Vaccine development for Tuberculosis: Past, Present and Future Challenges

About one third of the world's population is infected with Mycobacterium tuberculosis (M. tb), and new infections occur at a rate of about one per second. Additionally, more people in the developed world contact tuberculosis (TB) because their immune systems are more likely to be compromised due to higher exposure to immunosuppressive drugs, substance abuse, or AIDS. The distribution of tuberculosis is not uniform across the globe, still the treatment is difficult and requires long courses of multiple antibiotics. However, antibiotic resistance is a growing problem in multidrugresistant (MDR) tuberculosis. But mostly the prevention relies on screening programs and vaccination, usually with Bacillus Calmette- Guérin (BCG) vaccine. BCG is the most commonly used vaccine worldwide, but not as a powerful vaccine. BCG also provides some protection against severe forms of pediatric TB, but has been shown to be unreliable against adult pulmonary TB which accounts for most of the disease burden worldwide. Currently, there is an urgent need for novel, more effective vaccine that can prevent all forms of TB including drug resistant strains for all age groups and among people with HIV. The first recombinant tuberculosis vaccine rBCG30, entered clinical trials in year 2004, but, still no effective vaccine is available in a market. Study showed that DNA TB vaccine given with conventional chemotherapy can accelerate the disappearance of bacteria as well as protect against re-infection in mice and it is quite effective against TB. A very promising TB vaccine, MVA85A, is currently in phase II trials and is based on a genetically modified vaccinia virus. Many other strategies are also being used to develop novel vaccines, including both subunit vaccines such as Hybrid-1, HyVac4 or M72, and recombinant adenoviruses such as Ad35. Some of these vaccines can be effectively administered without needles making them preferable for areas where HIV is very common and few of these vaccines have been successfully tested in humans and are now in extended testing in TB-endemic regions. To encourage further discovery, researchers and policymakers across the globe are promoting new economic models of vaccine development including prices, tax incentives and advance market commitments. This review gives the basic idea of various vaccine development approaches and its effective application in TB control.

Author(s): Dileep Tiwari, Shafiul Haque and Ramesh Chandra

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