{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,18]],"date-time":"2026-10-18T13:15:47Z","timestamp":1792329347793,"version":"4.4.0"},"update-to":[{"DOI":"10.1371\/journal.ppat.1010409","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2022,4,7]],"date-time":"2022-04-07T00:00:00Z","timestamp":1649289600000}}],"reference-count":59,"publisher":"Public Library of Science (PLoS)","issue":"3","license":[{"start":{"date-parts":[[2022,3,28]],"date-time":"2022-03-28T00:00:00Z","timestamp":1648425600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/publicdomain\/zero\/1.0\/"}],"funder":[{"name":"PATH Malaria Vaccine Initiative"},{"DOI":"10.13039\/100000865","name":"Bill and Melinda Gates Foundation","doi-asserted-by":"publisher","award":["OPP1170236"],"award-info":[{"award-number":["OPP1170236"]}],"id":[{"id":"10.13039\/100000865","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000865","name":"Bill and Melinda Gates Foundation","doi-asserted-by":"publisher","award":["INV-004923"],"award-info":[{"award-number":["INV-004923"]}],"id":[{"id":"10.13039\/100000865","id-type":"DOI","asserted-by":"publisher"}]},{"name":"U.S. Agency for International Development (USAID) Innovations in Malaria Vaccine Development","award":["7200AA20C00017"],"award-info":[{"award-number":["7200AA20C00017"]}]},{"DOI":"10.13039\/100015283","name":"Bloomberg Philanthropies","doi-asserted-by":"crossref","id":[{"id":"10.13039\/100015283","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["www.plospathogens.org"],"crossmark-restriction":false},"short-container-title":["PLoS Pathog"],"abstract":"<jats:p>Potent and durable vaccine responses will be required for control of malaria caused by <jats:italic>Plasmodium falciparum (Pf)<\/jats:italic>. RTS,S\/AS01 is the first, and to date, the only vaccine that has demonstrated significant reduction of clinical and severe malaria in endemic cohorts in Phase 3 trials. Although the vaccine is protective, efficacy declines over time with kinetics paralleling the decline in antibody responses to the <jats:italic>Pf<\/jats:italic> circumsporozoite protein (<jats:italic>Pf<\/jats:italic>CSP). Although most attention has focused on antibodies to repeat motifs on <jats:italic>Pf<\/jats:italic>CSP, antibodies to other regions may play a role in protection. Here, we expressed and characterized seven monoclonal antibodies to the C-terminal domain of CSP (ctCSP) from volunteers immunized with RTS,S\/AS01. Competition and crystal structure studies indicated that the antibodies target two different sites on opposite faces of ctCSP. One site contains a polymorphic region (denoted \u03b1-ctCSP) and has been previously characterized, whereas the second is a previously undescribed site on the conserved \u03b2-sheet face of the ctCSP (denoted \u03b2-ctCSP). Antibodies to the \u03b2-ctCSP site exhibited broad reactivity with a diverse panel of ctCSP peptides whose sequences were derived from field isolates of <jats:italic>P<\/jats:italic>. <jats:italic>falciparum<\/jats:italic> whereas antibodies to the \u03b1-ctCSP site showed very limited cross reactivity. Importantly, an antibody to the \u03b2-site demonstrated inhibition activity against malaria infection in a murine model. This study identifies a previously unidentified conserved epitope on CSP that could be targeted by prophylactic antibodies and exploited in structure-based vaccine design.<\/jats:p>","DOI":"10.1371\/journal.ppat.1010409","type":"journal-article","created":{"date-parts":[[2022,3,28]],"date-time":"2022-03-28T17:29:06Z","timestamp":1648488546000},"page":"e1010409","update-policy":"https:\/\/doi.org\/10.1371\/journal.ppat.corrections_policy","source":"Crossref","is-referenced-by-count":41,"title":["A novel CSP C-terminal epitope targeted by an antibody with protective activity against Plasmodium falciparum"],"prefix":"10.1371","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3240-9524","authenticated-orcid":true,"given":"Nathan","family":"Beutler","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tossapol","family":"Pholcharee","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David","family":"Oyen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7230-3834","authenticated-orcid":true,"given":"Yevel","family":"Flores-Garcia","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4566-1481","authenticated-orcid":true,"given":"Randall