Bactericidal activity in whole blood as a potential surrogate marker of immunity after vaccination against tuberculosis

Seon Hee Cheon, Beate Kampmann, Amy G. Hise, Manijeh Phillips, Ho Yeon Song, Katherine Landen, Qing Li, Rhonda Larkin, Jerrold J. Ellner, Richard F. Silver, Daniel F. Hoft, Robert S. Wallis

Research output: Contribution to journalArticlepeer-review

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 H37Ra organisms fell by 0.14 log14 CFU during 96 h of whole blood culture, whereas counts of Mycobacterium bovis BCG, M. tuberculosis H37Rv, and a clinical TB isolate's organisms increased by 0.13, 0.43, and 1.04 log10 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.

Original languageEnglish (US)
Pages (from-to)901-907
Number of pages7
JournalClinical and Diagnostic Laboratory Immunology
Volume9
Issue number4
DOIs
StatePublished - 2002
Externally publishedYes

ASJC Scopus subject areas

  • Clinical Biochemistry
  • Immunology
  • Immunology and Allergy
  • Microbiology (medical)

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