Tuberculosis (TB) remains a leading infectious disease worldwide despite the availability of Bacille Calmette Guérin (BCG) vaccine and chemotherapy. A better understanding of how immune system controls TB and latent TB is critical for understanding disease pathogenesis and for devising immune-mediated strategies for prevention and treatment of disease. A brief update on the immunopathogenesis of TB will be provided, and how this knowledge can be used for rational vaccine design will be briefly addressed. Due to poor BCG protective efficacy in humans, there is currently a great deal of activity in new vaccine development. Various vaccine candidates; BCG replacement vaccines including recombinant BCG; live-attenuated Mycobacterium tuberculosis; and booster vaccines such as vaccinia virus overexpressing antigen 85, nucleic acid vaccines, and subunit protein vaccines with novel adjuvants, are at different stages of development. There is significant interest in using a prime-boost strategy for improved vaccine efficacy. However, the optimal dose, route, frequency and timing of the booster vaccines remain to be determined, and the potential side effects of booster vaccines in causing increased pathology needs to be tested. The recent genome sequencing of avirulent strain M. tuberculosis H37Ra provides a rational approach for reconstructing a new live-attenuated vaccine that could be even more attenuated than BCG and useful for HIV-positive and HIV-negative settings. The challenges of TB vaccine development such as lack of immune markers for protection in humans, shortage of clinical trial sites, lengthy time required for vaccine evaluation, and the high cost will also be briefly discussed.
ASJC Scopus subject areas
- Pulmonary and Respiratory Medicine