S.","family":"MacGill","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1097-6723","authenticated-orcid":true,"given":"Elijah","family":"Garcia","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4812-3168","authenticated-orcid":true,"given":"Jaeson","family":"Calla","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mara","family":"Parren","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Linlin","family":"Yang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wayne","family":"Volkmuth","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1944-8473","authenticated-orcid":true,"given":"Emily","family":"Locke","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jason A.","family":"Regules","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sheetij","family":"Dutta","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8754-9201","authenticated-orcid":true,"given":"Daniel","family":"Emerling","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3169-2324","authenticated-orcid":true,"given":"Angela M.","family":"Early","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1665-9323","authenticated-orcid":true,"given":"Daniel E.","family":"Neafsey","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elizabeth A.","family":"Winzeler","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8860-0419","authenticated-orcid":true,"given":"C. Richter","family":"King","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1414-6196","authenticated-orcid":true,"given":"Fidel","family":"Zavala","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6711-9864","authenticated-orcid":true,"given":"Dennis R.","family":"Burton","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6469-2419","authenticated-orcid":true,"given":"Ian A.","family":"Wilson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas F.","family":"Rogers","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2022,3,28]]},"reference":[{"key":"ppat.1010409.ref001","doi-asserted-by":"crossref","DOI":"10.30875\/60123dd4-en","volume-title":"World malaria report 2020","author":"World Health Organization","year":"2020"},{"key":"ppat.1010409.ref002","doi-asserted-by":"crossref","first-page":"452","DOI":"10.1186\/1475-2875-13-452","article-title":"Artemisinin resistance\u2014modelling the potential human and economic costs.","volume":"13","author":"Y Lubell","year":"2014","journal-title":"Malar J"},{"key":"ppat.1010409.ref003","volume-title":"Artemisinin resistance and artemisinin-based combination therapy efficacy: status report:","author":"World Health Organization","year":"2018"},{"issue":"9906","key":"ppat.1010409.ref004","doi-asserted-by":"crossref","first-page":"1700","DOI":"10.1016\/S0140-6736(13)62238-2","article-title":"Malaria vaccine technology roadmap","volume":"382","author":"VS Moorthy","year":"2013","journal-title":"Lancet"},{"key":"ppat.1010409.ref005","volume-title":"Global Technical Strategy for Malaria 2016\u20132030:","author":"World Health Organization","year":"2015"},{"issue":"20","key":"ppat.1010409.ref006","doi-asserted-by":"crossref","first-page":"1863","DOI":"10.1056\/NEJMoa1102287","article-title":"Clinical Trial Partnerships. 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avidity of sporozoite-specific antibodies associate with protection status and distinguish among RTS,S\/AS01 dose regimens.","volume":"8","author":"SM Dennison","year":"2020","journal-title":"Open Forum Infect Dis"},{"issue":"21","key":"ppat.1010409.ref031","doi-asserted-by":"crossref","first-page":"2025","DOI":"10.1056\/NEJMoa1505819","article-title":"Genetic diversity and protective efficacy of the RTS,S\/AS01 malaria vaccine","volume":"373","author":"DE Neafsey","year":"2015","journal-title":"N Engl J Med"},{"issue":"8","key":"ppat.1010409.ref032","doi-asserted-by":"crossref","first-page":"e43430","DOI":"10.1371\/journal.pone.0043430","article-title":"Genetic variation in the Plasmodium falciparum circumsporozoite protein in India and its relevance to RTS,S malaria vaccine","volume":"7","author":"M Zeeshan","year":"2012","journal-title":"PLoS 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