TB vaccines could increase disease risk

Vaccines designed to prevent TB could be putting people at risk of developing another strand of the killer disease, research has revealed.

Researchers from the University of Bristol found that new vaccines which remove one strain of tuberculosis can allow previously suppressed strains to thrive.

It means that widespread immunisation programmes could actually help the disease become resistant to the drugs designed to stop it spreading.

The research, which was carried out with experts in the USA, used mathematical models to show the different ways in which the disease may react to drugs designed to destroy it.

TB is caused by infection with the bacterium Mycobacterium tuberculosis. There are nearly nine million new cases of TB each year and two million deaths world wide.

A major priority in medical research is the development of new, more effective anti-TB vaccines. To date, this effort has yielded more than 200 new vaccine candidates, many of which are now undergoing animal testing and early clinical trials.

However, recent research has revealed many different strains of the disease which each respond in different ways to different drugs.

Experts have yet to understand the full complexity of the issue but West researchers have concluded that there is a downside to many of the new vaccines.

Dr Caroline Colijn, from Bristol University, said: "In most scenarios increasing vaccine coverage reduces the overall TB burden.

"However, the benefits are reduced if the preferential removal of one strain allows a previously suppressed strain to succeed. We found that there is a possibility that TB prevalence may increase due to a vaccination program effective against a dominant strain, if that strain didn't provoke a good immune response.

"This creates a concern that vaccination policies could affect which strains are present in a population, potentially releasing strains with an increased potential for drug resistance, and could even result in an increase in disease levels."

This phenomenon has already been observed for other pathogens, including streptococcus pneumonia, the bacterium that can cause pneumonia, and Haemophilus influenza, common bacteria that cause a wide variety of infections in children.

Even in scenarios when vaccination does not cause any such perverse effect, it affects the strain composition in the population through selective pressure, and this could be a cause for concern.

Dr Colijn said: "Our results indicate that the public health benefit of new TB vaccines and vaccination programs will depend critically on the diversity of circulating strains, the in-host competition between the strains and on the strain specificity of the vaccines."

She said that larger studies of diverse clinical strains would help to determine variability of target vaccine antigens and said that new vaccines should be tested against as wide a variety of clinical strains as possible.

The findings are published this week in the Proceedings of the National Academy of Sciences.