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Clinical Testing of Tuberculosis Vaccine Candidates

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  • Authors: Mark Hatherill1, Dereck Tait2, Helen McShane3
  • Editors: William R. Jacobs Jr.4, Helen McShane5, Valerie Mizrahi6, Ian M. Orme7
  • VIEW AFFILIATIONS HIDE AFFILIATIONS
    Affiliations: 1: South African Tuberculosis Vaccine Initiative (SATVI) and Institute of Infectious Disease and Molecular Medicine (IDM), University of Cape Town, Cape Town, South Africa 7925; 2: Aeras, Cape Town, South Africa 7925; 3: The Jenner Institute, University of Oxford, Oxford OX3 7DQ, United Kingdom; 4: Howard Hughes Medical Institute, Albert Einstein School of Medicine, Bronx, NY 10461; 5: University of Oxford, Oxford OX3 7DQ, United Kingdom; 6: University of Cape Town, Rondebosch 7701, South Africa; 7: Colorado State University, Fort Collins, CO 80523
  • Source: microbiolspec September 2016 vol. 4 no. 5 doi:10.1128/microbiolspec.TBTB2-0015-2016
  • Received 16 February 2015 Accepted 04 April 2016 Published 23 September 2016
  • H. McShane, helen.mcshane@ndm.ox.ac.uk
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  • Abstract:

    It is almost 100 years since the development of bacille Calmette-Guérin (BCG), the only licensed vaccine against tuberculosis (TB). While BCG does confer consistent protection against disseminated disease, there is an urgent need for a more effective vaccine against pulmonary disease. There are several indications for such an improved vaccine, including prevention of infection, prevention of disease, and a therapeutic vaccine to prevent recurrent disease. The two main approaches to TB vaccine development are developing an improved whole mycobacterial priming agent to replace BCG and/or developing a subunit booster vaccine to be administered after a BCG or BCG replacement priming vaccination. In this article we review the status of the current candidate vaccines being evaluated in clinical trials. The critical challenges to successful TB vaccine development are the uncertain predictive value of the preclinical animal models and the lack of a validated immune correlate of protection. While it is relatively simple to evaluate safety and immunogenicity in phase 1/2 studies, the evaluation of efficacy requires complex studies with large numbers of subjects and long periods of follow-up. This article reviews the potential role for human Experimental Medicine studies, in parallel with product development, to help improve the predictive value of the early-stage trials.

  • Citation: Hatherill M, Tait D, McShane H. 2016. Clinical Testing of Tuberculosis Vaccine Candidates. Microbiol Spectrum 4(5):TBTB2-0015-2016. doi:10.1128/microbiolspec.TBTB2-0015-2016.

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/content/journal/microbiolspec/10.1128/microbiolspec.TBTB2-0015-2016
2016-09-23
2017-04-28

Abstract:

It is almost 100 years since the development of bacille Calmette-Guérin (BCG), the only licensed vaccine against tuberculosis (TB). While BCG does confer consistent protection against disseminated disease, there is an urgent need for a more effective vaccine against pulmonary disease. There are several indications for such an improved vaccine, including prevention of infection, prevention of disease, and a therapeutic vaccine to prevent recurrent disease. The two main approaches to TB vaccine development are developing an improved whole mycobacterial priming agent to replace BCG and/or developing a subunit booster vaccine to be administered after a BCG or BCG replacement priming vaccination. In this article we review the status of the current candidate vaccines being evaluated in clinical trials. The critical challenges to successful TB vaccine development are the uncertain predictive value of the preclinical animal models and the lack of a validated immune correlate of protection. While it is relatively simple to evaluate safety and immunogenicity in phase 1/2 studies, the evaluation of efficacy requires complex studies with large numbers of subjects and long periods of follow-up. This article reviews the potential role for human Experimental Medicine studies, in parallel with product development, to help improve the predictive value of the early-stage trials.

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FIGURE 1

BCG vaccination, exposure, infection, and TB disease in a high-TB-burden setting.

Source: microbiolspec September 2016 vol. 4 no. 5 doi:10.1128/microbiolspec.TBTB2-0015-2016
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FIGURE 2

Prevention of (MTB) infection (POI) vaccine strategy.

Source: microbiolspec September 2016 vol. 4 no. 5 doi:10.1128/microbiolspec.TBTB2-0015-2016
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FIGURE 3

Prevention of TB disease (POD) vaccine strategy.

Source: microbiolspec September 2016 vol. 4 no. 5 doi:10.1128/microbiolspec.TBTB2-0015-2016
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FIGURE 4

Prevention of recurrence (POR) and therapeutic TB vaccine strategies.

Source: microbiolspec September 2016 vol. 4 no. 5 doi:10.1128/microbiolspec.TBTB2-0015-2016
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FIGURE 5

Current global clinical pipeline of TB vaccine candidates.

Source: microbiolspec September 2016 vol. 4 no. 5 doi:10.1128/microbiolspec.TBTB2-0015-2016
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