{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,23]],"date-time":"2026-08-23T18:21:04Z","timestamp":1787509264763,"version":"build-2736575974"},"update-to":[{"DOI":"10.1371\/journal.pmed.1004877","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2026,5,19]],"date-time":"2026-05-19T00:00:00Z","timestamp":1779148800000}}],"reference-count":63,"publisher":"Public Library of Science (PLoS)","issue":"5","license":[{"start":{"date-parts":[[2026,5,14]],"date-time":"2026-05-14T00:00:00Z","timestamp":1778716800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000925","name":"National Health and Medical Research Council","doi-asserted-by":"publisher","award":["2033320"],"award-info":[{"award-number":["2033320"]}],"id":[{"id":"10.13039\/501100000925","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000925","name":"National Health and Medical Research Council","doi-asserted-by":"publisher","award":["2018654"],"award-info":[{"award-number":["2018654"]}],"id":[{"id":"10.13039\/501100000925","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100005627","name":"Thrasher Research Fund","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100005627","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001043","name":"Cass Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001043","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Research Training Program Scholarship, Australian Government"},{"name":"Research Training Program Scholarship, Australian Government"},{"name":"Research Training Program Scholarship, Australian Government"},{"name":"Research Training Program Scholarship, Australian Government"},{"name":"NHMRC for Independent Research Institutes Infrastructure Support Scheme","award":["2018654"],"award-info":[{"award-number":["2018654"]}]},{"name":"Victorian State Government Operational Infrastructure Support"},{"name":"CERCA Program, Generalitat de Catalunya"},{"name":"Spanish Agency for International Cooperation and Development"},{"name":"Spanish Agency for International Cooperation and Development"}],"content-domain":{"domain":["www.plosmedicine.org"],"crossmark-restriction":false},"short-container-title":["PLoS Med"],"abstract":"<jats:sec id=\"sec001\">\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>\n                      The RTS,S\/AS01 malaria vaccine was recently approved for implementation in children, but only provides modest and short-lived efficacy against malaria. RTS,S targets a portion of the\n                      <jats:italic>Plasmodium falciparum<\/jats:italic>\n                      (\n                      <jats:italic>Pf<\/jats:italic>\n                      ) circumsporozoite protein (CSP), comprising the central NANP-repeat region and C-terminal domain. Mechanisms of immunity and correlates of protection for the RTS,S vaccine are not well defined, hindering progress towards generating highly effective CSP-based vaccines.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"sec002\">\n                    <jats:title>Methods and findings<\/jats:title>\n                    <jats:p>\n                      We investigated epitope specificity and cross-reactivity of vaccine-induced antibodies to six peptides representing CSP epitopes in the N-terminal and central NANP-repeat region. We evaluated antibody reactivity in preclinical mouse vaccine studies, among CSP-specific monoclonal antibodies (mAbs), and in a large RTS,S phase IIb clinical trial in young children 1\u20134 years old (\n                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u2009735).\n                    <\/jats:p>\n                    <jats:p>\n                      The preclinical mouse vaccine studies and CSP-specific mAbs were used to initially evaluate IgG responses to the six peptides. Mice immunised with the central NANP-repeat region had IgG with cross-reactivity to an epitope in the N-terminal region. Additionally, we demonstrated that a single CSP-specific mAb could display cross-reactivity to several CSP epitopes. Through post hoc quantification and analysis of antibody responses in the RTS,S phase IIb clinical trial, we found that a subset of children generated IgG with specificity for a short NANP-repeat epitope (NANP\n                      <jats:sub>2<\/jats:sub>\n                      ; amino acid sequence: NANPNANP) and cross-reactivity to an N-terminal epitope (J1; amino acid sequence: KQPADGNPDPNANPN). Notably, children with high IgG responses to NANP\n                      <jats:sub>2<\/jats:sub>\n                      and J1 had a significantly reduced risk of clinical malaria, compared to children with low responses (IgG to NANP\n                      <jats:sub>2<\/jats:sub>\n                      (aHR: 0.838 (95% CI [0.716, 0.981];\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.028)) and J1 (aHR: 0.718 (95% CI [0.611, 0.844];\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.001)), and these responses were also associated with higher antibody Fc-mediated functional activities. We have evaluated NANP\n                      <jats:sub>2<\/jats:sub>\n                      and J1 as immunological correlates of protection in one phase IIb cohort, additional studies in other RTS,S and R21 cohorts will be important to further confirm our findings.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"sec003\">\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>These findings reveal promising new correlates of protection for RTS,S and new insights to inform the development of next-generation malaria vaccines.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1371\/journal.pmed.1004877","type":"journal-article","created":{"date-parts":[[2026,5,14]],"date-time":"2026-05-14T17:56:04Z","timestamp":1778781364000},"page":"e1004877","update-policy":"https:\/\/doi.org\/10.1371\/journal.pmed.corrections_policy","source":"Crossref","is-referenced-by-count":1,"title":["Antibody fine specificity correlates with protection from malaria for the RTS,S vaccine in young African children: A post hoc analysis of a phase IIb randomised controlled trial"],"prefix":"10.1371","volume":"23","author":[{"ORCID":"https:\/\/orcid.org\/0009-0000-7114-6283","authenticated-orcid":true,"given":"Alessia","family":"Hysa","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"D. Herbert","family":"Opi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5758-0849","authenticated-orcid":true,"given":"Joshua","family":"Waterhouse","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3987-5229","authenticated-orcid":true,"given":"Sandra","family":"Chishimba","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0077-3885","authenticated-orcid":true,"given":"Jessica L.","family":"Horton","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7109-6757","authenticated-orcid":true,"given":"Natalie","family":"Kingston","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hans J.","family":"Netter","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9584-895X","authenticated-orcid":true,"given":"David","family":"Wetzel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-9184-0454","authenticated-orcid":true,"given":"Michael","family":"Piontek","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3605-038X","authenticated-orcid":true,"given":"Gaoqian","family":"Feng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1059-217X","authenticated-orcid":true,"given":"Jahit","family":"Sacarlal","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6751-4060","authenticated-orcid":true,"given":"Carlota","family":"Doba\u00f1o","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liriye","family":"Kurtovic","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1018-7898","authenticated-orcid":true,"given":"James G.","family":"Beeson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2026,5,14]]},"reference":[{"key":"pmed.1004877.ref001","author":"World Health Organisation","year":"2024"},{"key":"pmed.1004877.ref002","unstructured":"World Health Organisation. Malaria Vaccines (RTS,S and R21) World Health Organisation Questions and Answers WHO Team, Global Malaria Programme 2024 [updated 24 December 2024]. Available from: https:\/\/www.who.int\/news-room\/questions-and-answers\/item\/q-a-on-rts-s-malaria-vaccine"},{"issue":"9988","key":"pmed.1004877.ref003","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1016\/S0140-6736(15)60721-8","article-title":"Efficacy and safety of RTS,S\/AS01 malaria vaccine with or without a booster dose in infants and children in Africa: final