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Review
. 2012;8(5):e1002607.
doi: 10.1371/journal.ppat.1002607. Epub 2012 May 10.

Vaccines against tuberculosis: where are we and where do we need to go?

Tom H M Ottenhoff  1 , Stefan H E Kaufmann
Affiliations
Review

Vaccines against tuberculosis: where are we and where do we need to go?

Tom H M Ottenhoff et al. PLoS Pathog. 2012.

Abstract

In this review we discuss recent progress in the development, testing, and clinical evaluation of new vaccines against tuberculosis (TB). Over the last 20 years, tremendous progress has been made in TB vaccine research and development: from a pipeline virtually empty of new TB candidate vaccines in the early 1990s, to an era in which a dozen novel TB vaccine candidates have been and are being evaluated in human clinical trials. In addition, innovative approaches are being pursued to further improve existing vaccines, as well as discover new ones. Thus, there is good reason for optimism in the field of TB vaccines that it will be possible to develop better vaccines than BCG, which is still the only vaccine available against TB.

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Conflict of interest statement

I have read the journal's policy and have the following conflicts: TO is co-inventor of an Mtb latency antigen patent, which is owned by LUMC. SHEK is co-inventor of the rBCGΔUreC:Hly vaccine candidate and of the vaccine antigen Rv3407, and member of the Scientific Advisory Boards of Intercell, Vienna, and Vakzine Projekt Management (VPM), Hannover.

Figures

Figure 1
Figure 1. The three stages of tuberculosis.
Stage 1: Infection of Mycobacterium tuberculosis (Mtb) frequently occurs at a young age. Metabolically active Mtb are inhaled and subsequently T-cells are stimulated which carry the major burden of acquired immunity. These include major histocompatability complex class II (MHC II)-restricted CD4 T-cells and MHC I-restricted CD8 T-cells. B cells are also activated but their protective role in TB remains elusive. Pre-exposure vaccines are given at this early stage. Novel pre-exposure vaccine candidates are given very soon after birth and thus generally before infection with Mtb. They either substitute for Bacille Calmette Guérin (BCG) or boost immunity induced by BCG. Stage 2: Acquired immunity comprising CD4 and CD8 T-cells contains Mtb in a dormant stage within solid granulomas. T-cells produce type I cytokines and cytolytic effector molecules. They become memory T-cells which concomitantly produce multiple cytokines. Individuals remain latently infected without clinical signs of active tuberculosis (TB). Post-exposure vaccines are given to adolescents or adults who are latently infected but healthy. Stage 3: Mechanisms leading to deficient immunity and disease reactivation are numerous and include production of suppressive cytokines such as interleukin (IL)-10 and transforming growth factor-beta (TGFβ) by T helper 2 (Th2) cells and regulatory T(reg) cells as well as T-cell exhaustion mediated by inhibitory receptor-coreceptor interactions on antigen presenting cells (APCs) and T-cells. Mtb becomes metabolically active and granulomas become caseous. Mtb can be spread to other organs and to other individuals. Therapeutic vaccines are given to TB patients in adjunct to chemotherapy.
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