{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,2]],"date-time":"2026-10-02T03:40:18Z","timestamp":1790912418057,"version":"4.1.0"},"reference-count":16,"publisher":"F1000 Research Ltd","license":[{"start":{"date-parts":[[2023,10,12]],"date-time":"2023-10-12T00:00:00Z","timestamp":1697068800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100010661","name":"Horizon 2020 Framework Programme","doi-asserted-by":"publisher","award":["RIA2016V-1649-MMVC"],"award-info":[{"award-number":["RIA2016V-1649-MMVC"]}],"id":[{"id":"10.13039\/100010661","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100004440","name":"Wellcome","doi-asserted-by":"publisher","award":["203077"],"award-info":[{"award-number":["203077"]}],"id":[{"id":"10.13039\/100004440","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["wellcomeopenresearch.org"],"crossmark-restriction":false},"short-container-title":["Wellcome Open Res"],"abstract":"<ns3:p>\n                    <ns3:bold>Background:<\/ns3:bold>\n                    Falciparum malaria remains a global health problem. Two vaccines, based on the circumsporozoite antigen, are available.\u00a0 RTS, S\/AS01 was recommended for use in 2021 following the advice of the World Health Organisation (WHO) Strategic Advisory Group of Experts (SAGE) on Immunization and WHO Malaria Policy Advisory Group (MPAG). It has since been pre-qualified in 2022 by the WHO. R21 is similar to RTS, S\/AS01, and recently licensed in Nigeria, Ghana and Burkina Faso following Phase 3 trial results.\n                  <\/ns3:p>\n                  <ns3:p>\n                    <ns3:bold>Methods:<\/ns3:bold>\n                    We conducted a Phase 1b age de-escalation, dose escalation bridging study after a change in the manufacturing process for R21. We recruited healthy adults and children and used a three dose primary vaccination series with a booster dose at 1\u20132 years. Variable doses of R21 and adjuvant (Matrix-M \u2122) were administered at 10\u00b5gR21\/50 \u00b5g Matrix-M\u2122, 5\u00b5gR21\/25\u00b5g Matrix-M\u2122 and 5\u00b5gR21\/50\u00b5g Matrix-M\u2122 to 20 adults, 20 children, and 51 infants.\n                  <\/ns3:p>\n                  <ns3:p>\n                    <ns3:bold>Results:<\/ns3:bold>\n                    Self-limiting adverse events were reported relating to the injection site and mild systemic symptoms. Two serious adverse events were reported, neither linked to vaccination. High levels of IgG antibodies to the circumsporozoite antigen were induced, and geometric mean titres in infants, the target group, were 1.1 (0.9 to 1.3) EU\/mL at day 0, 10175 (7724 to 13404) EU\/mL at day 84 and (following a booster dose at day 421) 6792 (5310 to 8687) EU\/mL at day 456.\n                  <\/ns3:p>\n                  <ns3:p>\n                    <ns3:bold>Conclusions:<\/ns3:bold>\n                    R21\/Matrix-M\u2122 is safe, and immunogenic when given at varied doses with the peak immune response seen in infants 28 days after a three dose primary vaccination series given four weeks apart. Antibody responses were restored 28 days after a 4\n                    <ns3:sup>th<\/ns3:sup>\n                    dose given one year post a three dose primary series in the young children and infants.\n                  <\/ns3:p>\n                  <ns3:p>\n                    <ns3:bold>Registration:<\/ns3:bold>\n                    Clinicaltrials.gov (NCT03580824; 9\n                    <ns3:sup>th<\/ns3:sup>\n                    of July 2018; Pan African Clinical Trials Registry (PACTR202105682956280; 17\n                    <ns3:sup>th<\/ns3:sup>\n                    May 2021).\n                  <\/ns3:p>","DOI":"10.12688\/wellcomeopenres.19795.1","type":"journal-article","created":{"date-parts":[[2023,10,12]],"date-time":"2023-10-12T03:59:49Z","timestamp":1697083189000},"page":"450","update-policy":"https:\/\/doi.org\/10.12688\/wellcomeopenres.crossmark-policy","source":"Crossref","is-referenced-by-count":19,"title":["Safety and immunogenicity of varied doses of R21\/Matrix-M\u2122 vaccine at three years follow-up: A phase 1b age de-escalation, dose-escalation trial in adults, children, and infants in Kilifi-Kenya"],"prefix":"10.12688","volume":"8","author":[{"given":"Samuel","family":"Sang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4968-2842","authenticated-orcid":false,"given":"Mehreen S.","family":"Datoo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8014-7306","authenticated-orcid":false,"given":"Edward","family":"Otieno","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Charles","family":"Muiruri","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3614-0032","authenticated-orcid":false,"given":"Duncan","family":"Bellamy","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emmaloise","family":"Gathuri","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Omar","family":"Ngoto","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Janet","family":"Musembi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sam","family":"Provstgaard-Morys","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lisa","family":"Stockdale","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeremy","family":"Aboagye","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel","family":"Woods","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alison","family":"Lawrie","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Racheal","family":"Roberts","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kelvias","family":"Keter","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6534-5980","authenticated-orcid":false,"given":"Domtila","family":"Kimani","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8977-0030","authenticated-orcid":false,"given":"Francis","family":"Ndungu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0321-7128","authenticated-orcid":false,"given":"Melissa","family":"Kapulu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Irene","family":"Njau","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Benedict","family":"Orindi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katie