results of a phase 3, individually randomised, controlled trial","volume":"386","author":"Rts,S clinical trials partnership","year":"2015","journal-title":"Lancet"},{"issue":"10426","key":"pmed.1004877.ref004","doi-asserted-by":"crossref","first-page":"533","DOI":"10.1016\/S0140-6736(23)02511-4","article-title":"Safety and efficacy of malaria vaccine candidate R21\/Matrix-M in African children: a multicentre, double-blind, randomised, phase 3 trial","volume":"403","author":"MS Datoo","year":"2024","journal-title":"Lancet"},{"issue":"474","key":"pmed.1004877.ref005","doi-asserted-by":"crossref","DOI":"10.1126\/scitranslmed.aau1458","article-title":"Challenges and strategies for developing efficacious and long-lasting malaria vaccines","volume":"11","author":"JG Beeson","year":"2019","journal-title":"Sci Transl Med"},{"key":"pmed.1004877.ref006","doi-asserted-by":"crossref","first-page":"83","DOI":"10.1016\/S0166-6851(02)00216-5","article-title":"A study of genetic diversity in the gene encoding the circumsporozoite protein (CSP) of Plasmodium falciparum from different transmission areas--XVI. Asembo Bay Cohort Project","volume":"125","author":"AA Escalante","year":"2002","journal-title":"Mol Biochem Parasitol"},{"issue":"1","key":"pmed.1004877.ref007","doi-asserted-by":"crossref","first-page":"245","DOI":"10.1186\/s12936-020-03315-4","article-title":"Genetic polymorphism of Plasmodium falciparum circumsporozoite protein on Bioko Island, Equatorial Guinea and global comparative analysis","volume":"19","author":"H-Y Huang","year":"2020","journal-title":"Malar J"},{"issue":"7121","key":"pmed.1004877.ref008","doi-asserted-by":"crossref","first-page":"937","DOI":"10.1038\/nature05361","article-title":"The circumsporozoite protein is an immunodominant protective antigen in irradiated sporozoites","volume":"444","author":"KA Kumar","year":"2006","journal-title":"Nature"},{"issue":"9","key":"pmed.1004877.ref009","doi-asserted-by":"crossref","first-page":"7092","DOI":"10.1074\/jbc.M106862200","article-title":"Binding and invasion of liver cells by Plasmodium falciparum sporozoites. Essential involvement of the amino terminus of circumsporozoite protein","volume":"277","author":"D Rathore","year":"2002","journal-title":"J Biol Chem"},{"issue":"10","key":"pmed.1004877.ref010","doi-asserted-by":"crossref","first-page":"701","DOI":"10.1038\/nrmicro3111","article-title":"Looking under the skin: the first steps in malarial infection and immunity","volume":"11","author":"R M\u00e9nard","year":"2013","journal-title":"Nat Rev Microbiol"},{"issue":"2","key":"pmed.1004877.ref011","doi-asserted-by":"crossref","first-page":"401","DOI":"10.1016\/0092-8674(85)90093-5","article-title":"Circumsporozoite proteins of malaria parasites","volume":"42","author":"V Nussenzweig","year":"1985","journal-title":"Cell"},{"issue":"1","key":"pmed.1004877.ref012","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1084\/jem.20040989","article-title":"The Plasmodium circumsporozoite protein is proteolytically processed during cell invasion","volume":"201","author":"A Coppi","year":"2005","journal-title":"J Exp Med"},{"issue":"1","key":"pmed.1004877.ref013","doi-asserted-by":"crossref","first-page":"53","DOI":"10.1016\/j.molbiopara.2003.09.002","article-title":"The Plasmodium circumsporozoite protein is involved in mosquito salivary gland invasion by sporozoites","volume":"133","author":"JM Myung","year":"2004","journal-title":"Mol Biochem Parasitol"},{"issue":"1","key":"pmed.1004877.ref014","doi-asserted-by":"crossref","first-page":"90","DOI":"10.4161\/hv.6.1.9677","article-title":"From the circumsporozoite protein to the RTS, S\/AS candidate vaccine","volume":"6","author":"J Cohen","year":"2010","journal-title":"Hum Vaccin"},{"issue":"3","key":"pmed.1004877.ref015","doi-asserted-by":"crossref","first-page":"480","DOI":"10.1080\/21645515.2019.1669415","article-title":"RTS,S\/AS01 vaccine (Mosquirix\u2122): an overview","volume":"16","author":"MB Laurens","year":"2020","journal-title":"Hum Vaccin Immunother"},{"issue":"3","key":"pmed.1004877.ref016","doi-asserted-by":"crossref","first-page":"373","DOI":"10.3390\/vaccines8030373","article-title":"Progress in the development of subunit vaccines against malaria","volume":"8","author":"M