{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,13]],"date-time":"2026-06-13T03:48:50Z","timestamp":1781322530294,"version":"3.54.1"},"reference-count":20,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,1,27]],"date-time":"2026-01-27T00:00:00Z","timestamp":1769472000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["JP24K02273 , JP20KK0379"],"award-info":[{"award-number":["JP24K02273 , JP20KK0379"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>\n                      The\n                      <jats:italic>Plasmodium falciparum<\/jats:italic>\n                      Rh5-interacting protein (PfRipr) is a key component of the pentameric PTRAMP-CSS-PfRipr-CyRPA-RH5 (PCRCR) complex, which is essential for erythrocyte invasion. Antibodies against PfRipr can inhibit parasite growth, but the full-length protein is structurally complex and challenging to produce as a recombinant antigen. We previously found that a specific PfRipr fragment, PfRipr5, was the most potent antigen; however, identifying minimal functional regions within PfRipr5 is critical for improving the vaccine design.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We investigated PfRipr5, a truncated fragment of PfRipr consisting of EGF-like domains 5\u20139, and identified the epitope recognized by the growth-inhibitory monoclonal antibody 29B11. Epitope characterization was conducted using Western blotting with cysteine-substituted mutants and surface plasmon resonance (SPR) analysis with a single-site kinetics model.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results and conclusion<\/jats:title>\n                    <jats:p>The identified 20-amino-acid region represents a cysteine-associated epitope recognized by the growth-inhibitory monoclonal antibody 29B11. This study defines a growth-inhibitory epitope within PfRipr5 whose recognition is associated with cysteine integrity. These findings provide a tractable molecular entry point for dissecting PfRipr function and support epitope-focused strategies for rational design of subunit vaccines against blood-stage malaria.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fimmu.2026.1724796","type":"journal-article","created":{"date-parts":[[2026,1,27]],"date-time":"2026-01-27T06:40:01Z","timestamp":1769496001000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":2,"title":["Identification of a growth-inhibitory epitope in PfRipr5, a malaria vaccine candidate against Plasmodium falciparum"],"prefix":"10.3389","volume":"17","author":[{"given":"Hikaru","family":"Nagaoka","sequence":"first","affiliation":[{"name":"Division of Malaria Research, Proteo-Science Center, Ehime University","place":["Matsuyama, Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Akihisa","family":"Fukushima","sequence":"additional","affiliation":[{"name":"Vaccines, Sumitomo Pharma","place":["Osaka, Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takafumi","family":"Tsuboi","sequence":"additional","affiliation":[{"name":"Division of Cell-Free Sciences, Proteo-Science Center, Ehime University","place":["Matsuyama, Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eizo","family":"Takashima","sequence":"additional","affiliation":[{"name":"Division of Malaria Research, Proteo-Science Center, Ehime University","place":["Matsuyama, Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,1,27]]},"reference":[{"key":"B1","volume-title":"World malaria report 2024: Addressing inequity in the global malaria response","year":"2024"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1586\/14760584.2016.1141680","article-title":"Progress and prospects for blood-stage malaria vaccines","volume":"15","author":"Miura","year":"2016","journal-title":"Expert Rev Vaccines"},{"key":"B3","doi-asserted-by":"publisher","first-page":"43","DOI":"10.1016\/j.chom.2018.06.008","article-title":"Malaria vaccines: recent advances and new horizons","volume":"24","author":"Draper","year":"2018","journal-title":"Cell Host Microbe"},{"key":"B4","doi-asserted-by":"publisher","first-page":"100","DOI":"10.3390\/biom14010100","article-title":"The need for novel asexual blood-stage malaria vaccine candidates for plasmodium falciparum","volume":"14","author":"Takashima","year":"2024","journal-title":"Biomolecules"},{"key":"B5","doi-asserted-by":"publisher","first-page":"495","DOI":"10.1016\/S1473-3099(24)00752-7","article-title":"Safety and efficacy of the blood-stage malaria vaccine RH5.1\/Matrix-M in Burkina Faso: interim results of a double-blind, randomised, controlled, phase 2b trial in children","volume":"25","author":"Natama","year":"2025","journal-title":"Lancet Infect Dis"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1038\/s41564-022-01261-2","article-title":"PCRCR