Structure of the malaria vaccine candidate Pfs48/45 and its recognition by transmission blocking antibodies

Ko, K.-T.; Lennartz, F.; Mekhaiel, D.; Guloglu, B.; Marini, A.; Deuker, D.; Long, C.; Jore, M.; Miura, K.; Biswas, S.; Higgins, M. K.

doi:10.1101/2022.05.24.493318

bioRxiv · 10.1101/2022.05.24.493318

Structure of the malaria vaccine candidate Pfs48/45 and its recognition by transmission blocking antibodies

Ko, K.-T.·Lennartz, F.·Mekhaiel, D.·Guloglu, B.·Marini, A.·Deuker, D.·Long, C.·Jore, M.·Miura, K.·Biswas, S.·Higgins, M. K.

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Abstract

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.

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Ko, K.-T., Lennartz, F., Mekhaiel, D., Guloglu, B., Marini, A., Deuker, D., Long, C., Jore, M., Miura, K., Biswas, S., Higgins, M. K.. 2022-05-25. Structure of the malaria vaccine candidate Pfs48/45 and its recognition by transmission blocking antibodies. https://doi.org/10.1101/2022.05.24.493318

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