Skwarczynski","year":"2020","journal-title":"Vaccines (Basel)"},{"key":"pmed.1004877.ref017","doi-asserted-by":"crossref","first-page":"46621","DOI":"10.1038\/srep46621","article-title":"Enhancing protective immunity to malaria with a highly immunogenic virus-like particle vaccine","volume":"7","author":"KA Collins","year":"2017","journal-title":"Sci Rep"},{"issue":"6","key":"pmed.1004877.ref018","doi-asserted-by":"crossref","first-page":"1576","DOI":"10.1093\/infdis\/171.6.1576","article-title":"Safety, immunogenicity, and efficacy of a recombinantly produced Plasmodium falciparum circumsporozoite protein-hepatitis B surface antigen subunit vaccine","volume":"171","author":"DM Gordon","year":"1995","journal-title":"J Infect Dis"},{"issue":"1","key":"pmed.1004877.ref019","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/s12916-019-1277-x","article-title":"Induction and decay of functional complement-fixing antibodies by the RTS, S malaria vaccine in children, and a negative impact of malaria exposure","volume":"17","author":"L Kurtovic","year":"2019","journal-title":"BMC Medicine"},{"key":"pmed.1004877.ref020","doi-asserted-by":"crossref","first-page":"301","DOI":"10.1186\/s12936-016-1348-9","article-title":"The biological function of antibodies induced by the RTS,S\/AS01 malaria vaccine candidate is determined by their fine specificity","volume":"15","author":"S Chaudhury","year":"2016","journal-title":"Malar J"},{"issue":"7","key":"pmed.1004877.ref021","doi-asserted-by":"crossref","first-page":"1128","DOI":"10.1093\/infdis\/jiaa144","article-title":"Multifunctional antibodies are induced by the RTS,S malaria vaccine and associated with protection in a phase 1\/2a trial","volume":"224","author":"L Kurtovic","year":"2021","journal-title":"J Infect Dis"},{"issue":"7","key":"pmed.1004877.ref022","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pone.0020775","article-title":"Protective immunity induced with the RTS,S\/AS vaccine is associated with IL-2 and TNF-\u03b1 producing effector and central memory CD4 T cells","volume":"6","author":"JM Lumsden","year":"2011","journal-title":"PLoS One"},{"issue":"4","key":"pmed.1004877.ref023","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pone.0061395","article-title":"The relationship between RTS,S vaccine-induced antibodies, CD4\u207a T cell responses and protection against Plasmodium falciparum infection","volume":"8","author":"MT White","year":"2013","journal-title":"PLoS One"},{"issue":"12","key":"pmed.1004877.ref024","doi-asserted-by":"crossref","first-page":"1450","DOI":"10.1016\/S1473-3099(15)00239-X","article-title":"Immunogenicity of the RTS,S\/AS01 malaria vaccine and implications for duration of vaccine efficacy: secondary analysis of data from a phase 3 randomised controlled trial","volume":"15","author":"MT White","year":"2015","journal-title":"Lancet Infect Dis"},{"issue":"1","key":"pmed.1004877.ref025","doi-asserted-by":"crossref","first-page":"61","DOI":"10.1186\/s12916-018-1054-2","article-title":"Human antibodies activate complement against Plasmodium falciparum sporozoites, and are associated with protection against malaria in children","volume":"16","author":"L Kurtovic","year":"2018","journal-title":"BMC Med"},{"issue":"1","key":"pmed.1004877.ref026","doi-asserted-by":"crossref","first-page":"1742","DOI":"10.1038\/s41467-021-21998-4","article-title":"Mechanisms and targets of Fc\u03b3-receptor mediated immunity to malaria sporozoites","volume":"12","author":"G Feng","year":"2021","journal-title":"Nat Commun"},{"issue":"553","key":"pmed.1004877.ref027","doi-asserted-by":"crossref","DOI":"10.1126\/scitranslmed.abb4757","article-title":"Mapping functional humoral correlates of protection against malaria challenge following RTS,S\/AS01 vaccination","volume":"12","author":"TJ Suscovich","year":"2020","journal-title":"Sci Transl Med"},{"issue":"1","key":"pmed.1004877.ref028","doi-asserted-by":"crossref","first-page":"289","DOI":"10.1186\/s12916-022-02466-2","article-title":"Induction, decay, and determinants of functional antibodies following vaccination with the RTS,S malaria vaccine in young children","volume":"20","author":"G Feng","year":"2022","journal-title":"BMC Med"},{"issue":"24","key":"pmed.1004877.ref029","doi-asserted-by":"crossref","first-page":"2533","DOI":"10.1056\/NEJMoa0807773","article-title":"Safety and immunogenicity of RTS,S\/AS02D malaria vaccine in infants","volume":"359","author":"S Abdulla","year":"2008","journal-title":"N Engl J Med"},{"issue":"9443","key":"pmed.1004877.ref030","doi-asserted-by":"crossref","first-page":"1411","DOI":"10.1016\/S0140-6736(04)17223-1","article-title":"Efficacy of the RTS,S\/AS02A vaccine against Plasmodium falciparum infection and disease in young African children: randomised controlled trial","volume":"364","author":"PL Alonso","year":"2004","journal-title":"Lancet"},{"issue":"9598","key":"pmed.1004877.ref031","doi-asserted-by":"crossref","first-page":"1543","DOI":"10.1016\/S0140-6736(07)61542-6","article-title":"Safety of the RTS,S\/AS02D candidate malaria vaccine in infants living in a highly endemic area of Mozambique: a double blind randomised controlled phase I\/IIb trial","volume":"370","author":"JJ Aponte","year":"2007","journal-title":"Lancet"},{"issue":"10","key":"pmed.1004877.ref032","doi-asserted-by":"crossref","first-page":"741","DOI":"10.1016\/S1473-3099(11)70100-1","article-title":"Safety and efficacy of the RTS,S\/AS01E candidate malaria vaccine given with expanded-programme-on-immunisation vaccines: 19 month follow-up of a randomised, open-label, phase 2 trial","volume":"11","author":"KP Asante","year":"2011","journal-title":"Lancet Infect Dis"},{"issue":"24","key":"pmed.1004877.ref033","doi-asserted-by":"crossref","first-page":"2521","DOI":"10.1056\/NEJMoa0807381","article-title":"Efficacy of RTS,S\/AS01E vaccine against malaria in children 5 to 17 months of age","volume":"359","author":"P Bejon","year":"2008","journal-title":"N Engl J Med"},{"issue":"1","key":"pmed.1004877.ref034","doi-asserted-by":"crossref","first-page":"2174","DOI":"10.1038\/s41467-019-10195-z","article-title":"Concentration and avidity of antibodies to different circumsporozoite epitopes correlate with RTS,S\/AS01E malaria vaccine efficacy","volume":"10","author":"C Doba\u00f1o","year":"2019","journal-title":"Nat Commun"},{"issue":"4","key":"pmed.1004877.ref035","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pone.0005165","article-title":"Insights into long-lasting protection induced by RTS,S\/AS02A malaria vaccine: further results from a phase IIb trial in Mozambican children","volume":"4","author":"C Guinovart","year":"2009","journal-title":"PLoS One"},{"issue":"10","key":"pmed.1004877.ref036","doi-asserted-by":"crossref","DOI":"10.1016\/S2666-5247(24)00130-7","article-title":"Antibody mechanisms of protection against malaria in RTS, S-vaccinated children: a post-hoc serological analysis of phase 2 trial","volume":"5","author":"L Kurtovic","year":"2024","journal-title":"Lancet Microbe"},{"issue":"2","key":"pmed.1004877.ref037","doi-asserted-by":"crossref","first-page":"102","DOI":"10.1016\/S1473-3099(10)70262-0","article-title":"Efficacy of RTS,S\/AS01E malaria vaccine and exploratory analysis on anti-circumsporozoite antibody titres and protection in children aged 5-17 months in Kenya and Tanzania: a randomised controlled trial","volume":"11","author":"A Olotu","year":"2011","journal-title":"Lancet Infect Dis"},{"issue":"1","key":"pmed.1004877.ref038","doi-asserted-by":"crossref","first-page":"197","DOI":"10.1186\/s12916-018-1186-4","article-title":"Baseline exposure, antibody subclass, and hepatitis B response differentially affect malaria protective immunity following RTS,S\/AS01E vaccination in African children","volume":"16","author":"I Ubillos","year":"2018","journal-title":"BMC Med"},{"issue":"671","key":"pmed.1004877.ref039","doi-asserted-by":"crossref","DOI":"10.1126\/scitranslmed.abo6646","article-title":"The RTS,S malaria vaccine: current impact and foundation for the future","volume":"14","author":"JG Beeson","year":"2022","journal-title":"Sci Transl Med"},{"issue":"48","key":"pmed.1004877.ref040","doi-asserted-by":"crossref","DOI":"10.1073\/pnas.1715812114","article-title":"Structural basis for antibody recognition of the NANP repeats in Plasmodium falciparum circumsporozoite protein","volume":"114","author":"D Oyen","year":"2017","journal-title":"Proc Natl Acad Sci U S A"},{"issue":"7","key":"pmed.1004877.ref041","doi-asserted-by":"crossref","first-page":"1135","DOI":"10.1038\/s41591-020-0881-9","article-title":"Evolution