{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,22]],"date-time":"2026-10-22T03:44:59Z","timestamp":1792640699132,"version":"4.5.0"},"reference-count":42,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2024,5,28]],"date-time":"2024-05-28T00:00:00Z","timestamp":1716854400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:sec><jats:title>Background<\/jats:title><jats:p>Despite decades of effort, <jats:italic>Plasmodium falciparum<\/jats:italic> malaria remains a leading killer of children. The absence of a highly effective vaccine and the emergence of parasites resistant to both diagnosis as well as treatment hamper effective public health interventions.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods and results<\/jats:title><jats:p>To discover new vaccine candidates, we used our whole proteome differential screening method and identified PfGBP130 as a parasite protein uniquely recognized by antibodies from children who had developed resistance to <jats:italic>P. falciparum<\/jats:italic> infection but not from those who remained susceptible. We formulated PfGBP130 as lipid encapsulated mRNA, DNA plasmid, and recombinant protein-based immunogens and evaluated the efficacy of murine polyclonal anti-PfGBP130 antisera to inhibit parasite growth in vitro. Immunization of mice with PfGBP130-A (aa 111\u2013374), the region identified in our differential screen, formulated as a DNA plasmid or lipid encapsulated mRNA, but not as a recombinant protein, induced antibodies that inhibited RBC invasion <jats:italic>in vitro<\/jats:italic>. mRNA encoding the full ectodomain of PfGBP130 (aa 89\u2013824) also generated parasite growth-inhibitory antibodies.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>We are currently advancing PfGBP130-A formulated as a lipid-encapsulated mRNA for efficacy evaluation in non-human primates.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fimmu.2024.1350560","type":"journal-article","created":{"date-parts":[[2024,5,28]],"date-time":"2024-05-28T04:58:20Z","timestamp":1716872300000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":4,"title":["Immunization with PfGBP130 generates antibodies that inhibit RBC invasion by P. falciparum parasites"],"prefix":"10.3389","volume":"15","author":[{"given":"Yannick","family":"Johnson","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ahmad Rushdi","family":"Shakri","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sunthorn","family":"Pond-Tor","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anup","family":"Jnawali","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tanbir","family":"Najrana","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haiwei","family":"Wu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jhasketan","family":"Badhai","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mohamad-Gabriel","family":"Alameh","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Drew","family":"Weissman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Edward","family":"Kabyemela","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patrick","family":"Duffy","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michal","family":"Fried","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jonathan","family":"Kurtis","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dipak Kumar","family":"Raj","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2024,5,28]]},"reference":[{"key":"B1","volume-title":"The world malaria report 2021","year":"2021"},{"key":"B2","doi-asserted-by":"publisher","first-page":"48","DOI":"10.1038\/s41541-020-0196-3","article-title":"Malaria vaccines since 2000: Progress, priorities, products","volume":"5","author":"Duffy","year":"2020","journal-title":"NPJ Vaccines"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMp058217","article-title":"Betting on a malaria vaccine","volume":"353","author":"Okie","year":"2005","journal-title":"N Engl J Med"},{"key":"B4","doi-asserted-by":"publisher","first-page":"17","DOI":"10.1080\/21645515.2017.1381809","article-title":"Characterization of t-cell immune responses in clinical trials of the candidate RTS, S malaria vaccine","volume":"14","author":"Moris","year":"2018","journal-title":"Hum Vaccin Immunother"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1111\/j.1462-5822.2006.00861.x","article-title":"Plasmodium sporozoites trickle out of the injection site","volume":"9","author":"Yamauchi","year":"2007","journal-title":"Cell Microbiol"},{"key":"B6","doi-asserted-by":"publisher","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":"White","year":"2015","journal-title":"Lancet Infect Dis"},{"key":"B7","doi-asserted-by":"publisher","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","year":"2015","journal-title":"Lancet"},{"key":"B8","doi-asserted-by":"publisher","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":"Datoo","year":"2021","journal-title":"Lancet"},{"key":"B9","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\u2019 follow-up in children in