3698 (2000).

    CAS  PubMed  Google Scholar 

  24. Gonzalez-Juarrero, M. et al. Temporal and spatial arrangement of lymphocytes within lung granulomas induced by aerosol infection with Mycobacterium tuberculosis. Infect. Immun. 69, 1722?1728 (2001).

    CAS  PubMed  PubMed Central  Google Scholar 

  25. Ulrichs, T. et al. Human tuberculous granulomas induce peripheral lymphoid follicle-like structures to orchestrate local host defence in the lung. J. Pathol. 204, 217?228 (2004).

    PubMed  Google Scholar 

  26. Teitelbaum, R. et al. A mAb recognizing a surface antigen of Mycobacterium tuberculosis enhances host survival. Proc. Natl Acad. Sci. USA 95, 15688?15693 (1998).

    CAS  PubMed  Google Scholar 

  27. Sadoff, J. Public private partnership approach to vaccine development. Presented at New Approaches to Vaccine Development. (Sept. 8?10, Berlin, Germany, 2005).

  28. Bouneaud, C. et al. Lineage relationships, homeostasis, and recall capacities of central- and effector-memory CD8 T cells in vivo. J. Exp. Med. 201, 579?590 (2005).

    CAS  PubMed  PubMed Central  Google Scholar 

  29. Seder, R. A. & Ahmed, R. Similarities and differences in CD4+ and CD8+ effector and memory T cell generation. Nature Immunol. 4, 835?842 (2003).

    CAS  Google Scholar 

  30. Brewer, T. F. & Colditz, G. A. Relationship between bacille Calmette-Guérin (BCG) strains and the efficacy of BCG vaccine in the prevention of tuberculosis. Clin. Infect. Dis. 20, 126?135 (1995).

    CAS  PubMed  Google Scholar 

  31. Colditz, G. A. et al. Efficacy of BCG vaccine in the prevention of tuberculosis. Meta-analysis of the published literature. JAMA 271, 698?702 (1994).

    CAS  PubMed  Google Scholar 

  32. Fine, P. E. M., Carneiro, I. A. M., Milstien, J. B. & Clements, C. J. Issues relating to the use of BCG in immunization programmes (World Health Organization, Geneva, 1999).

  33. Colditz, G. A. et al. The efficacy of bacillus Calmette-Guérin vaccination of newborns and infants in the prevention of tuberculosis: meta-analyses of the published literature. Pediatrics 96, 29?35 (1995).

    CAS  PubMed  Google Scholar 

  34. Sterne, J. A., Rodrigues, L. C. & Guedes, I. N. Does the efficacy of BCG decline with time since vaccination? Int. J. Tuberc. Lung Dis. 2, 200?207 (1998).

    CAS  PubMed  Google Scholar 

  35. Aronson, N. E. et al. Long-term efficacy of BCG vaccine in American Indians and Alaska Natives: A 60-year follow-up study. JAMA 291, 2086?2091 (2004).

    CAS  PubMed  Google Scholar 

  36. Fine, P. E. The BCG story: lessons from the past and implications for the future. Rev. Infect. Dis. 11 (Suppl. 2), 353?359 (1989).

    Google Scholar 

  37. Comstock, G. W. Field trials of tuberculosis vaccines: how could we have done them better? Control Clin. Trials 15, 247?276 (1994).

    CAS  PubMed  Google Scholar 

  38. Soysal, A. et al. Effect of BCG vaccination on risk of Mycobacterium tuberculosis infection in children with household tuberculosis contact: a prospective community-based study. Lancet 366, 1443?1451 (2005).

    PubMed  Google Scholar 

  39. Tuberculosis Research Centre (ICMR), Chennai. Fifteen year follow up of trial of BCG vaccines in south India for tuberculosis prevention. Indian J. Med. Res. 110, 56?69 (1999).

  40. Horwitz, M. A. & Harth, G. A new vaccine against tuberculosis affords greater survival after challenge than the current vaccine in the guinea pig model of pulmonary tuberculosis. Infect. Immun. 71, 1672?1679 (2003).

    CAS  PubMed  PubMed Central  Google Scholar 

  41. Horwitz, M. A. et al. Recombinant bacillus Calmette-Guérin (BCG) vaccines expressing the Mycobacterium tuberculosis 30-kDa major secretory protein induce greater protective immunity against tuberculosis than conventional BCG vaccines in a highly susceptible animal model. Proc. Natl Acad. Sci. USA 97, 13853?13858 (2000).

    CAS  PubMed  Google Scholar 

  42. Hoft, D. F. Results of the 1st Phase I trial of a recombinant BCG TB vaccine (rBCG30). Presented at US?Japan Cooperative Medical Science Program; 40th Tuberculosis and Leprosy Research Conference. (Seattle, Washington, 2005).

  43. Hess, J. et al. Mycobacterium bovis bacille Calmette-Guérin strains secreting listeriolysin of Listeria monocytogenes. Proc. Natl Acad. Sci. USA 95, 5299?5304 (1998).

    CAS  PubMed  Google Scholar 

  44. Albert, M. L., Sauter, B. & Bhardwaj, N. Dendritic cells acquire antigen from apoptotic cells and induce class I-restricted CTLs. Nature 392, 86?89 (1998).

    CAS  PubMed  Google Scholar 

  45. Nasser Eddine, A. & Kaufmann, S. H. E. Improved protection by recombinant BCG. Microbes Infect. 7, 939?946 (2005).

    PubMed  Google Scholar 

  46. Grode, L. et al. Increased vaccine efficacy against tuberculosis of recombinant Mycobacterium bovis bacille Calmette-Guérin mutants that secrete listeriolysin. J. Clin. Invest. 115, 2472?2479 (2005).

    CAS  PubMed  PubMed Central  Google Scholar 

  47. Kaufmann, S. H. E. Rational vaccine design against tuberculosis. Presented at New Approaches to Vaccine Development. (Sept. 8?10, Berlin, Germany, 2005).

  48. Laufer, A. Managing the transition from academic vaccine research to license oriented development. Presented at New Approaches to Vaccine Development. (Sept. 8?10, Berlin, Germany, 2005).

  49. Portnoy, D. A. et al. Capacity of listeriolysin O, streptolysin O, and perfringolysin O to mediate growth of Bacillus subtilis within mammalian cells. Infect. Immun. 60, 2710?2717 (1992).

    CAS  PubMed  PubMed Central  Google Scholar 

  50. Edwards, K. M. et al. Iron-cofactored superoxide dismutase inhibits host responses to Mycobacterium tuberculosis. Am. J. Respir. Crit. Care Med. 164, 2213?2219 (2001).

    CAS  PubMed  Google Scholar 

  51. Kernodle, D. S. Pro-apoptotic BCG vaccine that enhances cellular immune responses and reduces tissue damage. Aeras Global TB Vaccine Foundation Scott Thaler Lecture Series. (Bethesda, Maryland, 2004).

  52. Jacobs, B. Live attenuated vaccines for TB: Mining the immune evasion function of the tubercle bacillus. Presented at New Approaches to Vaccine Development. (Sept. 8?10, Berlin, Germany, 2005).

  53. Chattergoon, M. A. et al. Targeted antigen delivery to antigen-presenting cells including dendritic cells by engineered Fas-mediated apoptosis. Nature Biotechnol. 18, 974?979 (2000).

    CAS  Google Scholar 

  54. Sheridan, J. P. et al. Control of TRAIL-induced apoptosis by a family of signaling and decoy receptors. Science 277, 818?821 (1997).

    CAS  PubMed  Google Scholar 

  55. Brosch, R. et al. Comparative genomics of the mycobacteria. Int. J. Med. Microbiol. 290, 143?152 (2000).

    CAS  PubMed  Google Scholar 

  56. Mahairas, G. G. et al. Molecular analysis of genetic differences between Mycobacterium bovis BCG and virulent M. bovis. J. Bacteriol. 178, 1274?1282 (1996).

    CAS  PubMed  PubMed Central  Google Scholar 

  57. Pym, A. S. et al. Recombinant BCG exporting ESAT-6 confers enhanced protection against tuberculosis. Nature Med. 9, 533?539 (2003).

    CAS  PubMed  Google Scholar 

  58. Pym, A. S. et al. Loss of RD1 contributed to the attenuation of the live tuberculosis vaccines Mycobacterium bovis BCG and Mycobacterium microti. Mol. Microbiol. 46, 709?717 (2002).

    CAS  PubMed  Google Scholar 

  59. Behr, M. A. et al. Comparative genomics of BCG vaccines by whole-genome DNA microarray. Science 284, 1520?1523 (1999).

    CAS  PubMed  Google Scholar 

  60. Gordon, S. V. et al. Identification of variable regions in the genomes of tubercle bacilli using bacterial artificial chromosome arrays. Mol. Microbiol. 32, 643?645 (1999).

    CAS  PubMed  Google Scholar 

  61. Salamon, H. et al. Detection of deleted genomic DNA using a semiautomated computational analysis of GeneChip data. Genome Res. 10, 2044?2054 (2000).

    CAS  PubMed  PubMed Central  Google Scholar 

  62. Kamath, A. T. et al. In New Live Mycobacterial Vaccines: Defining Essential Steps Towards Clinical Development. (WHO, Geneva, Switzerland, 2004).

    Google Scholar 

  63. Soto, C. Y. et al. IS6110 mediates increased transcription of the phoP virulence gene in a multidrug-resistant clinical isolate responsible for tuberculosis outbreaks. J. Clin. Microbiol. 42, 212?219 (2004).

    CAS  PubMed  PubMed Central  Google Scholar 

  64. Perez, E. et al. An essential role for phoP in Mycobacterium tuberculosis virulence. Mol. Microbiol. 41, 179?187 (2001).

    CAS  PubMed  Google Scholar 

  65. Guleria, I. et al. Auxotrophic vaccines for tuberculosis. Nature Med. 2, 334?337 (1996).

    CAS  PubMed  Google Scholar 

  66. Smith, D. A. et al. Characterization of auxotrophic mutants of Mycobacterium tuberculosis and their potential as vaccine candidates. Infect. Immun. 69, 1142?1150 (2001).

    CAS  PubMed  PubMed Central  Google Scholar 

  67. Jackson, M. et al. Persistence and protective efficacy of a Mycobacterium tuberculosis auxotroph vaccine. Infect. Immun. 67, 2867?2873 (1999).

    CAS  PubMed  PubMed Central  Google Scholar 

  68. Sambandamurthy, V. K. et al. Long-term protection against tuberculosis following vaccination with a severely attenuated double lysine and pantothenate auxotroph of Mycobacterium tuberculosis. Infect. Immun. 73, 1196?1203 (2005).

    CAS  PubMed  PubMed Central  Google Scholar 

  69. Sambandamurthy, V. K. et al. A pantothenate auxotroph of Mycobacterium tuberculosis is highly attenuated and protects mice against tuberculosis. Nature Med. 8, 1171?1174 (2002).

    CAS  PubMed  Google Scholar 

  70. Sambandamurthy, V. K. & Jacobs, W. R. Live attenuated mutants of Mycobacterium tuberculosis as candidate vaccines against tuberculosis. Microbes Infect. 7, 955?961 (2005).

    CAS  PubMed  Google Scholar 

  71. Andersen, A. B. & Hansen, E. B. Structure and mapping of antigenic domains of protein antigen b, a 38,000-molecular-weight protein of Mycobacterium tuberculosis. Infect. Immun. 57, 2481?2488 (1989).

    CAS  PubMed  PubMed Central  Google Scholar 

  72. Nagai, S. et al. Isolation and partial characterization of major protein antigens in the culture fluid of Mycobacterium tuberculosis. Infect. Immun. 59, 372?382 (1991).

    CAS  PubMed  PubMed Central  Google Scholar 

  73. Young, D. B. & Garbe, T. R. Lipoprotein antigens of Mycobacterium tuberculosis. Res. Microbiol. 142, 55?65 (1991).

    CAS  PubMed  Google Scholar 

  74. Andersen, P. et al. Recall of long-lived immunity to Mycobacterium tuberculosis infection in mice. J. Immunol. 154, 3359?3372 (1995).

    CAS  PubMed  Google Scholar 

  75. Skjot, R. L. et al. Comparative evaluation of low-molecular-mass proteins from Mycobacterium tuberculosis identifies members of the ESAT-6 family as immunodominant T-cell antigens. Infect. Immun. 68, 214?220 (2000).

    CAS  PubMed  PubMed Central  Google Scholar 

  76. Alderson, M. R. et al. Expression cloning of an immunodominant family of Mycobacterium tuberculosis antigens using human CD4+ T cells. J. Exp. Med. 191, 551?560 (2000).

