title: An adjunctive therapeutic vaccine against reactivation and post-treatment relapse tuberculosis.
abstract: Preventing latently infected or inadequately treated individuals from progressing to active disease could make a major impact on tuberculosis (TB) control worldwide. The purpose of this study was to evaluate a new approach to prevent reactivation and TB relapse that combines drug treatment and vaccination. Mycobacterium tuberculosis harbors a gene called mce1R that, in vivo, negatively regulates a 13-gene cluster called the mce1 operon. In a Cornell mouse model, BALB/c mice infected with M. tuberculosis H37Rv disrupted in mce1R consistently develop latent infection and reactivation disease. We used this new mouse model to test a recombinant M. tuberculosis cell wall protein (Mce1A), encoded by a gene in the mce1 operon, for its ability to prevent post-treatment TB. At 32 weeks of follow-up, a complete sterilizing protection was observed in lungs of the vaccinated mice. Mce1A but not phosphate-buffered saline administered intraperitoneally during the period of latent infection prevented disease progression and proliferation of M. tuberculosis mce1R mutant. The only visible lung lesions in vaccinated mice included small clusters of lymphocytes, while the unvaccinated mice showed progressively enlarging granulomas comprised of foamy macrophages surrounded by lymphocytes. The combination of anti-TB drugs and a vaccine may serve as a powerful treatment modality against TB reactivation and relapse.
authors.affiliation: Division of Infectious Diseases and Vaccinology, 201 Hildebrand Hall, School of Public Health, University of California, Berkeley, CA 94720, USA.
authors.forename: Toshiko
authors.initials: T
authors.lastname: Miyata
authors.forename: Chan-Ick
authors.initials: CI
authors.lastname: Cheigh
authors.forename: Nicola
authors.initials: N
authors.lastname: Casali
authors.forename: Amador
authors.initials: A
authors.lastname: Goodridge
authors.forename: Olivera
authors.initials: O
authors.lastname: Marjanovic
authors.forename: Lon V
authors.initials: LV
authors.lastname: Kendall
authors.forename: Lee W
authors.initials: LW
authors.lastname: Riley
mesh_terms: D000818:Animals; D000995:Antitubercular Agents / Q000008:administration & dosage*; D058491:Bacterial Load; D001426:Bacterial Proteins / Q000235:genetics; D004195:Disease Models, Animal; D005260:Female; D006099:Granuloma / Q000473:pathology; D008168:Lung / Q000276:immunology / Q000382:microbiology / Q000473:pathology; D008214:Lymphocytes / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D009169:Mycobacterium tuberculosis / Q000276:immunology* / Q000302:isolation & purification / Q000472:pathogenicity; D055502:Secondary Prevention; D014376:Tuberculosis / Q000188:drug therapy* / Q000276:immunology* / Q000382:microbiology / Q000473:pathology; D032581:Tuberculosis Vaccines / Q000008:administration & dosage*
chemical_list: D000995:Antitubercular Agents; D001426:Bacterial Proteins; D032581:Tuberculosis Vaccines; C473802:mammalian cell entry protein Mce1A, Mycobacterium tuberculosis
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