{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,17]],"date-time":"2026-08-17T18:27:51Z","timestamp":1786991271282,"version":"build-2736575974"},"update-to":[{"DOI":"10.1371\/journal.ppat.1014493","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2026,8,17]],"date-time":"2026-08-17T00:00:00Z","timestamp":1786924800000}}],"reference-count":50,"publisher":"Public Library of Science (PLoS)","issue":"8","license":[{"start":{"date-parts":[[2026,8,10]],"date-time":"2026-08-10T00:00:00Z","timestamp":1786320000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/publicdomain\/zero\/1.0\/"}],"funder":[{"DOI":"10.13039\/100006492","name":"Division of Intramural Research, National Institute of Allergy and Infectious Diseases","doi-asserted-by":"publisher","award":["#R01-AI125421-01A1"],"award-info":[{"award-number":["#R01-AI125421-01A1"]}],"id":[{"id":"10.13039\/100006492","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100006492","name":"Division of Intramural Research, National Institute of Allergy and Infectious Diseases","doi-asserted-by":"publisher","award":["#1RO1AI141229"],"award-info":[{"award-number":["#1RO1AI141229"]}],"id":[{"id":"10.13039\/100006492","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001804","name":"Canada Research Chairs Program","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100001804","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["www.plospathogens.org"],"crossmark-restriction":false},"short-container-title":["PLoS Pathog"],"abstract":"<jats:p>\n                    Transferrin binding protein B (TbpB), an iron acquisition protein, has long been recognized as a promising vaccine candidate targeting the pathogenic Neisseria species, including\n                    <jats:italic>Neisseria meningitidis<\/jats:italic>\n                    , the cause of meningococcal disease, and\n                    <jats:italic>Neisseria gonorrhoeae<\/jats:italic>\n                    , the cause of gonorrhea. A challenge to the development of this protein as a vaccine immunogen is the extent of antigenic variability it exhibits, which complicates the selection of a single variant to elicit a broadly cross-protective immune response. We have utilized structure-informed antigen engineering to develop a minimized version of TbpB consisting of the protein\u2019s carboxy-terminal lobe with its variable surface loops removed. Here, we reveal the effectiveness of this \u201cloopless C-lobe\u201d as an independent immunogen, with structural characterization and stability studies to demonstrate its integrity, and murine immunization and challenge studies that establish its ability to elicit robust protective efficacy by using models of\n                    <jats:italic>N. meningitidis<\/jats:italic>\n                    invasive infection and nasopharyngeal colonization. The breadth of protection provided, as measured by both in vitro analysis and cross-protection mouse challenge studies, indicate that a single loopless C-lobe elicits a broadly cross-protective immune response against the diverse panel of meningococcal strains tested, and that the cross-reactivity is superior to that offered by the intact TbpB or the native C-lobe. Together, this study demonstrates the utility of structure-informed antigen engineering towards the development of broadly efficacious protein-based vaccines.\n                  <\/jats:p>","DOI":"10.1371\/journal.ppat.1014493","type":"journal-article","created":{"date-parts":[[2026,8,10]],"date-time":"2026-08-10T17:38:52Z","timestamp":1786383532000},"page":"e1014493","update-policy":"https:\/\/doi.org\/10.1371\/journal.ppat.corrections_policy","source":"Crossref","is-referenced-by-count":0,"title":["Rationally designed minimized TbpB confers broad protection against meningococcal infection"],"prefix":"10.1371","volume":"22","author":[{"given":"Epshita A.","family":"Islam","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jamie E.","family":"Fegan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gregory B.","family":"Cole","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Charles","family":"Calmettes","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dixon","family":"Ng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Natalie