Even though such responses can be mimicked by vaccination, mechanisms of protection induced by vaccination may differ from those induced after natural infection. Despite these challenges, a recent landmark POI trial tested the ability of BCG revaccination or H4:IC31 subunit vaccination to prevent M. tuberculosis infection in healthy South African adolescents (9). ESAT-6, PDIMs, and PGLs execute numerous immune evasion strategies in macrophages, including for phagosome rupture and cytosolic escape of M. tuberculosis and upregulation of responses detrimental to the host (for example, aberrant type I IFN levels) (126–128). Considering growing evidence of their role in immune evasion and virulence, these ESX systems are increasingly targeted for the development of live recombinant mycobacterial vaccines (119, 120), and the preferential recognition of ESX antigens by T cells following natural infection has made them attractive candidates for subunit vaccine development (121) (Fig. It follows that a fine balance between different immune cell subsets and their pro- and anti-inflammatory mediators is required to control M. tuberculosis (42). Chez les enfants nés de mère séropositive, la vaccination ne doit pas être pratiquée avant de s'être assuré de l'absence d'infection de l'enfant par le VIH.

H56 and an earlier version, comprising Ag85B and ESAT-6 (H1), were safe and immunogenic when combined with the IC31 or CAF01 adjuvant, as pre- or postexposure vaccines (183–186). The 54% vaccine efficacy reported in this trial establishes for the first time the proof of principle of vaccine-induced protection against clinical TB disease among persons already infected with M. tuberculosis. However, it is important to address whether resisters, who remain TST and IGRA negative and possess non-IFN-γ T-cell responses to M. tuberculosis-specific proteins (21), truly resist M. tuberculosis infection or whether they still harbor M. tuberculosis infection. Therefore, BCG strain heterogeneity may likely have implications for new BCG boosting or supplementation strategies. In the first efficacy trial carried out in BCG-vaccinated South African infants, boosting with MVA85A did not show significant improvement over BCG in preventing M. tuberculosis infection or TB disease (6) (Fig. 2) instead employs the strategy of attenuation by double deletions of the phoP and fadD26 virulence genes, which leads to the complete abolishment of PDIM biosynthesis and defects in the ESX-1 system. Cases resembling cancer associated retinopathy (CAR) without a serum reaction to the CAR autoantigen have been reported (Sharon et al 2005). This knowledge has facilitated the engineering of recombinant BCG (rBCG) candidates with cytosolic-escape capability that appear more immunogenic and safer in immunocompromised hosts (130). An additional phase 2a POD trial of TB/FLU-04L is currently planned for QFT-positive adults. Despite BCG vaccine limitations, the WHO continues to recommend that a single dose of BCG should be given to neonates or as soon as possible after birth in countries with a high prevalence of TB for protection against TB meningitis and miliary TB [54]. Candidates currently being tested for POR include the H56:IC31 and ID93:GLA-SE subunit vaccines, which were shown to prevent reactivation or limit disease severity in nonhuman primates (NHPs) (154, 155), as well as the rBCG vaccine candidate VPM1002 (see below). Access the complete reference list online at http://www.expertconsult.com, Anneke C Hesseling, Marcel A Behr, in Tuberculosis, 2009. With ∼1.6 million deaths annually, TB, an ancient airborne disease caused by Mycobacterium tuberculosis, is the top killer among all infectious diseases worldwide (1). Putative correlates could also be validated in resisters, who experience repeated, intense M. tuberculosis exposures (for example, in health care workers in high-incidence settings and in household contacts) but never convert their skin test or become IGRA positive (35). These breakthroughs, based on the greatly expanded knowledge of the M. tuberculosis infection spectrum, immunology of TB, and vaccine platforms, have reinvigorated the TB vaccine field. The left arm is recommended by the World Health Organization (WHO).

Il est composé de bacilles tuberculeux vivants, mais affaiblis. 1). H1 is no longer in the clinical pipeline. One common feature of all BCG strains is the absence of 6-kDa early secretory antigenic target (ESAT-6) secretion system 1 (ESX-1), owing to the deletion of region of difference 1 (RD1) (118).

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