Differences Between Immune Systems in Rich and Developing Countries: Implications for the Design of Tuberculosis Vaccines that will work in the Countries that need them
BCG, the only licensed vaccine for TB, is effective in rich Northern countries, but usually fails to protect against adult TB in developing countries. New candidate vaccines are entering trials. It will be tragic if these new candidates fail in the same places as BCG, and for the same reasons. Paradoxically a lot of effort is going into understanding how the immune systems of people living in rich countries differ from the immune systems of people living in developing ones, but this is motivated by the “hygiene hypothesis” and seeks to explain increases in chronic inflammatory disorders (allergies, autoimmunity, inflammatory bowel disease) in the rich countries. The new knowledge obtained is being exploited in exciting clinical trials for the rich, but is rarely applied to the problem of creating TB vaccines for poor countries. The situation is aggravated by the unavoidable use of BCG as a “Gold Standard” in animal models of TB used to select vaccine candidates. Not only does this “Gold Standard” fail in man where it is needed, but it also fails in mouse models. A vaccine for man must stop development of disease after exposure to TB, but in mice BCG only delays death by a few weeks. Such an effect would not be detected or relevant in human studies. Finally, TB in developing countries results from high dose challenge in people who are already partially immunised by environmental mycobacteria, and often infected with helminths. Vaccine candidates, by contrast, are screened in specific pathogen-free animals that bear no immunological resemblance to the citizens of countries where a vaccine is needed. In this talk we will suggest ways in which our effort can be more precisely targeted to the populations and countries that need it.