Burkina Faso: A phase 1\/2b randomised controlled trial","volume":"22","author":"Datoo","year":"2022","journal-title":"Lancet Infect Dis"},{"key":"B10","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":"B11","doi-asserted-by":"publisher","DOI":"10.3347\/kjp.2014.52.1.105","article-title":"Evolution of genetic polymorphisms of plasmodium falciparum merozoite surface protein (PfMSP) in Thailand","volume":"52","author":"Kuesap","year":"2014","journal-title":"Korean J Parasitol"},{"key":"B12","doi-asserted-by":"publisher","first-page":"000350","DOI":"10.1099\/acmi.0.000350","article-title":"Genetic polymorphism of Plasmodium falciparum msp-1, msp-2 and glurp vaccine candidate genes in pre-artemisinin era clinical isolates from lakhimpur district in assam, northeast India","volume":"4","author":"Sathishkumar","year":"2022","journal-title":"Access Microbiol"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.1016\/j.meegid.2006.01.009","article-title":"Genetic diversity in the block 2 region of the merozoite surface protein 1 (MSP-1) of Plasmodium falciparum: Additional complexity and selection and convergence in fragment size polymorphism","volume":"6","author":"Takala","year":"2006","journal-title":"Infect Genet Evol"},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0004708","article-title":"Blood stage malaria vaccine eliciting high antigen-specific antibody concentrations confers no protection to young children in western Kenya","volume":"4","author":"Ogutu","year":"2009","journal-title":"PloS One"},{"key":"B15","doi-asserted-by":"publisher","first-page":"6","DOI":"10.1186\/s12936-019-3096-0","article-title":"Genetic polymorphisms in malaria vaccine candidate Plasmodium falciparum reticulocyte-binding protein homologue-5 among populations in lagos, Nigeria","volume":"19","author":"Ajibaye","year":"2020","journal-title":"Malaria J"},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.3389\/fitd.2023.1102265","article-title":"Limited genetic variations of the Rh5-CyRPA-Ripr invasion complex in Plasmodium falciparum parasite population in selected malaria-endemic regions, Kenya","volume":"4","author":"Waweru","year":"2023","journal-title":"Front Trop Dis"},{"key":"B17","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijpara.2008.10.006","article-title":"Reticulocyte-binding protein homologue 5 - an essential adhesin involved in invasion of human erythrocytes by plasmodium falciparum","volume":"39","author":"Baum","year":"2009","journal-title":"Int J Parasitol"},{"key":"B18","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.83681","article-title":"Erythrocyte invasion-neutralising antibodies prevent Plasmodium falciparum rh5 from binding to basigin-containing membrane protein complexes","volume":"12","author":"Jamwal","year":"2023","journal-title":"eLife"},{"key":"B19","doi-asserted-by":"publisher","DOI":"10.1016\/j.chom.2014.11.017","article-title":"A PfRH5-based vaccine is efficacious against heterologous strain blood-stage Plasmodium falciparum infection in Aotus monkeys","volume":"17","author":"Douglas","year":"2015","journal-title":"Cell Host Microbe"},{"key":"B20","doi-asserted-by":"publisher","first-page":"701","DOI":"10.1016\/j.medj.2021.03.014","article-title":"Reduced blood-stage malaria growth and immune correlates in humans following rh5 vaccination","volume":"2","author":"Minassian","year":"2021","journal-title":"Med"},{"key":"B21","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-020-2220-1","article-title":"Anti-PfGARP activates programmed cell death of parasites and reduces severe malaria","volume":"582","author":"Raj","year":"2020","journal-title":"Nature"},{"key":"B22","doi-asserted-by":"publisher","DOI":"10.1126\/science.1254417","article-title":"Antibodies to PfSEA-1 block parasite egress from rbcs and protect against malaria infection","volume":"344","author":"Raj","year":"2014","journal-title":"Science"},{"key":"B23","doi-asserted-by":"publisher","DOI":"10.1086\/432550","article-title":"Antibodies to rhoptry-associated membrane antigen predict resistance to plasmodium falciparum","volume":"192","author":"Nixon","year":"2005","journal-title":"J Infect Dis"},{"key":"B24","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pmed.0020407","article-title":"Maternal malaria and gravidity interact to modify infant susceptibility to malaria","volume":"2","author":"Mutabingwa","year":"2005","journal-title":"PloS Med"},{"key":"B25","doi-asserted-by":"publisher","DOI":"10.1086\/589512","article-title":"Decreased susceptibility to plasmodium falciparum infection in pregnant women with iron deficiency","volume":"198","author":"Kabyemela","year":"2008","journal-title":"J Infect Dis"},{"key":"B26","doi-asserted-by":"publisher","DOI":"10.1107\/S0907444906029799","article-title":"A time- and cost-efficient system for high-level protein production in mammalian cells","volume":"62","author":"Aricescu","year":"2006","journal-title":"Acta Crystallogr D Biol Crystallogr"},{"key":"B27","doi-asserted-by":"publisher","first-page":"29","DOI":"10.1007\/978-1-62703-260-5_2","article-title":"In