Human monoclonal antibodies against Plasmodium falciparum transmission

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Talk abstract:

Malaria transmission blocking vaccines (TBVs) aim to induce human antibodies that interrupt malaria parasite development in the mosquito and thereby provide much needed tools for malaria control and elimination efforts. The parasite surface proteins Pfs48/45 and Pfs230 are leading TBV candidates. We isolated approximately 100 human Pfs48/45- and Pfs230-specific monoclonal antibodies (mAbs) from donors naturally exposed to malaria. I will present binding and functional data, as well as X-ray crystallography co-crystal structures of mAb-antigen complexes. Together these data provide unprecedented insight into protective and non-protective epitopes that can inform the design of refined malaria transmission blocking vaccine candidates. Furthermore, I will present the results of a first-in-human clinical trial with a highly potent humanized transmission blocking antibody, TB31F, demonstrating it is safe and retains efficacy after i.v. and s.c. administration.