biostudies-literatureUnknown479(24)Dietrich MHTransmission blocking interventions can stop malaria parasite transmission from mosquito to human by inhibiting parasite infection in mosquitos. One of the most advanced candidates for a malaria transmission blocking vaccine is Pfs230. Pfs230 is the largest member of the 6-cysteine protein family with 14 consecutive 6-cysteine domains and is expressed on the surface of gametocytes and gametes. Here, we present the crystal structure of the first two 6-cysteine domains of Pfs230. We identified high affinity Pfs230-specific nanobodies that recognized gametocytes and bind to distinct sites on Pfs230, which were isolated from immunized alpacas. Using two non-overlapping Pfs230 nanobodies, we show that these nanobodies significantly blocked P. falciparum transmission and reduced the formation ofThe Biochemical journal2529-2546https://www.ebi.ac.uk/biostudies/studies/S-EPMC9788556biostudies-literatureNanobodies against Pfs230 block Plasmodium falciparum transmission.PMC9788556Keremane SAdair ACowman AFChan LJHealer JLopaticki SReaksudsan KDixon MWAO'Neill MTDietrich MHTrickey SGabriela MTham WHTan LLfalseNanobodies against Pfs230 block Plasmodium falciparum transmission.Transmission blocking interventions can stop malaria parasite transmission from mosquito to human by inhibiting parasite infection in mosquitos. One of the most advanced candidates for a malaria transmission blocking vaccine is Pfs230. Pfs230 is the largest member of the 6-cysteine protein family with 14 consecutive 6-cysteine domains and is expressed on the surface of gametocytes and gametes. Here, we present the crystal structure of the first two 6-cysteine domains of Pfs230. We identified high affinity Pfs230-specific nanobodies that recognized gametocytes and bind to distinct sites on Pfs230, which were isolated from immunized alpacas. Using two non-overlapping Pfs230 nanobodies, we show that these nanobodies significantly blocked P. falciparum transmission and reduced the formation of2022-01-01T00:00:00Z2022 Dec2026-05-27T21:03:23.1Z2025-02-18T22:34:35.487ZS-EPMC97885563652010810.1042/BCJ20220554