Investigation of the relationships between immune-mediated inhibition of mycobacterial growth and other potential surrogate markers of protective Mycobacterium tuberculosis immunity

Daniel F. Hoft, Shewangizaw Worku, Beate Kampmann, Christopher C. Whalen, Jerrold J. Ellner, Christina S. Hirsch, Robin B. Brown, Rhonda Larkin, Qing Li, Hyun Yun, Richard F. Silver

Research output: Contribution to journalArticle

Abstract

Tuberculosis (TB) vaccine development is hindered by the lack of clear surrogate markers of protective human immunity to Mycobacterium tuberculosis. This study evaluated the hypothesis that immune-mediated inhibition of mycobacterial growth would more directly correlate with protective TB immunity than other immunologic responses. Bacille Calmette-Guérin (BCG) vaccination, known to induce partial protection against TB, was used as a model system to investigate mechanistic relationships among different parameters of antigen-specific immunity. Effects of primary and booster intradermal BCG vaccinations were assessed in 3 distinct assays of mycobacterial inhibition. Correlations between vaccine-induced growth inhibition and other immune responses were analyzed. BCG significantly enhanced all antigen-specific responses. Peak responses occurred at 2 months after boosting. Statistical analyses suggested that each assay measured unique aspects of mycobacterial immunity. Despite previous evidence that type 1 immune responses are essential for TB immunity, interferon-γ production did not correlate with mycobacterial inhibition. These results have important implications for TB vaccine development.

Original languageEnglish (US)
Pages (from-to)1448-1457
Number of pages10
JournalJournal of Infectious Diseases
Volume186
Issue number10
DOIs
StatePublished - Nov 15 2002
Externally publishedYes

ASJC Scopus subject areas

  • Public Health, Environmental and Occupational Health
  • Immunology

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    Hoft, D. F., Worku, S., Kampmann, B., Whalen, C. C., Ellner, J. J., Hirsch, C. S., Brown, R. B., Larkin, R., Li, Q., Yun, H., & Silver, R. F. (2002). Investigation of the relationships between immune-mediated inhibition of mycobacterial growth and other potential surrogate markers of protective Mycobacterium tuberculosis immunity. Journal of Infectious Diseases, 186(10), 1448-1457. https://doi.org/10.1086/344359