complex is essential for invasion of human erythrocytes by Plasmodium falciparum","volume":"7","author":"Scally","year":"2022","journal-title":"Nat Microbiol"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1002199","article-title":"An EGF-like protein forms a complex with PfRh5 and is required for invasion of human erythrocytes by Plasmodium falciparum","volume":"7","author":"Chen","year":"2011","journal-title":"PLoS Pathog"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1016\/j.vaccine.2016.09.028","article-title":"Identification of Plasmodium falciparum reticulocyte binding protein homologue 5-interacting protein, PfRipr, as a highly conserved blood-stage malaria vaccine candidate","volume":"34","author":"Ntege","year":"2016","journal-title":"Vaccine"},{"key":"B9","doi-asserted-by":"publisher","first-page":"6573","DOI":"10.1038\/s41598-020-63611-6","article-title":"Antibodies against a short region of PfRipr inhibit Plasmodium falciparum merozoite invasion and PfRipr interaction with Rh5 and SEMA7A","volume":"10","author":"Nagaoka","year":"2020","journal-title":"Sci Rep"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.1016\/j.pt.2020.04.003","article-title":"The RH5-cyRPA-ripr complex as a malaria vaccine target","volume":"36","author":"Ragotte","year":"2020","journal-title":"Trends Parasitol"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2022.1002430","article-title":"A novel asexual blood-stage malaria vaccine candidate: PfRipr5 formulated with human-use adjuvants induces potent growth inhibitory antibodies","volume":"13","author":"Takashima","year":"2022","journal-title":"Front Immunol"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.3389\/fbioe.2022.908509","article-title":"Asexual blood-stage malaria vaccine candidate pfRipr5: enhanced production in insect cells","volume":"10","author":"Correia","year":"2022","journal-title":"Front Bioeng Biotechnol"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.1111\/cmi.13030","article-title":"Neutralising antibodies block the function of Rh5\/Ripr\/CyRPA complex during invasion of Plasmodium falciparum into human erythrocytes","volume":"21","author":"Healer","year":"2019","journal-title":"Cell Microbiol"},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-023-06856-1","article-title":"The PfRCR complex bridges malaria parasite and erythrocyte during invasion","volume":"625","author":"Farrell","year":"2024","journal-title":"Nature"},{"key":"B15","doi-asserted-by":"publisher","first-page":"4857","DOI":"10.1038\/s41467-024-48721-3","article-title":"Development of an improved blood-stage malaria vaccine targeting the essential RH5-CyRPA-RIPR invasion complex","volume":"15","author":"Williams","year":"2024","journal-title":"Nat Commun"},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.1101\/2025.09.23.25335263","article-title":"Genetic diversity of the malaria vaccine candidate pfRIPR in a high transmission region of Senegal","author":"Nair","year":"2025","journal-title":"medRxiv"},{"key":"B17","doi-asserted-by":"publisher","DOI":"10.1038\/nchem.2236","article-title":"Functionalization of cobalt porphyrin-phospholipid bilayers with his-tagged ligands and antigens","volume":"7","author":"Shao","year":"2015","journal-title":"Nat Chem"},{"key":"B18","doi-asserted-by":"publisher","first-page":"773","DOI":"10.1038\/s42003-022-03688-z","article-title":"Vaccine co-display of CSP and Pfs230 on liposomes targeting two Plasmodium falciparum differentiation stages","volume":"5","author":"Huang","year":"2022","journal-title":"Commun Biol"},{"key":"B19","doi-asserted-by":"publisher","first-page":"4","DOI":"10.1038\/s41541-021-00423-3","article-title":"Elucidating functional epitopes within the N-terminal region of malaria transmission blocking vaccine antigen Pfs230","volume":"7","author":"Miura","year":"2022","journal-title":"NPJ Vaccines"},{"key":"B20","doi-asserted-by":"publisher","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":"Datoo","year":"2024","journal-title":"Lancet"}],"container-title":["Frontiers in Immunology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2026.1724796\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,1,27]],"date-time":"2026-01-27T06:40:03Z","timestamp":1769496003000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2026.1724796\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,1,27]]},"references-count":20,"alternative-id":["10.3389\/fimmu.2026.1724796"],"URL":"https:\/\/doi.org\/10.3389\/fimmu.2026.1724796","relation":{},"ISSN":["1664-3224"],"issn-type":[{"value":"1664-3224","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,1,27]]},"article-number":"1724796"}}