Learning from BCG: Designing a better tuberculosis vaccine.

Abstract Extract: Prior to the advent of vaccination, disease caused by M. tuberculosis had two age-related peaks: one in the first few 2-3 years of life characterized by a very high incidence of mortality and a later peak in adult life starting in the late teens or early twenties. Today, where most of the global population is vaccinated with BCG, TB mainly manifests as a pulmonary disease in the adult population. The first clinical studies with Mycobacterium bovis bacille Calmette-Guerin (BCG) -- an attenuated pathogen and still the only vaccine available -- started in 1921 and demonstrated that BCG was highly efficient in protecting against TB in children. After the Second World War, the vaccine was offered to children throughout Europe, and today WHO recommends that infants should be immunized as soon after birth as possible with a single, intradermal dose of BCG in all countries at high risk of TB infection. To date, more than 3 billion people have received BCG, which makes BCG one of the most widely used vaccines in the world. The current consensus is that neonatal vaccination with BCG protects children efficiently against the early (and often severe) manifestations of TB, such as TB meningitis, regardless of settings. In contrast, its efficacy against pulmonary disease in adults has varied from 0% to 80% in different studies.