Y. T.","family":"Au","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carolyn","family":"Marion","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sang K.","family":"Ahn","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David M.","family":"Curran","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laura-lee","family":"Caruso","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anthony B.","family":"Schryvers","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Trevor F.","family":"Moraes","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1477-3616","authenticated-orcid":true,"given":"Scott D.","family":"Gray-Owen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2026,8,10]]},"reference":[{"key":"ppat.1014493.ref001","doi-asserted-by":"crossref","first-page":"2405","DOI":"10.3389\/fimmu.2018.02405","article-title":"Intranasal Vaccination With Lipoproteins Confers Protection Against Pneumococcal Colonisation","volume":"9","author":"F Vo\u00df","year":"2018","journal-title":"Front Immunol"},{"issue":"4","key":"ppat.1014493.ref002","doi-asserted-by":"crossref","first-page":"209","DOI":"10.1056\/NEJM199807233390401","article-title":"Vaccination against Lyme disease with recombinant Borrelia burgdorferi outer-surface lipoprotein A with adjuvant. Lyme Disease Vaccine Study Group","volume":"339","author":"AC Steere","year":"1998","journal-title":"N Engl J Med"},{"issue":"6","key":"ppat.1014493.ref003","doi-asserted-by":"crossref","first-page":"841","DOI":"10.1586\/14760584.2015.1016915","article-title":"Neisseria meningitidis factor H-binding protein fHbp: a key virulence factor and vaccine antigen","volume":"14","author":"KL Seib","year":"2015","journal-title":"Expert Rev Vaccines"},{"issue":"1","key":"ppat.1014493.ref004","doi-asserted-by":"crossref","first-page":"55","DOI":"10.1128\/iai.65.1.55-63.1997","article-title":"Evaluation of recombinant transferrin-binding protein B variants from Neisseria meningitidis for their ability to induce cross-reactive and bactericidal antibodies against a genetically diverse collection of serogroup B strains","volume":"65","author":"B Rokbi","year":"1997","journal-title":"Infect Immun"},{"issue":"3","key":"ppat.1014493.ref005","doi-asserted-by":"crossref","first-page":"884","DOI":"10.1128\/iai.63.3.884-890.1995","article-title":"Evaluation of transferrin-binding protein 2 within the transferrin-binding protein complex as a potential antigen for future meningococcal vaccines","volume":"63","author":"L Lissolo","year":"1995","journal-title":"Infect Immun"},{"issue":"7","key":"ppat.1014493.ref006","doi-asserted-by":"crossref","first-page":"3945","DOI":"10.1128\/IAI.73.7.3945-3953.2005","article-title":"Intranasal administration of recombinant Neisseria gonorrhoeae transferrin binding proteins A and B conjugated to the cholera toxin B subunit induces systemic and vaginal antibodies in mice","volume":"73","author":"GA Price","year":"2005","journal-title":"Infect Immun"},{"issue":"2","key":"ppat.1014493.ref007","doi-asserted-by":"crossref","DOI":"10.1093\/femspd\/ftx010","article-title":"Neisserial surface lipoproteins: structure, function and biogenesis","volume":"75","author":"Y Hooda","year":"2017","journal-title":"Pathog Dis"},{"issue":"3","key":"ppat.1014493.ref008","doi-asserted-by":"crossref","first-page":"491","DOI":"10.1002\/mbo3.254","article-title":"Patterns of structural and sequence variation within isotype lineages of the Neisseria meningitidis transferrin receptor system","volume":"4","author":"P Adamiak","year":"2015","journal-title":"Microbiologyopen"},{"issue":"6","key":"ppat.1014493.ref009","doi-asserted-by":"crossref","first-page":"548","DOI":"10.1080\/00325481.2016.1203238","article-title":"Characteristics of a new meningococcal serogroup B vaccine, bivalent rLP2086 (MenB-FHbp; Trumenba\u00ae)","volume":"128","author":"A Gandhi","year":"2016","journal-title":"Postgrad Med"},{"key":"ppat.1014493.ref010","article-title":"The new multicomponent vaccine against meningococcal serogroup B, 4CMenB: immunological, functional and structural characterization of the antigens","author":"D