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The Promise of New TB Vaccines

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Handbook of Global Tuberculosis Control

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Abstract

The development of new, safe, and effective tuberculosis (TB) vaccines to prevent TB across all age groups and countries in an affordable and sustainable manner is critical for the eventual control of TB worldwide. Several new TB vaccines are currently being investigated in human clinical trials, mostly in Africa, including new live recombinant, protein-adjuvanted subunit, and virally vectored products. Since it is unclear at this time whether they will be effective, research on new types of TB vaccines containing novel antigens and unique modes of delivery continues to be important, as does research on the immunological basis of the disease. Likewise, a better understanding of the various manifestations of the disease, including latent infection, remains a critical goal for making better vaccines. Clinical studies of new vaccines and new delivery approaches in emerging countries throughout the world will be required in order to identify vaccines that will have a meaningful impact on global TB.

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References

  • Aagaard, C., Hoang, T., Dietrich, J., Cardona, P. J., Izzo, A., Dolganov, G., et al. (2011). A multistage tuberculosis vaccine that confers efficient protection before and after exposure. Nature Medicine, 17(2), 189–194. doi:10.1038/nm.2285.

    Article  CAS  PubMed  Google Scholar 

  • Abel, B., Tameris, M., Mansoor, N., Gelderbloem, S., Hughes, J., Abrahams, D., et al. (2010). The novel tuberculosis vaccine, AERAS-402, induces robust and polyfunctional CD4+ and CD8+ T cells in adults. American Journal of Respiratory and Critical Care Medicine, 181(12), 1407–1417.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Aronson, J. D., Aronson, C. F., & Taylor, H. C. (1958). A twenty-year appraisal of BCG vaccination in the control of tuberculosis. AMA Archives of Internal Medicine, 101(5), 881–893.

    Article  CAS  PubMed  Google Scholar 

  • Baldwin, S. L., D’Souza, C., Roberts, A. D., Kelly, B. P., Frank, A. A., Lui, M. A., et al. (1998). Evaluation of new vaccines in the mouse and guinea pig model of tuberculosis. Infection and Immunity, 66(6), 2951–2959.

    CAS  PubMed  PubMed Central  Google Scholar 

  • Barker, L. F., Brennan, M. J., Rosenstein, P. K., & Sadoff, J. C. (2009). Tuberculosis vaccine research: The impact of immunology. Current Opinion in Immunology, 21(3), 331–338. doi:10.1016/j.coi.2009.05.017.

    Article  CAS  PubMed  Google Scholar 

  • Barker, L. F., Leadman, A. E., & Clagett, B. (2011). The challenges of developing new tuberculosis vaccines. Health Affairs, 30(6), 1073–1079. doi:10.1377/hlthaff.2011.0303.

    Article  PubMed  Google Scholar 

  • Bartley, J. (2010). Vitamin D, innate immunity and upper respiratory tract infection. Journal of Laryngology and Otology, 124(5), 465–469. doi:10.1017/s0022215109992684.

    Article  CAS  PubMed  Google Scholar 

  • Behar, S. M., Martin, C. J., Nunes-Alves, C., Divangahi, M., & Remold, H. G. (2011). Lipids, apoptosis, and cross-presentation: Links in the chain of host defense against Mycobacterium tuberculosis. Microbes and Infection, 13(8–9), 749–756. doi:10.1016/j.micinf.2011.03.002.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Behr, M. A. (2002). BCG—Different strains, different vaccines? The Lancet Infectious Diseases, 2(2), 86–92.

    Article  PubMed  Google Scholar 

  • Behr, M. A., & Small, P. M. (1999). A historical and molecular phylogeny of BCG strains. Vaccine, 17(7–8), 915–922.

