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