There’s an interesting report in “Infection and Immunity” this week about the development of a safer and more effective tuberculosis (TB) vaccine (1), something that is certainly needed as the rate of TB infection is rising in many countries.
A major problem for the current TB vaccine, the BCG vaccine first developed in the 1920’s, is that it is a live attenuated tuberculosis bacterium and so cannot be given to individuals whose immune system is compromised since even a weakened bacteria can cause deadly disease if the immune system is not functioning properly. This is a serious problem, especially in countries such as South Africa where there are high rates of HIV infection and a growing problem of multi-drug resistant TB. The effectiveness of the BCG vaccine in preventing TB infection is also lower than ideal, though it is very effective at preventing tuberculosis meningitis,and a new vaccine that can confer better protection is highly desirable.
Scientists at UCLA have developed a vaccine, given the name rBCG(mbtB)30, that promises to be both more effective at preventing TB infection and safer than the existing vaccine. They did this by genetically altering an improved BCG strain called rBCG30 that they had previously developed so that it now lacked a scavenger protein needed to obtain iron from its environment. rBCG(mbtB)30 only undergoes a limited number of cell divisions after vaccination, a change that the UCLA team hoped would severely limit its potential to multiply and cause disease in immunocompromised individuals.
To verify that the new vaccine had not lost it’s improved ability to protect against infection Marcus Horwitz and his colleagues turned to the guinea pig. The guinea pig is an animal in which TB infection closely resembles human disease clinically, immunologically, and pathologically, and which has played an important role in TB research for over a hundred years, both in the development of antibiotics to treat the disease and vaccines to prevent it. They found that the new vaccine gave greater protection than the current BCG vaccine, though it wasn’t quite as good as their previous rBCG30 vaccine. To evaluate the potential of the new vaccine to cause disease in individuals with compromised immune systems they turned to another animal model, the severe combined immunodeficiency (SCID) mouse that completely lacks an immune system. In SCID mice rBCG(mbtB)30 was found to be safer than the existing BGC vaccine, with fewer animals developing lethal TB infections.
This vaccine is very promising and a significant advance in terms of both safety and effectiveness over existing TB vaccines, though it still has room for improvement so I would ideally like to see it developed further before it is tested in human clinical trials. Having said that it is without doubt a step in the right direction, showing that a TB vaccine can be made simultaneously more effective and safer for individuals with weakened immune systems.
1) Tullius M.V. et al. “A Replication-Limited Recombinant Mycobacterium bovis BCG vaccine against tuberculosis designed for human immunodeficiency virus-positive persons is safer and more efficacious than BCG.” Infection and Immunity p. 5200-5214, Volume 76, No. 11, pages 5200-5214 (2008). DOI:10.1128/IAI.00434-08