    Article  CAS  PubMed  Google Scholar 

  • Berry, M. P., Graham, C. M., McNab, F. W., Xu, Z., Bloch, S. A., Oni, T., et al. (2010). An interferon-inducible neutrophil-driven blood transcriptional signature in human tuberculosis. Nature, 466(7309), 973–977. doi:10.1038/nature09247.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Bertholet, S., Ireton, G. C., Kahn, M., Guderian, J., Mohamath, R., Stride, N., et al. (2008). Identification of human T cell antigens for the development of vaccines against Mycobacterium tuberculosis. Journal of Immunology, 181(11), 7948–7957.

    Article  CAS  Google Scholar 

  • Bertholet, S., Ireton, G. C., Ordway, D. J., Windish, H. P., Pine, S. O., Kahn, M., et al. (2010). A defined tuberculosis vaccine candidate boosts BCG and protects against multidrug-resistant Mycobacterium tuberculosis. Science Translational Medicine, 2(53), 53ra74. doi:10.1126/scitranslmed.3001094.

    Article  PubMed  PubMed Central  Google Scholar 

  • Beverley, P., Ronan, E., Lee, L., Arnold, I., Bolinger, B., Powrie, F., et al. (2013). Environmental effects on protection against Mycobacterium tuberculosis after immunization with Ad85A. Vaccine, 31(7), 1086–1093. doi:10.1016/j.vaccine.2012.12.024.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Bosio, C. M., Gardner, D., & Elkins, K. L. (2000). Infection of B cell-deficient mice with CDC 1551, a clinical isolate of Mycobacterium tuberculosis: Delay in dissemination and development of lung pathology. Journal of Immunology, 164(12), 6417–6425.

    Article  CAS  Google Scholar 

  • Brennan, M. J., & Thole, J. (2012). Tuberculosis vaccines: A strategic blueprint for the next decade. Tuberculosis (Edinburgh, Scotland), 92(Suppl 1), S6–S13. doi:10.1016/S1472-9792(12)70005-7.

    Article  Google Scholar 

  • Calmette, A. (1931). Preventive vaccination against tuberculosis with BCG. Proceedings of the Royal Society of Medicine, 24(11), 1481–1490.

    CAS  PubMed  PubMed Central  Google Scholar 

  • Chambers, M. A., Williams, A., Gavier-Widen, D., Whelan, A., Hughes, C., Hall, G., et al. (2001). A guinea pig model of low-dose Mycobacterium bovis aerogenic infection. Veterinary Microbiology, 80(3), 213–226.

    Article  CAS  PubMed  Google Scholar 

  • Chen, C. Y., Huang, D., Wang, R. C., Shen, L., Zeng, G., Yao, S., et al. (2009). A critical role for CD8 T cells in a nonhuman primate model of tuberculosis. PLoS Pathogens, 5(4), e1000392. doi:10.1371/journal.ppat.1000392.

    Article  PubMed  PubMed Central  Google Scholar 

  • Colditz, G. A., Brewer, T. F., Berkey, C. S., Wilson, M. E., Burdick, E., Fineberg, H. V., et al. (1994). Efficacy of BCG vaccine in the prevention of tuberculosis. Meta-analysis of the published literature. JAMA, 271(9), 698–702.

    Article  CAS  PubMed  Google Scholar 

  • Colditz, G. A., Berkey, C. S., Mosteller, F., Brewer, T. F., Wilson, M. E., Burdick, E., et al. (1995). The efficacy of bacillus Calmette-Guerin vaccination of newborns and infants in the prevention of tuberculosis: Meta-analyses of the published literature. Pediatrics, 96(1 Pt 1), 29–35.

    CAS  PubMed  Google Scholar 

  • Comas, I., Chakravartti, J., Small, P. M., Galagan, J., Niemann, S., Kremer, K., et al. (2010). Human T cell epitopes of Mycobacterium tuberculosis are evolutionarily hyperconserved. Nature Genetics, 42(6), 498–503. doi:10.1038/ng.590.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Corbel, M. J., Fruth, U., Griffiths, E., & Knezevic, I. (2004). Report on a WHO consultation on the characterisation of BCG strains, Imperial College, London 15–16 December 2003. Vaccine, 22(21–22), 2675–2680.

