Exploiting immunology and molecular genetics for rational vaccine design against tuberculosis.

One hundred years after the Nobel Prize was awarded to Robert Koch for his work on tuberculosis (TB) and 85 years after the development of the attenuated vaccine strain, Mycobacterium bovis bacille Calmette-Guérin (BCG), by Albert Calmette and Camille Guérin, effective prevention measures against TB are still not available. However, the first decade of the 21st century will witness the implementation of clinical trials with several novel vaccine candidates. These candidates fall into two groups: (1) subunit vaccines aimed at boosting the immune response induced by a BCG prime, and (2) recombinant (r)BCG improved to replace the current BCG vaccine strain. For boosting, protein and DNA vaccines in suitable adjuvant or delivery systems, respectively, as well as recombinant viral carriers, such as recombinant modified vaccinia virus Ankara, are being tested. For rBCG prime, a vaccine strain with higher immunogenicity and a strain overexpressing a dominant antigen have been developed. These vaccine candidates will have passed phase I clinical trials before the end of 2006. The goal for the future would be to have these novel vaccine candidates tested in different combinations to facilitate the design of the most efficacious vaccination protocol.