of protective human antibodies against Plasmodium falciparum circumsporozoite protein repeat motifs","volume":"26","author":"R Murugan","year":"2020","journal-title":"Nat Med"},{"issue":"1","key":"pmed.1004877.ref042","doi-asserted-by":"crossref","first-page":"117","DOI":"10.1038\/s41591-023-02659-z","article-title":"A candidate antibody drug for prevention of malaria","volume":"30","author":"KL Williams","year":"2024","journal-title":"Nat Med"},{"issue":"4","key":"pmed.1004877.ref043","doi-asserted-by":"crossref","first-page":"401","DOI":"10.1038\/nm.4513","article-title":"A public antibody lineage that potently inhibits malaria infection through dual binding to the circumsporozoite protein","volume":"24","author":"J Tan","year":"2018","journal-title":"Nat Med"},{"issue":"4","key":"pmed.1004877.ref044","doi-asserted-by":"crossref","first-page":"408","DOI":"10.1038\/nm.4512","article-title":"A human monoclonal antibody prevents malaria infection by targeting a new site of vulnerability on the parasite","volume":"24","author":"NK Kisalu","year":"2018","journal-title":"Nat Med"},{"key":"pmed.1004877.ref045","doi-asserted-by":"crossref","DOI":"10.3389\/fimmu.2021.641421","article-title":"Novel virus-like particle vaccine encoding the circumsporozoite protein of Plasmodium falciparum is immunogenic and induces functional antibody responses in mice","volume":"12","author":"L Kurtovic","year":"2021","journal-title":"Front Immunol"},{"issue":"3","key":"pmed.1004877.ref046","doi-asserted-by":"crossref","first-page":"789","DOI":"10.1128\/IAI.01108-12","article-title":"Full-length Plasmodium falciparum circumsporozoite protein administered with long-chain poly(I\u00b7C) or the Toll-like receptor 4 agonist glucopyranosyl lipid adjuvant-stable emulsion elicits potent antibody and CD4+ T cell immunity and protection in mice","volume":"81","author":"K Kastenm\u00fcller","year":"2013","journal-title":"Infect Immun"},{"issue":"12","key":"pmed.1004877.ref047","doi-asserted-by":"crossref","first-page":"1674","DOI":"10.1016\/j.vaccine.2019.01.056","article-title":"Hepatitis B virus-like particles expressing Plasmodium falciparum epitopes induce complement-fixing antibodies against the circumsporozoite protein","volume":"37","author":"NJ Kingston","year":"2019","journal-title":"Vaccine"},{"issue":"1","key":"pmed.1004877.ref048","doi-asserted-by":"crossref","first-page":"20","DOI":"10.1084\/jem.156.1.20","article-title":"Circumsporozoite proteins of human malaria parasites Plasmodium falciparum and Plasmodium vivax","volume":"156","author":"EH Nardin","year":"1982","journal-title":"J Exp Med"},{"issue":"1","key":"pmed.1004877.ref049","doi-asserted-by":"crossref","first-page":"110","DOI":"10.1038\/s41541-021-00372-x","article-title":"Subclass and avidity of circumsporozoite protein specific antibodies associate with protection status against malaria infection","volume":"6","author":"KE Seaton","year":"2021","journal-title":"NPJ Vaccines"},{"issue":"2","key":"pmed.1004877.ref050","doi-asserted-by":"crossref","DOI":"10.1093\/ofid\/ofaa644","article-title":"Magnitude, specificity, and 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 Infectious Diseases"},{"issue":"10","key":"pmed.1004877.ref051","doi-asserted-by":"crossref","DOI":"10.1084\/jem.20241908","article-title":"Repertoire, function, and structure of serological antibodies induced by the R21\/Matrix-M malaria vaccine","volume":"222","author":"JR McDaniel","year":"2025","journal-title":"J Exp Med"},{"issue":"1","key":"pmed.1004877.ref052","doi-asserted-by":"crossref","first-page":"10","DOI":"10.1038\/s41541-020-00272-6","article-title":"Identification of a neutralizing epitope within minor repeat region of Plasmodium falciparum CS protein","volume":"6","author":"JM Calvo-Calle","year":"2021","journal-title":"NPJ Vaccines"},{"issue":"10","key":"pmed.1004877.ref053","doi-asserted-by":"crossref","DOI":"10.1126\/sciadv.aau8529","article-title":"Cryo-EM structure of P. falciparum circumsporozoite protein with a vaccine-elicited antibody is stabilized by somatically mutated inter-Fab contacts","volume":"4","author":"D Oyen","year":"2018","journal-title":"Sci