    Article  CAS  PubMed  Google Scholar 

  • Datta, M., Vallishayee, R. S., & Diwakara, A. M. (1999). Fifteen year follow up of trial of BCG vaccines in south India for tuberculosis prevention. Indian Journal of Medical Research, 110, 56–69.

    Google Scholar 

  • Dietrich, J., Aagaard, C., Leah, R., Olsen, A. W., Stryhn, A., Doherty, T. M., et al. (2005). Exchanging ESAT6 with TB10.4 in an Ag85B fusion molecule-based tuberculosis subunit vaccine: Efficient protection and ESAT6-based sensitive monitoring of vaccine efficacy. Journal of Immunology, 174(10), 6332–6339.

    Article  CAS  Google Scholar 

  • Fourth Report of Medical Research Council. (1972). BCG and vole bacillus vaccines in the prevention of tuberculosis in adolescence and early adult life. Bulletin of the World Health Organization, 46(3), 371–385.

    Google Scholar 

  • Gagneux, S., & Brennan, M. J. (2010). Strain and antigenic variation in Mycobacterium tuberculosis: Implications for the development of new tools for tuberculosis. The Art and Science of Tuberculosis Vaccine Development, 1, 129–146.

    Google Scholar 

  • Glatman-Freedman, A., & Casadevall, A. (1998). Serum therapy for tuberculosis revisited: Reappraisal of the role of antibody-mediated immunity against Mycobacterium tuberculosis. Clinical Microbiology Reviews, 11(3), 514–532.

    CAS  PubMed  PubMed Central  Google Scholar 

  • Grode, L., Seiler, P., Baumann, S., Hess, J., Brinkmann, V., Nasser Eddine, A., et al. (2005). Increased vaccine efficacy against tuberculosis of recombinant Mycobacterium bovis bacille Calmette-Guerin mutants that secrete listeriolysin. Journal of Clinical Investigation, 115(9), 2472–2479. doi:10.1172/JCI24617.

  • Hawkridge, T., Scriba, T. J., Gelderbloem, S., Smit, E., Tameris, M., Moyo, S., et al. (2008). Safety and immunogenicity of a new tuberculosis vaccine, MVA85A, in healthy adults in South Africa. Journal of Infectious Diseases, 198(4), 544–552. doi:10.1086/590185.

    Article  PubMed  PubMed Central  Google Scholar 

  • Hesseling, A. C., & Gie, R. P. (2007). Scoring systems for the diagnosis of childhood tuberculosis: Are we making progress? The International Journal of Tuberculosis and Lung Disease, 11(3), 245.

    PubMed  Google Scholar 

  • Hoft, D. F., Brown, R. M., & Belshe, R. B. (2000). Mucosal bacille calmette-Guerin vaccination of humans inhibits delayed-type hypersensitivity to purified protein derivative but induces mycobacteria-specific interferon-gamma responses. Clinical Infectious Diseases, 30(Suppl 3), S217–S222. doi:10.1086/313864.

    Article  CAS  PubMed  Google Scholar 

  • Kaufmann, S. H. (2010). Future vaccination strategies against tuberculosis: Thinking outside the box. Immunity, 33(4), 567–577. doi:10.1016/j.immuni.2010.09.015.

    Article  CAS  PubMed  Google Scholar 

  • Layre, E., Paepe, D. C., Larrouy-Maumus, G., Vaubourgeix, J., Mundayoor, S., Lindner, B., et al. (2011). Deciphering sulfoglycolipids of Mycobacterium tuberculosis. Journal of Lipid Research, 52(6), 1098–1110. doi:10.1194/jlr.M013482.

