ジョウキョウ ト イウ ガイネン ニ モトズク イミカン ジョウキョウ イミロン ショウカイ

Introduction: Mycobacterium tuberculosis kills more people than any other pathogen. Vaccination is the most cost-effective control measure for any infectious disease. Development of an effective vaccine against tuberculosis is hindered by the uncertain predictive value of preclinical animal models, incomplete understanding of protective immunity and lack of validated immune correlates of protection (COP). Areas covered: Here we review what is known about protective immunity against M.tb, the preclinical and clinical cohorts that can be utilized to identify COP, and COP that have been identified to date. Expert commentary: The identification of COP would allow the rational design and development of vaccine candidates which can then be optimized and prioritized based on the induction of these immune responses. Once validated in field efficacy trials, such COP could potentially facilitate the development and licensure of vaccines, in combination with human efficacy data. The identification and validation of COP would represent a very significant advance in TB vaccine development. Every opportunity to collect samples and cohorts on which to cross-validate pre-existing COP and identify novel COP should be exploited. Furthermore, global cooperation and collaboration on such samples will ensure that the utility of such precious samples is fully exploited

A polymorphism in human MR1 is associated with mRNA expression and susceptibility to tuberculosis

The MR1 antigen-presenting system is conserved among mammals and enables T cells to recognize small molecules produced by bacterial pathogens, including Mycobacterium tuberculosis (M.tb). However, it is not known if MR1-mediated antigen presentation is important for protective immunity against mycobacterial disease. We hypothesized that genetic control of MR1 expression correlates with clinical outcomes of tuberculosis infection. We performed an MR1 candidate gene association study and identified an intronic SNP (rs1052632) that was significantly associated with susceptibility to tuberculosis in a discovery and validation cohort of Vietnamese adults with tuberculosis. Stratification by site of disease revealed that rs1052632 genotype GG was strongly associated with the development of meningeal tuberculosis (OR=2.99; 95%CI 1.64-5.43; p=0.00006). Among patients with meningeal disease, absence of the G allele was associated with an increased risk of death (HR=3.86; 95%CI 1.49-9.98; p=0.005). Variant annotation tools using public databases indicate that rs1052632 is strongly associated with MR1 gene expression in lymphoblastoid cells (p=0.004) and is located within a transcriptional enhancer in epithelial keratinocytes. These data support a role for MR1 in the pathogenesis of human tuberculosis by revealing that rs1052632 is associated with MR1 gene expression and susceptibility to tuberculosis in Vietnam