Serruto","year":"2012","journal-title":"Vaccine"},{"issue":"3","key":"ppat.1014493.ref011","doi-asserted-by":"crossref","first-page":"314","DOI":"10.1080\/10409238.2017.1293606","article-title":"Iron acquisition through the bacterial transferrin receptor","volume":"52","author":"AK Pogoutse","year":"2017","journal-title":"Crit Rev Biochem Mol Biol"},{"issue":"5","key":"ppat.1014493.ref012","doi-asserted-by":"crossref","DOI":"10.1371\/journal.ppat.1002027","article-title":"Transcriptome analysis of Neisseria meningitidis in human whole blood and mutagenesis studies identify virulence factors involved in blood survival","volume":"7","author":"H Echenique-Rivera","year":"2011","journal-title":"PLoS Pathog"},{"issue":"3","key":"ppat.1014493.ref013","doi-asserted-by":"crossref","first-page":"611","DOI":"10.1046\/j.1365-2958.1998.00710.x","article-title":"The transferrin receptor expressed by gonococcal strain FA1090 is required for the experimental infection of human male volunteers","volume":"27","author":"CN Cornelissen","year":"1998","journal-title":"Mol Microbiol"},{"issue":"7","key":"ppat.1014493.ref014","doi-asserted-by":"crossref","first-page":"4281","DOI":"10.1128\/IAI.73.7.4281-4287.2005","article-title":"The gonococcal Fur-regulated tbpA and tbpB genes are expressed during natural mucosal gonococcal infection","volume":"73","author":"S Agarwal","year":"2005","journal-title":"Infect Immun"},{"issue":"4","key":"ppat.1014493.ref015","doi-asserted-by":"crossref","first-page":"175","DOI":"10.1006\/mpat.1998.0226","article-title":"Discrimination between apo and iron-loaded forms of transferrin by transferrin binding protein B and its N-terminal subfragment","volume":"25","author":"MD Retzer","year":"1998","journal-title":"Microb Pathog"},{"issue":"5","key":"ppat.1014493.ref016","doi-asserted-by":"crossref","first-page":"1960","DOI":"10.1128\/IAI.00020-08","article-title":"Identification of TbpA residues required for transferrin-iron utilization by Neisseria gonorrhoeae","volume":"76","author":"JM Noto","year":"2008","journal-title":"Infect Immun"},{"key":"ppat.1014493.ref017","doi-asserted-by":"crossref","first-page":"247","DOI":"10.3389\/fimmu.2019.00247","article-title":"Utility of Hybrid Transferrin Binding Protein Antigens for Protection Against Pathogenic Neisseria Species","volume":"10","author":"JE Fegan","year":"2019","journal-title":"Front Immunol"},{"key":"ppat.1014493.ref018","doi-asserted-by":"crossref","unstructured":"Marshall HS, McMillan M, Koehler AP, Lawrence A, Sullivan TR, MacLennan JM, et al. Meningococcal B Vaccine and Meningococcal Carriage in Adolescents in Australia. New England Journal of Medicine. 2020;382(4):318\u201327.","DOI":"10.1056\/NEJMoa1900236"},{"issue":"3","key":"ppat.1014493.ref019","doi-asserted-by":"crossref","DOI":"10.1093\/cid\/ciaa1733","article-title":"Effectiveness of Meningococcal Vaccines at Reducing Invasive Meningococcal Disease and Pharyngeal Neisseria meningitidis Carriage: A Systematic Review and Meta-analysis","volume":"73","author":"M McMillan","year":"2021","journal-title":"Clin Infect Dis"},{"issue":"10","key":"ppat.1014493.ref020","doi-asserted-by":"crossref","first-page":"1590","DOI":"10.1093\/infdis\/jix162","article-title":"Discordant Effects of Licensed Meningococcal Serogroup B Vaccination on Invasive Disease and Nasal Colonization in a Humanized Mouse Model","volume":"215","author":"CM Buckwalter","year":"2017","journal-title":"J Infect Dis"},{"issue":"9","key":"ppat.1014493.ref021","doi-asserted-by":"crossref","first-page":"4938","DOI":"10.1128\/IAI.68.9.4938-4947.2000","article-title":"Allelic diversity of the two transferrin binding protein B gene isotypes among a collection of Neisseria meningitidis strains representative of serogroup B disease: implication for the composition of a recombinant TbpB-based vaccine","volume":"68","author":"B Rokbi","year":"2000","journal-title":"Infect Immun"},{"issue":"1","key":"ppat.1014493.ref022","doi-asserted-by":"crossref","first-page":"10","DOI":"10.1038\/s41541-024-01054-0","article-title":"Rational selection of TbpB variants yields a bivalent vaccine with broad coverage against Neisseria gonorrhoeae","volume":"10","author":"JE