    CAS  PubMed  PubMed Central  Google Scholar 

  77. Dillon, D. C. et al. Molecular and immunological characterization of Mycobacterium tuberculosis CFP-10, an immunodiagnostic antigen missing in Mycobacterium bovis BCG. J. Clin. Microbiol. 38, 3285?3290 (2000).

    CAS  PubMed  PubMed Central  Google Scholar 

  78. Skeiky, Y. A. et al. T-cell expression cloning of a Mycobacterium tuberculosis gene encoding a protective antigen associated with the early control of infection. J. Immunol. 165, 7140?7149 (2000).

    CAS  PubMed  Google Scholar 

  79. Laal, S. & Skeiky, Y. A. W. In Tuberculosis and the Tubercle Bacillus. (eds Cole, S. T. et al.) 71?83 (American Society for Microbiology Press, Washington DC, 2005).

    Google Scholar 

  80. Skeiky, Y. A. et al. Cloning, expression, and immunological evaluation of two putative secreted serine protease antigens of Mycobacterium tuberculosis. Infect. Immun. 67, 3998?4007 (1999).

    CAS  PubMed  PubMed Central  Google Scholar 

  81. Dillon, D. C. et al. Molecular characterization and human T-cell responses to a member of a novel Mycobacterium tuberculosis mtb39 gene family. Infect. Immun. 67, 2941?2950 (1999).

    CAS  PubMed  PubMed Central  Google Scholar 

  82. Covert, B. A. et al. The application of proteomics in defining the T-cell antigens of Mycobacterium tuberculosis. Proteomics 1, 574?586 (2001).

    CAS  PubMed  Google Scholar 

  83. Mattow, J. et al. Comparative proteome analysis of culture supernatant proteins from virulent Mycobacterium tuberculosis H37Rv and attenuated M. bovis BCG Copenhagen. Electrophoresis 24, 3405?3420 (2003).

    CAS  PubMed  Google Scholar 

  84. Mollenkopf, H. J. et al. Application of mycobacterial proteomics to vaccine design: improved protection by Mycobacterium bovis BCG prime?Rv3407 DNA boost vaccination against tuberculosis. Infect. Immun. 72, 6471?6479 (2004).

    CAS  PubMed  PubMed Central  Google Scholar 

  85. Huygen, K. et al. Immunogenicity and protective efficacy of a tuberculosis DNA vaccine. Nature Med. 2, 893?898 (1996).

    CAS  PubMed  Google Scholar 

  86. Baldwin, S. L. et al. Evaluation of new vaccines in the mouse and guinea pig model of tuberculosis. Infect. Immun. 66, 2951?2959 (1998).

    CAS  PubMed  PubMed Central  Google Scholar 

  87. Skjot, R. L. et al. Epitope mapping of the immunodominant antigen TB10.4 and the two homologous proteins TB10.3 and TB12.9, which constitute a subfamily of the esat-6 gene family. Infect. Immun. 70, 5446?5453 (2002).

    CAS  PubMed  PubMed Central  Google Scholar 

  88. Skeiky, Y. A. et al. Differential immune responses and protective efficacy induced by components of a tuberculosis polyprotein vaccine, Mtb72F, delivered as naked DNA or recombinant protein. J. Immunol. 172, 7618?7628 (2004).

    CAS  PubMed  Google Scholar 

  89. Weinrich Olsen, A. et al. Protection of mice with a tuberculosis subunit vaccine based on a fusion protein of antigen 85b and ESAT-6. Infect. Immun. 69, 2773?2778 (2001).

    CAS  PubMed  Google Scholar 

  90. Brandt, L. et al. The protective effect of the Mycobacterium bovis BCG vaccine is increased by coadministration with the Mycobacterium tuberculosis 72-kilodalton fusion polyprotein Mtb72F in M. tuberculosis-infected guinea pigs. Infect. Immun. 72, 6622?6632 (2004).

    CAS  PubMed  PubMed Central  Google Scholar 

  91. Olsen, A. W. et al. Efficient protection against Mycobacterium tuberculosis by vaccination with a single subdominant epitope from the ESAT-6 antigen. Eur. J. Immunol. 30, 1724?1732 (2000).

    CAS  PubMed  Google Scholar 

  92. Olsen, A. W. et al. Protective effect of a tuberculosis subunit vaccine based on a fusion of antigen 85B and ESAT-6 in the aerosol guinea pig model. Infect. Immun. 72, 6148?6150 (2004).

