Isoniazid - BCG - DMID 07-0083

Phase I Study of Whether Preclearance of Latent M. tuberculosis (MTB) Infection with Isoniazid (INH) Enhances Specific Immune Response to MTB Following Subsequent BCG Revaccination in Healthy, HIV-uninfected, Tuberculin Skin Test Positive Adults


DMID Protocol Number: 07-0083

Type of Study

Phase 1 Clinical Trial


Randomized, Parallel Arm, Open-Label Phase 1 Clinical Trial

Project Site

South African Tuberculosis Vaccine Initiative (SATVI), Worcester, South Africa

Sample Size

82 subjects


Healthy, HIV-uninfected, TST+ adults 18-40 years old with prior BCG vaccination in infancy

Study Period


Goal of Study:

Current TB vaccination strategies have little protective efficacy against the development of pulmonary TB in adults - the main source of TB transmission in the community. Earlier studies also have shown little benefit from revaccination with current BCG vaccines. TST positive adults with latent TB infection represent the largest group (an estimated one-third of the world\x92s population or 2 billion persons) at risk for TB. Recent data suggest that preclearance (treatment of LTBI) with isoniazid (INH), which decreases or eliminates latent tubercle bacilli, may result in enhanced MTB specific immune responses. This trial will test the hypothesis that the effect of preclearance of latent MTB infection with INH treatment will enhance immune responses to BCG revaccination.

Objectives of Study:

Primary Objectives:

  1. Determine the effect of INH preclearance on the kinetics and characteristics of the specific immune response following BCG revaccination in adults with latent M. tuberculosis (MTB) infection (TST positive).
  2. Determine the safety and reactogenicity of BCG revaccination in TST+ adults.

Secondary Objectives:

  1. Determine the effect of INH preclearance and BCG revaccination on MTB-specific Th1 effector and central memory cell function.
  2. Determine the effect of INH preclearance and BCG revaccination on MTB-specific Treg cell function.
  3. Determine the effect of INH preclearance and BCG revaccination on innate immune responses as measured by T cell mediated inhibition of intracellular mycobacterial growth and inflammatory cytokine production.
  4. Determine whether a host gene expression signature can predict immunological outcome of BCG vaccination.


Published Papers:

Hatherill M, Geldenhuys H, Pienaar B, Suliman S, Chheng P, Debanne SM, Hoft DF, Boom WH Hanekom WA, Johnson JL.  Safety and reactogenicity of BCG revaccinatyion with isoniazid pretreatment in TST positive adults. Vaccine. 2014; 32:3982-3988. PMCID: PMC4135306.

Suliman S, Geldenhuys H, Johnson JL, Hughes JE, Smit E, Murphy M, Toefy A, Lerumo L, Hopley C, Pienaar B, Chheng P, Nemes E, Hoft DF, Hanekom WA, Boom WH,  Hatherill M, Scriba TJ.  Bacillus Calmette-Guerin (BCG) revaccination of adults with latent Mycobacterium tuberculosis infection induces long-lived BCG-reactive NK cell responses.  J Immunol. 2016; 197:1100-1110. PMCID: PMC4976036/