Each year, 10 million people contract tuberculosis and 2 million die as a result of the disease. An estimated 2 billion individuals – a third of the world's population – have been exposed to Myobacterium tuberculosis (MTB) and carry the infection in its latent form, retaining a lifelong risk of developing TB disease.  To stop the spread of tuberculosis, scientists are working to develop methods that prevent new infections and also eliminate infection in the huge reservoir of people who already are infected with MTB. New approaches that focus on controlling or stimulating the immune system to cure latent infections or prevent MTB from causing disease have the potential to significantly reduce illness, death, and disease transmission.

Dr. Andersen’s is leading a collaborative team of international researchers who are studying Myobacterium tuberculosis to identify the mechanisms that, in some people, allow it to escape natural immune system responses. The project's ultimate goal is to develop vaccines that target latent TB, either before or after an individual is infected.

The project strategy is based on the hypothesis that current vaccines fail to combat latent infection because gene expression by the bacterium changes in response to host immune mechanisms. This results in a slow- or non-replicating stage of infection that has a markedly different antigen repertoire than acute disease. Dr. Andersen and his colleagues are working to identify these "late genes" and to use their corresponding antigens as a basis for post-exposure vaccines or in combination with conventional "early" vaccine antigens. This latter approach would allow a single vaccine regimen to be used to reduce both acute and reactivation tuberculosis disease.

The Andersen team will continue to evaluate novel rBCG strains that have been or are being developed. They plan to expand the number of candidate vaccines potentially active against latent infection in the animal model to increase the size of the pool from which to select the most promising candidates. In their work on developing a multistage vaccine, they plan to transition from proof-of-concept experiments demonstrating activity of selected antigens after exposure to developing and testing the efficacy of a new prototype multistage vaccine.