    CAS  PubMed  PubMed Central  Google Scholar 

  93. Mazurek, G. H. et al. Comparison of a whole-blood IFN-γ assay with tuberculin skin testing for detecting latent Mycobacterium tuberculosis infection. JAMA 286, 1740?1747 (2001).

    CAS  PubMed  Google Scholar 

  94. Mazurek, G. H. & Villarino, M. E. Guidelines for using the QuantiFERON-TB test for diagnosing latent Mycobacterium tuberculosis infection. Centers for Disease Control and Prevention. MMWR Recomm. Rep. 52, 15?18 (2003).

    PubMed  Google Scholar 

  95. Dietrich, J. et al. Exchanging ESAT-6 with TB10. 4 in an Ag85B fusion molecule-based tuberculosis subunit vaccine: efficient protection and ESAT-6-based sensitive monitoring of vaccine efficacy. J. Immunol. 174, 6332?6339 (2005).

    CAS  PubMed  Google Scholar 

  96. Brooks, J. V. et al. Boosting vaccine for tuberculosis. Infect. Immun. 69, 2714?2717 (2001).

    CAS  PubMed  PubMed Central  Google Scholar 

  97. Goonetilleke, N. P. et al. Enhanced immunogenicity and protective efficacy against Mycobacterium tuberculosis of bacille Calmette-Guérin vaccine using mucosal administration and boosting with a recombinant modified vaccinia virus Ankara. J. Immunol. 171, 1602?1609 (2003).

    CAS  PubMed  Google Scholar 

  98. Wang, J. et al. Single mucosal, but not parenteral, immunization with recombinant adenoviral-based vaccine provides potent protection from pulmonary tuberculosis. J. Immunol. 173, 6357?6365 (2004).

    CAS  PubMed  Google Scholar 

  99. Vogels, R. et al. Replication-deficient human adenovirus type 35 vectors for gene transfer and vaccination: efficient human cell infection and bypass of pre-existing adenovirus immunity. J. Virol. 77, 8263?8271 (2003).

    CAS  PubMed  PubMed Central  Google Scholar 

  100. Havenga et al. Novel replication-incompetent adenoviral B-group vectors. J. Virol. (In the press).

  101. Hone, D. Optimization of nucleic acid vaccine delivery by bacterial vectors. Presented at New Approaches to Vaccine Development. (Sept. 8?10, Berlin, Germany, 2005).

  102. Schnappinger, D. et al. Transcriptional adaptation of Mycobacterium tuberculosis within macrophages: insights into the phagosomal environment. J. Exp. Med. 198, 693?704 (2003).

    CAS  PubMed  PubMed Central  Google Scholar 

  103. Voskuil, M. I. et al. Inhibition of respiration by nitric oxide induces a Mycobacterium tuberculosis dormancy program. J. Exp. Med. 198, 705?713 (2003).

    CAS  PubMed  PubMed Central  Google Scholar 

  104. Capuano, S. V. et al. Experimental Mycobacterium tuberculosis infection of cynomolgus macaques closely resembles the various manifestations of human M. tuberculosis infection. Infect. Immun. 71, 5831?5844 (2003).

    CAS  PubMed  PubMed Central  Google Scholar 

  105. Hussey, G., Hawkridge, T., Geiter, L. & Hanekom, W. Presented at TB vaccines for the world (April 19?21, Vienna, Austria, 2006).

  106. McShane, H. et al. Recombinant MVA85A boosts BCG-primed and naturally acquired antimycobacterial immunity in humans. Nature Med. 10, 1240?1244 (2004).

    CAS  PubMed  Google Scholar 

  107. Radosevic, K. et al. Presented at TB vaccines for the world (April 19?21, Vienna, Austria, 2006).

    Google Scholar 

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Acknowledgements

We are grateful to Dr. L. Barker for his input and critical reading of this article. The Aeras Global TB Vaccine Foundation is supported by a major grant from the Bill and Melinda Gates Foundation.

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  1. Aeras Global TB Vaccine Foundation, 1405 Research Blvd, Rockville, 20850, Maryland, USA

    Yasir A. W. Skeiky & Jerald C. Sadoff

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Skeiky, Y., Sadoff, J. Advances in tuberculosis vaccine strategies. Nat Rev Microbiol 4, 469–476 (2006). https://doi.org/10.1038/nrmicro1419

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