  • Leroux-Roels, I., Leroux-Roels, G., Ofori-Anyinam, O., Moris, P., De Kock, E., Clement, F., et al. (2010). Evaluation of the safety and immunogenicity of two antigen concentrations of the Mtb72F/AS02(A) candidate tuberculosis vaccine in purified protein derivative-negative adults. Clinical and Vaccine Immunology, 17(11), 1763–1771. doi:10.1128/CVI.00133-10.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Li, Z., Zhang, H., Fan, X., Zhang, Y., Huang, J., Liu, Q., et al. (2006). DNA electroporation prime and protein boost strategy enhances humoral immunity of tuberculosis DNA vaccines in mice and non-human primates. Vaccine, 24(21), 4565–4568. doi:10.1016/j.vaccine.2005.08.021.

    Article  CAS  PubMed  Google Scholar 

  • Lotte, A., Wasz-Hockert, O., Poisson, N., Engbaek, H., Landmann, H., Quast, U., et al. (1988). Second IUATLD study on complications induced by intradermal BCG-vaccination. Bulletin of the International Union against Tuberculosis and Lung Disease, 63(2), 47–59.

    CAS  PubMed  Google Scholar 

  • Ma, F.-B., Xu, W.-G., Chen, Y., Lu, J.-Z., Xiao-Zhu, D., Wang, Y.-L., et al. (2011). Observation of effect and safety on Mycobacterium vaccae for prevention of pulmonary tuberculosis. Chinese Journal of Antituberculosis, 33(10), 637–640.

    Google Scholar 

  • McMurray, D. N. (2001). Disease model: Pulmonary tuberculosis. Trends in Molecular Medicine, 7(3), 135–137.

    Article  CAS  PubMed  Google Scholar 

  • McShane, H., & Hill, A. (2005). Prime-boost immunisation strategies for tuberculosis. Microbes and Infection, 7(5–6), 962–967. doi:10.1016/j.micinf.2005.03.009.

    Article  CAS  PubMed  Google Scholar 

  • Pulendran, B., Li, S., & Nakaya, H. I. (2010). Systems vaccinology. Immunity, 33(4), 516–529. doi:10.1016/j.immuni.2010.10.006.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Ramsay, A., Steingart, K. R., & Pai, M. (2010). Assessing the impact of new diagnostics on tuberculosis control. The International Journal of Tuberculosis and Lung Disease, 14(12), 1506–1507.

    PubMed  Google Scholar 

  • Rodrigues, L. C., Diwan, V. K., & Wheeler, J. G. (1993). Protective effect of BCG against tuberculous meningitis and miliary tuberculosis: A meta-analysis. International Journal of Epidemiology, 22(6), 1154–1158.

    Article  CAS  PubMed  Google Scholar 

  • Stukova, M. A., Sereinig, S., Zabolotnyh, N. V., Ferko, B., Kittel, C., Romanova, J., et al. (2006). Vaccine potential of influenza vectors expressing Mycobacterium tuberculosis ESAT-6 protein. Tuberculosis (Edinburgh, Scotland), 86(3–4), 236–246. doi:10.1016/j.tube.2006.01.010.

  • Tameris, M. D., Hatherill, M., Landry, B. S., Scriba, T. J., Snowden, M. A., Lockhart, S., et al. (2013). Safety and efficacy of MVA85A, a new tuberculosis vaccine, in infants previously vaccinated with BCG: A randomised, placebo-controlled phase 2b trial. Lancet, 381(9871), 1021–1028. doi:10.1016/S0140-6736(13)60177-4.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • van Dissel, J. T., Arend, S. M., Prins, C., Bang, P., Tingskov, P. N., Lingnau, K., et al. (2010). Ag85B-ESAT-6 adjuvanted with IC31 promotes strong and long-lived Mycobacterium tuberculosis specific T cell responses in naive human volunteers. Vaccine, 28(20), 3571–3581. doi:10.1016/j.vaccine.2010.02.094.

  • Verreck, F. A., Vervenne, R. A., Kondova, I., van Kralingen, K. W., Remarque, E. J., Braskamp, G., et al. (2009). MVA.85A boosting of BCG and an attenuated, phoP deficient M. tuberculosis vaccine both show protective efficacy against tuberculosis in rhesus macaques. PLoS One, 4(4), e5264. doi:10.1371/journal.pone.0005264.

