TY - JOUR T1 - Structure of the malaria vaccine candidate Pfs48/45 and its recognition by transmission blocking antibodies JF - bioRxiv DO - 10.1101/2022.05.24.493318 SP - 2022.05.24.493318 AU - Kuang-Ting Ko AU - Frank Lennartz AU - David Mekhaiel AU - Bora Guloglu AU - Arianna Marini AU - Danielle J. Deuker AU - Carole A. Long AU - Matthijs M. Jore AU - Kazutoyo Miura AU - Sumi Biswas AU - Matthew K. Higgins Y1 - 2022/01/01 UR - http://biorxiv.org/content/early/2022/05/25/2022.05.24.493318.abstract N2 - An effective malaria vaccine remains a global health priority and vaccine immunogens which prevent transmission of the parasite will have important roles in multi-component vaccines. One of the most promising candidates for inclusion in a transmission-blocking malaria vaccine is the gamete surface protein Pfs48/45, which is essential for development of the parasite in the mosquito midgut. Indeed, antibodies which bind Pfs48/45 can prevent transmission if ingested with the parasite as part of the mosquito bloodmeal. Here we present the first structure of full-length Pfs48/45, revealing its three domains to form a dynamic, planar, triangular arrangement. From this, we show where transmission-blocking and non-blocking antibodies bind on Pfs48/45. Finally, we demonstrate that antibodies which bind across this molecule can be transmission-blocking. These studies will guide the development of future Pfs48/45-based vaccine immunogens.Competing Interest StatementThe authors have declared no competing interest. ER -