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Comprising 3135 amino acids (aa), the large size of Pfs230 necessitates the use of sub-fragments as vaccine immunogens. Therefore, determination of which regions induce functional antibody responses is essential. We previously reported that of 27 sub-fragments spanning the entire molecule, only five induced functional antibodies. A \u201cfunctional\u201d antibody is defined herein as one that inhibits<jats:italic>Plasmodium falciparum<\/jats:italic>parasite development in mosquitoes in a standard membrane-feeding assay (SMFA). These five sub-fragments were found within the aa 443\u20131274 range, and all contained aa 543\u2013730. Here, we further pinpoint the location of epitopes within Pfs230 that are recognized by functional antibodies using antibody depletion and enrichment techniques. Functional epitopes were not found within the aa 918\u20131274 region. Within aa 443\u2013917, further analysis showed the existence of functional epitopes not only within the aa 543\u2013730 region but also outside of it. Affinity-purified antibodies using a synthetic peptide matching aa 543\u2013588 showed activity in the SMFA. Immunization with a synthetic peptide comprising this segment, formulated either as a carrier-protein conjugate vaccine or with a liposomal vaccine adjuvant system, induced antibodies in mice that were functional in the SMFA. These findings provide key insights for Pfs230-based vaccine design and establish the feasibility for the use of synthetic peptide antigens for a malaria TBV.<\/jats:p>","DOI":"10.1038\/s41541-021-00423-3","type":"journal-article","created":{"date-parts":[[2022,1,13]],"date-time":"2022-01-13T11:03:33Z","timestamp":1642071813000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":22,"title":["Elucidating functional epitopes within the N-terminal region of malaria transmission blocking vaccine antigen Pfs230"],"prefix":"10.1038","volume":"7","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4455-2432","authenticated-orcid":false,"given":"Kazutoyo","family":"Miura","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9070-8499","authenticated-orcid":false,"given":"Eizo","family":"Takashima","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Thao P.","family":"Pham","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bingbing","family":"Deng","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Luwen","family":"Zhou","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wei-Chiao","family":"Huang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ababacar","family":"Diouf","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yonas T.","family":"Gebremicale","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mayumi","family":"Tachibana","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tomoko","family":"Ishino","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"C.","family":"Richter King","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9052-884X","authenticated-orcid":false,"given":"Jonathan F.","family":"Lovell","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Carole A.","family":"Long","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7415-1325","authenticated-orcid":false,"given":"Takafumi","family":"Tsuboi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2022,1,13]]},"reference":[{"key":"423_CR1","unstructured":"World Health Organization. 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The other authors declare no competing interests.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"4"}}