    Article  PubMed  PubMed Central  Google Scholar 

  • Vilaplana, C., Montane, E., Pinto, S., Barriocanal, A. M., Domenech, G., Torres, F., et al. (2010). Double-blind, randomized, placebo-controlled Phase I Clinical Trial of the therapeutical antituberculous vaccine RUTI (R). Vaccine, 28(4), 1106–1116. doi:10.1016/j.vaccine.2009.09.134.

    Article  CAS  PubMed  Google Scholar 

  • von Reyn, C. F., Mtei, L., Arbeit, R. D., Waddell, R., Cole, B., Mackenzie, T., et al. (2010). Prevention of tuberculosis in Bacille Calmette-Guerin-primed, HIV-infected adults boosted with an inactivated whole-cell mycobacterial vaccine. AIDS, 24(5), 675–685. doi:10.1097/QAD.0b013e3283350f1b.

    Article  Google Scholar 

  • Wells, W. A., Konduri, N., Chen, C., Lee, D., Ignatius, H. R., Gardiner, E., et al. (2010). Tuberculosis regimen change in high-burden countries. The International Journal of Tuberculosis and Lung Disease, 14(12), 1538–1547.

    CAS  PubMed  Google Scholar 

  • Xing, Z., McFarland, C. T., Sallenave, J. M., Izzo, A., Wang, J., & McMurray, D. N. (2009). Intranasal mucosal boosting with an adenovirus-vectored vaccine markedly enhances the protection of BCG-primed guinea pigs against pulmonary tuberculosis. PLoS One, 4(6), e5856. doi:10.1371/journal.pone.0005856.

    Article  PubMed  PubMed Central  Google Scholar 

  • Zvi, A., Ariel, N., Fulkerson, J., Sadoff, J. C., & Shafferman, A. (2008). Whole genome identification of Mycobacterium tuberculosis vaccine candidates by comprehensive data mining and bioinformatic analyses. BMC Medical Genomics, 1, 18. doi:10.1186/1755-8794-1-18.

  • Zwerling, A., Behr, M. A., Verma, A., Brewer, T. F., Menzies, D., & Pai, M. (2011). The BCG world atlas: A database of global BCG vaccination policies and practices. PLoS Medicine, 8(3), e1001012.

    Article  PubMed  PubMed Central  Google Scholar 

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Acknowledgments

We thank Jennifer Woolley, Daniel Yeboah-Kordieh, and Bartholt Clagett of Aeras for their contributions to the figure presented in this chapter.

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Authors and Affiliations

  1. Aeras, Rockville, MD, 20850, USA

    Michael J. Brennan Ph.D., Lewellys F. Barker M.D., M.P.H. & Thomas Evans M.D.

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  1. Michael J. Brennan Ph.D.
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  2. Lewellys F. Barker M.D., M.P.H.
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  3. Thomas Evans M.D.
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Correspondence to Michael J. Brennan Ph.D. .

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Editors and Affiliations

  1. Haikou VTI Biological Institute, Boston, Massachusetts, USA

    Yichen Lu

  2. Chinese Nat’l Ctr Disease Control and Prevention, Nat’l Center for TB Control & Prevention Chinese Nat’l Ctr Disease Control and Prevention, Beijing, China

    Lixia Wang

  3. National Center for Tuberculosis Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing, China

    Hongjin Duanmu

  4. Brookline, Massachusetts, USA

    Chris Chanyasulkit

  5. Vaccine Technologies, Inc., Wellesley, Massachusetts, USA

    Amie J. Strong

  6. National Center for Tuberculosis Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing, China

    Hui Zhang

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Brennan, M.J., Barker, L.F., Evans, T. (2017). The Promise of New TB Vaccines. In: Lu, Y., Wang, L., Duanmu, H., Chanyasulkit, C., Strong, A., Zhang, H. (eds) Handbook of Global Tuberculosis Control. Springer, Boston, MA. https://doi.org/10.1007/978-1-4939-6667-7_27

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