Chapter 10 : Clinical Testing of Tuberculosis Vaccine Candidates

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The need for a new tuberculosis (TB) vaccination strategy is clear when we consider the massive burden of TB disease in countries where universal infant bacille Calmette-Guérin (BCG) vaccination is practiced as part of the World Health Organization (WHO) Expanded Program on Immunization (EPI) ( ). The lifetime risk for development of TB disease in these high-transmission settings is driven by multiple ongoing exposure-re-exposure episodes, beginning in early childhood, leading to infection at an early age, and continuing throughout adulthood ( Fig. 1 ). Infants and very young children not only have a higher risk of progression from infection to disease, but have a higher risk of severe disease, including miliary TB and tuberculous meningitis ( ). Since BCG vaccine is thought to offer protective efficacy of about 74% against all forms of TB disease in children, BCG vaccination is firmly entrenched in the EPI ( ). However, although BCG vaccination is thought to offer modest protection against infection as defined by interferon-gamma (IFN-γ) release assay (IGRA) conversion, the majority of adults in high-TB-burden countries are -infected ( ). In very high-transmission settings such as South Africa, more than three quarters of adolescents are -infected by the time they leave high school ( ). Given that the rate of infection in some African countries may exceed 10% per annum ( ), it is not surprising that while Africa is responsible for only 28% of the world’s new TB cases, 7 of the top 10 countries for TB incidence by population are in Africa, where HIV coinfection, a younger population demographic, and social disadvantage and disruption add susceptibility to TB disease ( ). It is against this backdrop that we review the potential indications for TB vaccines, in search of a vaccination strategy that is safe and effective against all forms of TB disease in infants, children, and adults, including -infected and HIV-infected people.

Citation: Hatherill M, Tait D, McShane H. 2017. Clinical Testing of Tuberculosis Vaccine Candidates, p 193-211. In Jacobs, Jr. W, McShane H, Mizrahi V, Orme I (ed), Tuberculosis and the Tubercle Bacillus, Second Edition. ASM Press, Washington, DC. doi: 10.1128/microbiolspec.TBTB2-0015-2016
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Figure 1

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

Citation: Hatherill M, Tait D, McShane H. 2017. Clinical Testing of Tuberculosis Vaccine Candidates, p 193-211. In Jacobs, Jr. W, McShane H, Mizrahi V, Orme I (ed), Tuberculosis and the Tubercle Bacillus, Second Edition. ASM Press, Washington, DC. doi: 10.1128/microbiolspec.TBTB2-0015-2016
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Figure 2

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

Citation: Hatherill M, Tait D, McShane H. 2017. Clinical Testing of Tuberculosis Vaccine Candidates, p 193-211. In Jacobs, Jr. W, McShane H, Mizrahi V, Orme I (ed), Tuberculosis and the Tubercle Bacillus, Second Edition. ASM Press, Washington, DC. doi: 10.1128/microbiolspec.TBTB2-0015-2016
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Figure 3

Prevention of TB disease (POD) vaccine strategy.

Citation: Hatherill M, Tait D, McShane H. 2017. Clinical Testing of Tuberculosis Vaccine Candidates, p 193-211. In Jacobs, Jr. W, McShane H, Mizrahi V, Orme I (ed), Tuberculosis and the Tubercle Bacillus, Second Edition. ASM Press, Washington, DC. doi: 10.1128/microbiolspec.TBTB2-0015-2016
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Figure 4

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

Citation: Hatherill M, Tait D, McShane H. 2017. Clinical Testing of Tuberculosis Vaccine Candidates, p 193-211. In Jacobs, Jr. W, McShane H, Mizrahi V, Orme I (ed), Tuberculosis and the Tubercle Bacillus, Second Edition. ASM Press, Washington, DC. doi: 10.1128/microbiolspec.TBTB2-0015-2016
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Figure 5

Current global clinical pipeline of TB vaccine candidates.

Citation: Hatherill M, Tait D, McShane H. 2017. Clinical Testing of Tuberculosis Vaccine Candidates, p 193-211. In Jacobs, Jr. W, McShane H, Mizrahi V, Orme I (ed), Tuberculosis and the Tubercle Bacillus, Second Edition. ASM Press, Washington, DC. doi: 10.1128/microbiolspec.TBTB2-0015-2016
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