Adv"},{"issue":"6395","key":"pmed.1004877.ref054","doi-asserted-by":"crossref","first-page":"1358","DOI":"10.1126\/science.aar5304","article-title":"Antihomotypic affinity maturation improves human B cell responses against a repetitive epitope","volume":"360","author":"K Imkeller","year":"2018","journal-title":"Science"},{"issue":"4","key":"pmed.1004877.ref055","doi-asserted-by":"crossref","first-page":"627","DOI":"10.4269\/ajtmh.23-0696","article-title":"Previous malaria exposures and immune dysregulation: developing strategies to improve malaria vaccine efficacy in young children","volume":"110","author":"KR Dobbs","year":"2024","journal-title":"Am J Trop Med Hyg"},{"issue":"48","key":"pmed.1004877.ref056","doi-asserted-by":"crossref","first-page":"7569","DOI":"10.1016\/j.vaccine.2020.09.071","article-title":"Understanding vaccine-elicited protective immunity against pre-erythrocytic stage malaria in endemic regions","volume":"38","author":"AXY Mo","year":"2020","journal-title":"Vaccine"},{"issue":"1","key":"pmed.1004877.ref057","doi-asserted-by":"crossref","first-page":"116","DOI":"10.1038\/s41541-025-01167-0","article-title":"Role of malaria exposure and off-target responses on RTS,S\/AS02A vaccine immunogenicity and protection in Mozambican children","volume":"10","author":"E Fuentes","year":"2025","journal-title":"NPJ Vaccines"},{"issue":"7","key":"pmed.1004877.ref058","doi-asserted-by":"crossref","first-page":"1111","DOI":"10.1093\/infdis\/jiv154","article-title":"Proteolytic cleavage of the Plasmodium falciparum circumsporozoite protein is a target of protective antibodies","volume":"212","author":"DA Espinosa","year":"2015","journal-title":"J Infect Dis"},{"issue":"2","key":"pmed.1004877.ref059","doi-asserted-by":"crossref","first-page":"108996","DOI":"10.1016\/j.celrep.2021.108996","article-title":"Avid binding by B cells to the Plasmodium circumsporozoite protein repeat suppresses responses to protective subdominant epitopes","volume":"35","author":"D Chatterjee","year":"2021","journal-title":"Cell Rep"},{"issue":"1","key":"pmed.1004877.ref060","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1038\/s41541-022-00430-y","article-title":"Restricted valency (NPNA)n repeats and junctional epitope-based circumsporozoite protein vaccines against Plasmodium falciparum","volume":"7","author":"MD Langowski","year":"2022","journal-title":"NPJ Vaccines"},{"issue":"1","key":"pmed.1004877.ref061","doi-asserted-by":"crossref","first-page":"52","DOI":"10.1038\/s41541-023-00653-7","article-title":"Glycosylated nanoparticle-based PfCSP vaccine confers long-lasting antibody responses and sterile protection in mouse malaria model","volume":"8","author":"J Ludwig","year":"2023","journal-title":"NPJ Vaccines"},{"issue":"1","key":"pmed.1004877.ref062","doi-asserted-by":"crossref","first-page":"215","DOI":"10.1038\/s41541-025-01264-0","article-title":"Comparison of major, minor and junctional circumsporozoite protein epitopes for malaria vaccine design","volume":"10","author":"E Ryan","year":"2025","journal-title":"NPJ Vaccines"},{"issue":"1","key":"pmed.1004877.ref063","doi-asserted-by":"crossref","first-page":"225","DOI":"10.1038\/s41541-024-01006-8","article-title":"Probing novel epitopes on the Plasmodium falciparum circumsporozoite protein for vaccine development","volume":"9","author":"PS Krenger","year":"2024","journal-title":"NPJ Vaccines"}],"updated-by":[{"DOI":"10.1371\/journal.pmed.1004877","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2026,5,19]],"date-time":"2026-05-19T00:00:00Z","timestamp":1779148800000}}],"container-title":["PLOS Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pmed.1004877","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,5,19]],"date-time":"2026-05-19T17:41:33Z","timestamp":1779212493000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pmed.1004877"}},"subtitle":[],"editor":[{"given":"Lorenz","family":"von Seidlein","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2026,5,14]]},"references-count":63,"journal-issue":{"issue":"5","published-online":{"date-parts":[[2026,5,14]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.pmed.1004877","relation":{},"ISSN":["1549-1676"],"issn-type":[{"value":"1549-1676","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,5,14]]}}}