Malaria antigens targeted by antibody-dependent cellular inhibition

Dr. J. McBride

Understanding of how parasites are controlled by the immune system is a major question in the development of malaria vaccines. Protection of malaria patients by passively transferred immune IgG established that antibodies are an important component of human immunity against blood stages of P.falciparum. Studies addressing the question of how IgG might mediate the protection, indicate that cytophilic subclasses act synergistically with monocytes in so-called antibody-dependent cellular inhibition (ADCI, an in vitro measure of anti-parasite immunity). Target antigens of antibodies functional in ADCI remain to be defined in molecular terms.

This project will investigate immune recognition of defined merozoite proteins that are candidates for P.falciparum vaccine, and test whether such antigens mediate ADCI. Recombinant proteins modelling selected domains of the parasite antigens will be used to affinity-purify specific antibody subpopulations for ADCI and also for direct antibody-mediated inhibition of the parasite in culture. Antigenically distinct parasite clones will be used to evaluate the contribution of antibodies against polymorphic epitopes, and to compare their efficiency with that of responses against more conserved regions or molecules.

The projects involve collaborative links in countries where malaria is endemic, and would suit students with background in immunology, molecular or population biology.