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The structural basis and mechanisms of CelTOS-induced protective immunity to parasites are unknown. Here, CelTOS-specific monoclonal antibodies (mAbs) 7g7 and 4h12 demonstrated multistage activity, protecting against liver infection and preventing parasite transmission to mosquitoes. Both mAbs demonstrated cross-species activity with sterile protection against in vivo challenge with transgenic parasites containing either\n                    <jats:italic>P. falciparum<\/jats:italic>\n                    or\n                    <jats:italic>P. vivax<\/jats:italic>\n                    CelTOS, and with transmission reducing activity against\n                    <jats:italic>P. falciparum<\/jats:italic>\n                    . The mAbs prevented CelTOS-mediated pore formation providing insight into the protective mechanisms. X-ray crystallography and mutant-library epitope mapping revealed two distinct broadly conserved neutralizing epitopes. 7g7 bound to a parallel dimer of CelTOS, while 4h12 bound to a novel antiparallel dimer architecture. These findings inform the design of antibody therapies and vaccines and raise the prospect of a single intervention to simultaneously combat\n                    <jats:italic>P. falciparum<\/jats:italic>\n                    and\n                    <jats:italic>P. vivax<\/jats:italic>\n                    malaria.\n                  <\/jats:p>","DOI":"10.1038\/s41467-024-51701-2","type":"journal-article","created":{"date-parts":[[2024,8,29]],"date-time":"2024-08-29T09:02:53Z","timestamp":1724922173000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["Multistage protective anti-CelTOS monoclonal antibodies with cross-species sterile protection against malaria"],"prefix":"10.1038","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3209-1675","authenticated-orcid":false,"given":"Wai Kwan","family":"Tang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nichole D.","family":"Salinas","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6125-0036","authenticated-orcid":false,"given":"Surendra Kumar","family":"Kolli","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shulin","family":"Xu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Darya V.","family":"Urusova","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hirdesh","family":"Kumar","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John R.","family":"Jimah","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8685-0900","authenticated-orcid":false,"given":"Pradeep Annamalai","family":"Subramani","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Madison M.","family":"Ogbondah","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Samantha J.","family":"Barnes","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3707-7979","authenticated-orcid":false,"given":"John H.","family":"Adams","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2689-1337","authenticated-orcid":false,"given":"Niraj H.","family":"Tolia","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2024,8,29]]},"reference":[{"key":"51701_CR1","unstructured":"WHO. 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