Tuberculosis
TB vaccines will fail in developing countries
By UCL
Sep 4, 2005 - 9:38:00 AM

Tuberculosis (TB) vaccines currently on trial at a cost of hundreds of millions of dollars will fail to protect populations living close to the Equator, warns a review published in Nature Reviews Immunology . Scientists from UCL (University College London) warn that vaccines designed in the developed world do not take into account differences in immune systems across the globe. They recommend greater use of �negative vaccination' in drug design, to prevent the West from developing TB vaccines destined to fail in Asia, Africa and Latin America, where an effective vaccine is most needed.

As described in the review, funded by the British Lung Foundation, the UCL team has explored variations in immune responses to TB bacteria and has found that in developing countries, the bacteria trigger a corrupted response which converts the body's protective system into a harmful one.

In the northern hemisphere, the immune system typically protects the body from TB via Th1 cells which lead the immune response. However, for populations living close to the Equator, UCL scientists have found that this response becomes immunopathological because of the simultaneous activation of inappropriate response mechanisms. This not only prevents the body from eliminating the bacteria, but also causes bacteria-rich lung cavities to form, which enable the infection to spread further.

The UCL scientists warn that TB vaccines currently on trial are typically designed to boost the Th1 cell response, which in principle works in Europe or northern parts of USA . However, for the vaccine to work successfully in equatorial countries, it would need to suppress the inappropriate response mechanisms that cause immunopathology rather than increase Th1 cells. The UCL team recommends more intelligent use of � negative vaccination', which involves the use of vaccines that suppress damaging immune responses.

Professor Graham Rook, of the UCL Centre for Infectious Diseases and International Health, says: �It is already known that the BCG vaccine works in the northern hemisphere but not close to the Equator, where countries within 30 degrees latitude of the Equator have the greatest failure rates. Yet vaccine design continues to ignore crucial differences in immune systems between populations.

�We are not saying that funding for TB vaccination in developing countries should be stopped � quite the contrary, given that TB kills between 2 and 3 million people every year. But we are concerned that the BCG vaccine is failing these countries and that TB vaccines currently on trial are likely to go the same way.

�What we are arguing for is �negative vaccination', where a vaccine is designed to reduce rather than increase its target mechanism. We believe this method will work for TB vaccination in equatorial countries, where it would appear that some steps in the body's immune response need to be dampened down or switched off. This approach might also work for other problematic infections such as HIV, and would certainly be worth exploring.

�The irony is that variations in the immune system are intensely studied when it comes to seeking explanations for the increases in chronic inflammatory disorders such as allergies or inflammatory bowel disease in wealthy countries, but few people think about the significance of the differences in relation to the problems of poor countries and vaccine development.�

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