title: Assessment of the genetic diversity of Mycobacterium tuberculosis esxA, esxH, and fbpB genes among clinical isolates and its implication for the future immunization by new tuberculosis subunit vaccines Ag85B-ESAT-6 and Ag85B-TB10.4.
abstract: The effort to develop a tuberculosis (TB) vaccine more effective than the widely used Bacille Calmette-Guérin (BCG) has led to the development of two novel fusion protein subunit vaccines: Ag85B-ESAT-6 and Ag85B-TB10.4. Studies of these vaccines in animal models have revealed their ability to generate protective immune responses. Yet, previous work on TB fusion subunit vaccine candidate, Mtb72f, has suggested that genetic diversity among M. tuberculosis strains may compromise vaccine efficacy. In this study, we sequenced the esxA, esxH, and fbpB genes of M. tuberculosis encoding ESAT-6, TB10.4, and Ag85B proteins, respectively, in a sample of 88 clinical isolates representing 57 strains from Ark, USA, and 31 strains from Turkey, to assess the genetic diversity of the two vaccine candidates. We found no DNA polymorphism in esxA and esxH genes in the study sample and only one synonymous single nucleotide change (C to A) in fbpB gene among 39 (44.3%) of the 88 strains sequenced. These data suggest that it is unlikely that the efficacy of Ag85B-ESAT-6 and Ag85B-TB10.4 vaccines will be affected by the genetic diversity of M. tuberculosis population. Future studies should include a broader pool of M. tuberculosis strains to validate the current conclusion.
authors.affiliation: Department of Epidemiology, School of Public Health, University of Michigan, Ann Arbor, MI 48109-2029, USA.
authors.forename: Jose
authors.initials: J
authors.lastname: Davila
authors.forename: Lixin
authors.initials: L
authors.lastname: Zhang
authors.forename: Carl F
authors.initials: CF
authors.lastname: Marrs
authors.forename: Riza
authors.initials: R
authors.lastname: Durmaz
authors.forename: Zhenhua
authors.initials: Z
authors.lastname: Yang
mesh_terms: D000217:Acyltransferases / Q000235:genetics*; D000942:Antigens, Bacterial / Q000235:genetics*; D001426:Bacterial Proteins / Q000235:genetics*; D005798:Genes, Bacterial / Q000235:genetics*; D014644:Genetic Variation; D006801:Humans; D009169:Mycobacterium tuberculosis / Q000235:genetics* / Q000302:isolation & purification; D014376:Tuberculosis / Q000382:microbiology; D032581:Tuberculosis Vaccines / Q000235:genetics*; D022223:Vaccines, Subunit / Q000235:genetics
chemical_list: D000942:Antigens, Bacterial; D001426:Bacterial Proteins; C093276:ESAT-6 protein, Mycobacterium tuberculosis; C501710:TB10.4 antigen, Mycobacterium tuberculosis; D032581:Tuberculosis Vaccines; D022223:Vaccines, Subunit; D000217:Acyltransferases; C121433:antigen 85B, Mycobacterium tuberculosis