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Improvement of BCG by modification of its immunosuppressive glycolipids

Thursday 29 May 2014

Dr Peter van der Ley

Tuberculosis (TB), a disease caused by the bacterium Mycobacterium tuberculosis, kills about 2-3 million people per year. A vaccine for TB is available: it is an attenuated strain of M. Bovis called Bacille Calmette-Guerin (BCG). BCG was developed in 1921 and hundreds of millions of children have been vaccinated since. Protection mediated by BCG is unsatisfactory: while it protects relatively well against childhood tuberculosis, in particular meningitis, protection wanes and BCG protects much less against pulmonary manifestations in adults. The reason why BCG does not protect well is unknown, but clear is that both BCG and M. tuberculosis suppress the immune response of the host The suppression of an adequate host response may prevent BCG from eliciting an optimal, protective response. We are therefore investigating the possibility to improve BCG by constructing mutant strains that are less immunosuppressive. To this end, we are targeting various mycobacterial glycolipids for which an immunomodulatory effect has been demonstrated, and constructing and analyzing BCG strains in which their biosynthesis has been altered.

Recombinant DNA methods, immunological techniques, bacteriological techniques

6 or 9 months

Dr P. van der Ley, peter.van.der.ley@intravacc.nl