J.","family":"Ewer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adrian V.S.","family":"Hill","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2135-7549","authenticated-orcid":false,"given":"Philip","family":"Bejon","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0266-1414","authenticated-orcid":false,"given":"Mainga","family":"Hamaluba","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"2560","published-online":{"date-parts":[[2023,10,12]]},"reference":[{"key":"ref-1","first-page":"293","article-title":"World malaria report 2022.","year":"2022"},{"key":"ref-2","doi-asserted-by":"publisher","DOI":"10.1186\/s12936-022-04331-2","article-title":"Malaria in pregnancy control and pregnancy outcomes: a decade's 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Venkatraman","year":"2019","journal-title":"medRxiv."},{"key":"ref-11","doi-asserted-by":"publisher","DOI":"10.1016\/S1473-3099(22)00442-X","article-title":"Efficacy and immunogenicity of R21\/Matrix-M vaccine against clinical malaria after 2 years' follow-up in children in Burkina Faso: a phase 1\/2b randomised controlled trial.","author":"M Datoo","year":"2022","journal-title":"Lancet Infect Dis."},{"key":"ref-12","doi-asserted-by":"publisher","first-page":"1809-18","DOI":"10.1016\/S0140-6736(21)00943-0","article-title":"Efficacy of a low-dose candidate malaria vaccine, R21 in adjuvant Matrix-M, with seasonal administration to children in Burkina Faso: a randomised controlled trial.","volume":"397","author":"M Datoo","year":"2021","journal-title":"Lancet."},{"key":"ref-13","doi-asserted-by":"publisher","first-page":"650-7","DOI":"10.1093\/ije\/dys062","article-title":"Profile: The Kilifi Health and Demographic Surveillance System (KHDSS).","volume":"41","author":"J 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Status and perspectives].","volume":"165","author":"E Englev","year":"2003","journal-title":"Ugeskr Laeger."},{"key":"ref-15","article-title":"KWTRP Harvard Dataverse repository.","author":"L Mwango","year":"2023"},{"key":"ref-16","doi-asserted-by":"publisher","DOI":"10.1038\/s41541-018-0084-2","article-title":"Safety and efficacy of novel malaria vaccine regimens of RTS,S\/AS01B alone, or with concomitant ChAd63-MVA-vectored vaccines expressing ME-TRAP.","volume":"3","author":"T Rampling","year":"2018","journal-title":"NPJ Vaccines."}],"container-title":["Wellcome Open Research"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/wellcomeopenresearch.org\/articles\/8-450\/v1\/xml","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/wellcomeopenresearch.org\/articles\/8-450\/v1\/pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/wellcomeopenresearch.org\/articles\/8-450\/v1\/iparadigms","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,5,28]],"date-time":"2024-05-28T01:35:08Z","timestamp":1716860108000},"score":1,"resource":{"primary":{"URL":"https:\/\/wellcomeopenresearch.org\/articles\/8-450\/v1"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,10,12]]},"references-count":16,"URL":"https:\/\/doi.org\/10.12688\/wellcomeopenres.19795.1","relation":{"has-review":[{"id-type":"doi","id":"10.21956\/wellcomeopenres.21926.r81710","asserted-by":"subject"},{"id-type":"doi","id":"10.21956\/wellcomeopenres.21926.r81717","asserted-by":"subject"},{"id-type":"doi","id":"10.21956\/wellcomeopenres.21926.r81710","asserted-by":"object"},{"id-type":"doi","id":"10.21956\/wellcomeopenres.21926.r81717","asserted-by":"object"}]},"ISSN":["2398-502X"],"issn-type":[{"value":"2398-502X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,10,12]]},"assertion":[{"value":"Indexed","URL":"https:\/\/wellcomeopenresearch.org\/articles\/8-450\/v1#article-reports","order":0,"name":"referee-status","label":"Referee status","group":{"name":"current-referee-status","label":"Current Referee Status"}},{"value":"10.21956\/wellcomeopenres.21926.r81710, George Ayodo, Jaramogi Oginga Odinga University of Science and Technology, Bondo, Siaya, 24 May 2024, version 1, indexed","URL":"https:\/\/wellcomeopenresearch.org\/articles\/8-450\/v1#referee-response-81710","order":0,"name":"referee-response-81710","label":"Referee Report","group":{"name":"article-reports","label":"Article Reports"}},{"value":"10.21956\/wellcomeopenres.21926.r81717, Irene S Soares, Department of Clinical and Toxicological Analyses, School of Pharmaceutical Sciences, University of S\u00e3o Paulo, S\u00e3o Paulo, 28 May 2024, version 1, indexed","URL":"https:\/\/wellcomeopenresearch.org\/articles\/8-450\/v1#referee-response-81717","order":1,"name":"referee-response-81717","label":"Referee Report","group":{"name":"article-reports","label":"Article Reports"}},{"value":"This work was supported by Wellcome [203077]. This publication was produced by the Multi-Stage Malaria Vaccine Consortium; MMVC which is part of the EDCTP2 programme supported by the European Union [RIA2016V-1649-MMVC]. The views and opinions of authors expressed herein do not necessarily state or reflect those of EDCTP. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.","order":2,"name":"grant-information","label":"Grant Information"},{"value":"This is an open access article distributed under the terms of the Creative Commons Attribution Licence, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.","order":0,"name":"copyright-info","label":"Copyright"}]}}