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Case Western Reserve University Tuberculosis Research Unit
  Integrating research to combat the global TB epidemic
 
 

Predictors of Immune Response and Progression to TB Disease in Infants Vaccinated at Birth with BCG


Type of Study

Prospective observational study

Design

Case control study

Project Site

Western Cape, South Africa

Sample Size

total 12,700 subjects
Infants were assigned to 1 of 3 groups:

Population

Objective 1: BCG vaccinated newborns and adolescents

Objective 2: 33 BCG vaccinated newborns per time point (3, 6, 10, 14, 27 and 40 weeks)

Objective 3: 11,680 BCG vaccinated newborns, followed to identify children with active TB (cases) and exposed children who did not develop disease (controls)

Objective 4: 900 BCG vaccinated newborns, followed to identify 300 children with active TB (cases) and 600 exposed children who did not develop disease (controls)

Objective 5: All pediatric Mtb isolates from site over past 2 years

Study Period

2008-2012

Goal of Study:

We aim to identify immune correlates of vaccination-induced resistance to subsequent TB disease.

Objectives of Study:
  1. Validate newly identified vaccination-induced immune correlate(s) of protection against TB disease, following vaccination of newborns with BCG.
  2. Determine the longitudinal kinetics of the immune response to BCG, in infants vaccinated at birth.
    1. Determine the kinetics of BCG induced T cell responses over the first year of life.
    2. Determine when to boost BCG-specific immunity.
    3. Characterize BCG-specific T cell functional capacity, effector mechanisms and memory subsets over the first year of life.
  3. Determine whether innate immune gene polymorphisms are associated with differences in ex vivo measured immune responses to BCG, in infants vaccinated at birth.
  4. Determine whether innate immune gene polymorphisms are associated with lack of BCG-induced protection against TB, in infants vaccinated at birth.
  5. Determine whether infection with certain Mtb strains is preferentially associated with TB disease in BCG-vaccinated neonates not protected against disease by the vaccine.
Research Activities: