The BCG Experience: Implications for Future Vaccines against Tuberculosis

Abstract

Use of BCG (bacille Calmette-Guerin) vaccines increased in Europe after World War II and in developing countries starting in the 1950s to the extent that the vaccines have now been given to over 3 billion people. In a major evaluation of BCG's safety, researchers attempted to catalog all adverse events reported as attributed to BCG vaccination. Two conclusions are notable. First, the reports of severe neurologic or fatal sequelae indicate that the risk of such events is extremely rare, far less than that reported for the smallpox vaccine. Second, BCG vaccines are associated with a variety of more common minor adverse effects in addition to induration and ulceration of the vaccination site, which occur in almost all vaccines. The authors believe that such studies may identify useful surrogate markers for the evaluation of different preparations of BCG or new vaccines against tuberculosis. Although BCG is effective in developing type I CD4 T-cell responses, it is still unclear how effective it is in generating MHC class I-restricted CTL responses. It may ultimately be necessary to identify the molecules, either enzymes or lysins, that enable M. tuberculosis to escape from phagolysosomes into the cytoplasm in order to develop recombinant BCG vaccines that are effective in inducing both CD8- and CD4-type protective responses. Just as the BCG trials have provided our most detailed studies of the epidemiology of tuberculosis, so basic research directed at tuberculosis vaccines is leading the way in understanding pathogenesis of the disease.