vitro transcription of long rna containing modified nucleosides","volume":"969","author":"Pardi","year":"2013","journal-title":"Methods Mol Biol"},{"key":"B28","doi-asserted-by":"publisher","DOI":"10.1038\/mt.2015.103","article-title":"Sequence-engineered mrna without chemical nucleoside modifications enables an effective protein therapy in large animals","volume":"23","author":"Thess","year":"2015","journal-title":"Mol Ther"},{"key":"B29","doi-asserted-by":"publisher","DOI":"10.1126\/science.781840","article-title":"Human malaria parasites in continuous culture","volume":"193","author":"Trager","year":"1976","journal-title":"Science"},{"key":"B30","doi-asserted-by":"publisher","first-page":"108","DOI":"10.1186\/1475-2875-7-108","article-title":"A semi-automated multiplex high-throughput assay for measuring igg antibodies against plasmodium falciparum erythrocyte membrane protein 1 (PfEMP1) domains in small volumes of plasma","volume":"7","author":"Cham","year":"2008","journal-title":"Malar J"},{"key":"B31","doi-asserted-by":"publisher","first-page":"9","DOI":"10.1093\/infdis\/jir222","article-title":"Effect of the pre-erythrocytic candidate malaria vaccine RTS, S\/AS01e on blood stage immunity in young children","volume":"204","author":"Bejon","year":"2011","journal-title":"J Infect Dis"},{"key":"B32","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.73.6.3677-3685.2005","article-title":"Phase 1 clinical trial of apical membrane antigen 1: An asexual blood-stage vaccine for plasmodium falciparum malaria","volume":"73","author":"Malkin","year":"2005","journal-title":"Infect Immun"},{"key":"B33","unstructured":"Growth inhibition assay procedure\n            LongC\n          2013"},{"key":"B34","doi-asserted-by":"publisher","DOI":"10.1016\/0014-4894(88)90107-5","article-title":"Stage-dependent processing and localization of a Plasmodium falciparum protein of 130,000 molecular weight","volume":"65","author":"Perkins","year":"1988","journal-title":"Exp Parasitol"},{"key":"B35","doi-asserted-by":"publisher","DOI":"10.1084\/jem.160.3.788","article-title":"Surface proteins of Plasmodium falciparum merozoites binding to the erythrocyte receptor, glycophorin","volume":"160","author":"Perkins","year":"1984","journal-title":"J Exp Med"},{"key":"B36","doi-asserted-by":"publisher","DOI":"10.1084\/jem.166.2.376","article-title":"Possible pitfalls in the identification of glycophorin-binding proteins of Plasmodium falciparum","volume":"166","author":"van Schravendijk","year":"1987","journal-title":"J Exp Med"},{"key":"B37","doi-asserted-by":"publisher","DOI":"10.1016\/0092-8674(86)90834-2","article-title":"A tandemly repeated sequence determines the binding domain for an erythrocyte receptor binding protein of P. falciparum","volume":"44","author":"Kochan","year":"1986","journal-title":"Cell"},{"key":"B38","doi-asserted-by":"publisher","first-page":"77","DOI":"10.1016\/0166-6851(89)90203-X","article-title":"Specificities of antibodies that inhibit merozoite dispersal from malaria-infected erythrocytes","volume":"36","author":"Lyon","year":"1989","journal-title":"Mol Biochem Parasitol"},{"key":"B39","doi-asserted-by":"publisher","first-page":"495","DOI":"10.1590\/S0074-02762000000400009","article-title":"A GBP 130 derived peptide from Plasmodium falciparum binds to human erythrocytes and inhibits merozoite invasion in vitro","volume":"95","author":"Suarez","year":"2000","journal-title":"Mem Inst Oswaldo Cruz"},{"key":"B40","doi-asserted-by":"publisher","DOI":"10.1038\/s41573-021-00283-5","article-title":"Mrna vaccines for infectious diseases: Principles, delivery and clinical translation","volume":"20","author":"Chaudhary","year":"2021","journal-title":"Nat Rev Drug Discovery"},{"key":"B41","doi-asserted-by":"publisher","DOI":"10.1126\/science.3883491","article-title":"Isolation of the gene for a glycophorin-binding protein implicated in erythrocyte invasion by a malaria parasite","volume":"227","author":"Ravetch","year":"1985","journal-title":"Science"},{"key":"B42","doi-asserted-by":"publisher","DOI":"10.4269\/ajtmh.1991.45.548","article-title":"Immunization of owl monkeys with a recombinant protein containing repeated epitopes of a plasmodium falciparum glycophorin-binding protein","volume":"45","author":"Aronson","year":"1991","journal-title":"Am J Trop Med Hyg"}],"container-title":["Frontiers in Immunology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2024.1350560\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,5,28]],"date-time":"2024-05-28T04:58:26Z","timestamp":1716872306000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2024.1350560\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,5,28]]},"references-count":42,"alternative-id":["10.3389\/fimmu.2024.1350560"],"URL":"https:\/\/doi.org\/10.3389\/fimmu.2024.1350560","relation":{},"ISSN":["1664-3224"],"issn-type":[{"value":"1664-3224","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,5,28]]},"article-number":"1350560"}}