biostudies-literatureKo KTMedical Research CouncilWellcome Trust5603https://www.ebi.ac.uk/biostudies/studies/S-EPMC9509318biostudies-literatureUnknown13(1)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 structure of full-length Pfs48/45, showing its three domains to form a dynamic, planar, triangular arrangement. We reveal where transmission-blocking and non-blocking antibodies bind on Pfs48/45. Finally, we demonstrate that antibodies which bind across this Nature communicationsStructure of the malaria vaccine candidate Pfs48/45 and its recognition by transmission blocking antibodies.PMC9509318MR/R001138/1220797/Z/20/ZMekhaiel DMiura KLong CAHiggins MKJore MMBiswas SDeuker DJKo KTLennartz FGuloglu BMarini AfalseStructure of the malaria vaccine candidate Pfs48/45 and its recognition by transmission blocking antibodies.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 structure of full-length Pfs48/45, showing its three domains to form a dynamic, planar, triangular arrangement. We reveal where transmission-blocking and non-blocking antibodies bind on Pfs48/45. Finally, we demonstrate that antibodies which bind across this 2022-01-01T00:00:00Z2022 Sep2026-06-01T02:26:13.353Z2026-04-08T09:13:31.349ZS-EPMC95093183615331710.1038/s41467-022-33379-6