Chapter 45 : Immune Intervention Strategies against Tuberculosis

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Immune Intervention Strategies against Tuberculosis, Page 1 of 2

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Compared to most other infectious diseases, 10 million new cases of active tuberculosis (TB) annually is a horrifyingly high death rate. However, of the 2 billion individuals infected with , a mere 10% of infections transform into active TB disease. These comparisons also illustrate the effectiveness of naturally acquired immunity in containing , thus preventing TB disease outbreak. Immunity induced by chronic infection as well as immunity induced by vaccination, however, has to be long lived. Delayed type hypersensitivity (DTH) measures the encounter of the immune system with and hence cannot distinguish between latently infected individuals and patients with active TB disease. Novel vaccine strategies aim at either boosting bacille Calmette-Guérin (BCG) vaccine in children, boosting BCG later in adolescents, or replacing BCG with novel live vaccines such as genetically modified strains of BCG (rBCG), or attenuated strains of . DNA vaccines are easy to make and have the obvious advantage that they can be administered without the need for adjuvants. After injection, the DNA is introduced into host cells, which present the antigen in the context of MHC class I molecules, or they release the antigen, which is then engulfed, processed, and presented in the context of MHC class I by macrophages and DCs. Envisaging of highly speculative immune intervention strategies blocks PD ligand (PD-L)/programmed death 1 (PD-1) signaling, thus leading to T-cell exhaustion. This could prevent or at least delay outbreak of TB in latently infected individuals.

Citation: Andersen P, Kaufmann S. 2011. Immune Intervention Strategies against Tuberculosis, p 571-586. In Kaufmann S, Rouse B, Sacks D (ed), The Immune Response to Infection. ASM Press, Washington, DC. doi: 10.1128/9781555816872.ch45

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Vaccination strategies. A preventive vaccine (cvrrently BCG) is given at birth to prevent infection and clinical disease. Novel vaccine strategies aim at either boosting BCG in children (early booster), boosting BCG later in adolescents (late booster), or replacing BCG with novel live vaccines such as genetically modified strains of BCG (rBCG), or attenuated strains of The ultimate vaccine strategy may also be based on a combination of both approaches (i.e., a prime-boost vaccination regime composed of priming with the best possible viable vaccine candidate and boosting with the best possible subunit vaccine candidate). A postexposure booster is designed to be effective against latent infection and to prevent reactivation of TB.

Citation: Andersen P, Kaufmann S. 2011. Immune Intervention Strategies against Tuberculosis, p 571-586. In Kaufmann S, Rouse B, Sacks D (ed), The Immune Response to Infection. ASM Press, Washington, DC. doi: 10.1128/9781555816872.ch45
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Image of FIGURE 2

Different types of TB vaccination outcomes. The figure describes the course of disease in nonvaccinated individuals (solid line) and different forms of development that the disease may take. The dotted line depicts the outcome of vaccination, which delays TB outbreak. This is the lowest hurdle followed by consistent control of dormant to achieve lifelong latent infection, or, in other words, prevention of TB outbreak. A better option would be vaccines that achieve sterilizing immunity. An alternative would be vaccine-induced prevention of stable infection with (“vaccine prevents infection” line). The two latter options guarantee protection against TB even if an individual becomes infected with HIV, which causes disease outbreak in latently infected individuals.

Citation: Andersen P, Kaufmann S. 2011. Immune Intervention Strategies against Tuberculosis, p 571-586. In Kaufmann S, Rouse B, Sacks D (ed), The Immune Response to Infection. ASM Press, Washington, DC. doi: 10.1128/9781555816872.ch45
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Mycobacterial antigens in leading vaccine candidates

Citation: Andersen P, Kaufmann S. 2011. Immune Intervention Strategies against Tuberculosis, p 571-586. In Kaufmann S, Rouse B, Sacks D (ed), The Immune Response to Infection. ASM Press, Washington, DC. doi: 10.1128/9781555816872.ch45
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The leading TB vaccine candidates in clinical trials

Citation: Andersen P, Kaufmann S. 2011. Immune Intervention Strategies against Tuberculosis, p 571-586. In Kaufmann S, Rouse B, Sacks D (ed), The Immune Response to Infection. ASM Press, Washington, DC. doi: 10.1128/9781555816872.ch45

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