title: Bactericidal activity in whole blood as a potential surrogate marker of immunity after vaccination against tuberculosis.
abstract: The development of new tuberculosis (TB) vaccines will require the identification of correlates of human protection. This study examined the balance between immunity and virulence in a whole blood infection model in which intracellular mycobacterial survival was measured using BACTEC. In the blood of tuberculin-negative donors, counts of Mycobacterium tuberculosis H(37)Ra organisms fell by 0.14 log(10) CFU during 96 h of whole blood culture, whereas counts of Mycobacterium bovis BCG, M. tuberculosis H(37)Rv, and a clinical TB isolate's organisms increased by 0.13, 0.43, and 1.04 log(10) CFU, respectively (P < 0.001), consistent with their relative virulence. Inhibition of tumor necrosis factor alpha by the addition of methylprednisolone or pentoxifylline or removal of CD4(+) or CD8(+) T cells by magnetic beads had deleterious effects on immune control of intracellular growth only in the blood of tuberculin-positive donors. Repeated vaccination of eight tuberculin-negative volunteers with M. bovis BCG resulted in a 0.3 log (50%) reduction in BCG CFU counts in the model compared to baseline values (P < 0.05). Three of the volunteers responded only after the second vaccination. These experiments indicate that whole blood culture may be used to measure immunity to M. tuberculosis and that further studies of repeated BCG vaccination are warranted.
authors.affiliation: Case Western Reserve University, Cleveland, Ohio, USA.
authors.forename: Seon-Hee
authors.initials: SH
authors.lastname: Cheon
authors.forename: Beate
authors.initials: B
authors.lastname: Kampmann
authors.forename: Amy G
authors.initials: AG
authors.lastname: Hise
authors.forename: Manijeh
authors.initials: M
authors.lastname: Phillips
authors.forename: Ho-Yeon
authors.initials: HY
authors.lastname: Song
authors.forename: Katherine
authors.initials: K
authors.lastname: Landen
authors.forename: Qing
authors.initials: Q
authors.lastname: Li
authors.forename: Rhonda
authors.initials: R
authors.lastname: Larkin
authors.forename: Jerrold J
authors.initials: JJ
authors.lastname: Ellner
authors.forename: Richard F
authors.initials: RF
authors.lastname: Silver
authors.forename: Daniel F
authors.initials: DF
authors.lastname: Hoft
authors.forename: Robert S
authors.initials: RS
authors.lastname: Wallis
mesh_terms: D000328:Adult; D015415:Biomarkers / Q000097:blood; D001769:Blood / Q000382:microbiology*; D015169:Colony Count, Microbial; D016207:Cytokines / Q000097:blood; D006801:Humans; D007109:Immunity; D008722:Methods; D009163:Mycobacterium bovis / Q000254:growth & development / Q000472:pathogenicity; D009169:Mycobacterium tuberculosis / Q000254:growth & development / Q000472:pathogenicity; D016176:T-Lymphocyte Subsets / Q000276:immunology; D014376:Tuberculosis / Q000382:microbiology / Q000628:therapy*; D014611:Vaccination / Q000592:standards
chemical_list: D015415:Biomarkers; D016207:Cytokines