Understanding a malaria transmission blocking antibody

What is the molecular basis of action of a malaria transmission blocking antibody?

An essential stage in the life cycle of the malaria parasite is the fusion of its gametes within a mosquito. Antibodies which prevent this will also block parasite development and will prevent transmission of the disease when the mosquito bites another human.

A promising target for effective transmission blocking antibodies is Pfs48/45, a protein found on the gamete surface. If the mosquito ingests antibodies against Pfs48/45 in its blood meal, these prevent gamete fusion. This makes Pfs48/45 a prime candidate as a transmission blocking component of a malaria vaccine.

In this study, we teamed up with Sumi Biswas’ group to investigate how Pfs48/45-targeting antibodies bind, studying a new panel of antibodies raised by Florian Brod as well as the most effective antibody previously identified, 45.1. Frank Lennartz and Florian mapped the binding sites and assessed the transmission blocking potential of this antibody panel. Frank was also able to determine the structure of 45.1 in complex with the C-terminal domain of Pfs48/45, revealing the molecular nature of its epitope.

This study provided the first detailed structural insight into a transmission-blocking antibody epitope and will guide future vaccine design.

Lennartz, F., Brod,F, Dabbs, R, Miura, K, Mekhaiel, D, Marini, A, Jore, M.M., Søgaard, M.M, Jørgensen, T., de Jongh, W.A., Sauerwein, R.W., Long, C.A., Biswas, S.* and Higgins, M.K*. (2018) Structural basis for recognition of the malaria vaccine candidate Pfs48/45 by a transmission blocking antibody. Nature Communications 9 3822