Tuberculosis (TB) kills 1.5 million people worldwide each year. Incomplete understanding of protective host immunity against TB is hampering development of novel, effective vaccines to control this epidemic.
As a first step in vaccine development, Dr. Hanekom's group aims to describe immune correlates of protection induced by the only current vaccine, Mycobacterium bovis BCG. The researchers have already collected, processed and stored blood from 5,675 10-week old South African infants, routinely vaccinated with BCG at birth. Infants who subsequently develop TB, following exposure to adults with the disease, will be identified—these infants will not have been protected by the vaccine. A control group of infants protected by the vaccine will also be identified: infants who have remained healthy despite exposure. The investigators will retrieve blood, stored from 10 weeks of age, of protected and unprotected infants, and compare immunity in the 2 groups.
Dr. Hanekom's group will examine immune responses conventionally associated with protection against mycobacteria, and look for novel immune correlates of protection with DNA micro-array technology. However, based on their preliminary data and on recent evidence that regulatory CD4+CD25+ T cells (TRegs) critically determine the outcome of intracellular infections, they will also investigate regulation of this immunity. Their hypothesis is that BCG vaccination of newborns results in a spectrum of functional TReg induction. It is proposed that the magnitude of this response correlates inversely with conventional BCG-specific immunity, and may ultimately be a "negative" correlate of vaccine efficacy.