Fegan","year":"2025","journal-title":"NPJ Vaccines"},{"issue":"5","key":"ppat.1014493.ref023","doi-asserted-by":"crossref","first-page":"1301","DOI":"10.1111\/j.1365-2958.2010.07289.x","article-title":"Delineating the regions of human transferrin involved in interactions with transferrin binding protein B from Neisseria meningitidis","volume":"77","author":"JML Ling","year":"2010","journal-title":"Mol Microbiol"},{"issue":"3","key":"ppat.1014493.ref024","doi-asserted-by":"crossref","first-page":"358","DOI":"10.1038\/nsmb.2251","article-title":"The structural basis of transferrin sequestration by transferrin-binding protein B","volume":"19","author":"C Calmettes","year":"2012","journal-title":"Nat Struct Mol Biol"},{"issue":"4","key":"ppat.1014493.ref025","doi-asserted-by":"crossref","first-page":"523","DOI":"10.1016\/j.molcel.2009.06.029","article-title":"Insights into the bacterial transferrin receptor: the structure of transferrin-binding protein B from Actinobacillus pleuropneumoniae","volume":"35","author":"TF Moraes","year":"2009","journal-title":"Mol Cell"},{"key":"ppat.1014493.ref026","doi-asserted-by":"crossref","first-page":"158","DOI":"10.3389\/fimmu.2020.00158","article-title":"Hybrid Antigens Expressing Surface Loops of ZnuD From Acinetobacter baumannii Is Capable of Inducing Protection Against Infection","volume":"11","author":"MM Qamsari","year":"2020","journal-title":"Front Immunol"},{"key":"ppat.1014493.ref027","doi-asserted-by":"crossref","first-page":"1222267","DOI":"10.3389\/fimmu.2023.1222267","article-title":"Use of Epivolve phage display to generate a monoclonal antibody with opsonic activity directed against a subdominant epitope on extracellular loop 4 of Treponema pallidum BamA (TP0326)","volume":"14","author":"MR Ferguson","year":"2023","journal-title":"Front Immunol"},{"issue":"8016","key":"ppat.1014493.ref028","doi-asserted-by":"crossref","first-page":"493","DOI":"10.1038\/s41586-024-07487-w","article-title":"Accurate structure prediction of biomolecular interactions with AlphaFold 3","volume":"630","author":"J Abramson","year":"2024","journal-title":"Nature"},{"issue":"3","key":"ppat.1014493.ref029","doi-asserted-by":"crossref","DOI":"10.1002\/pro.4582","article-title":"Using evolutionary data to make sense of macromolecules with a \u201cface-lifted\u201d ConSurf","volume":"32","author":"B Yariv","year":"2023","journal-title":"Protein Sci"},{"issue":"1","key":"ppat.1014493.ref030","doi-asserted-by":"crossref","first-page":"184","DOI":"10.1111\/febs.14696","article-title":"nanoDSF as screening tool for enzyme libraries and biotechnology development","volume":"286","author":"AO Magnusson","year":"2019","journal-title":"FEBS J"},{"issue":"1","key":"ppat.1014493.ref031","doi-asserted-by":"crossref","first-page":"10377","DOI":"10.1038\/s41598-017-10627-0","article-title":"New insights about functional and cross-reactive properties of antibodies generated against recombinant TbpBs of Haemophilus parasuis","volume":"7","author":"BM Barasuol","year":"2017","journal-title":"Sci Rep"},{"issue":"7","key":"ppat.1014493.ref032","doi-asserted-by":"crossref","DOI":"10.1371\/journal.ppat.1003509","article-title":"In vivo adaptation and persistence of Neisseria meningitidis within the nasopharyngeal mucosa","volume":"9","author":"KO Johswich","year":"2013","journal-title":"PLoS Pathog"},{"key":"ppat.1014493.ref033","doi-asserted-by":"crossref","first-page":"2222","DOI":"10.1016\/j.vaccine.2005.01.051","article-title":"Meningococcal surrogates of protection--serum bactericidal antibody activity","volume":"23","author":"R Borrow","year":"2005","journal-title":"Vaccine"},{"issue":"3","key":"ppat.1014493.ref034","doi-asserted-by":"crossref","first-page":"1030","DOI":"10.1128\/IAI.02572-14","article-title":"Nonbinding site-directed mutants of transferrin binding protein B exhibit enhanced immunogenicity and protective capabilities","volume":"83","author":"R Frandoloso","year":"2015","journal-title":"Infect Immun"},{"key":"ppat.1014493.ref035","doi-asserted-by":"crossref","first-page":"113037","DOI":"10.1016\/j.jim.2021.113037","article-title":"Development of a non-biased, high-throughput ELISA for the rapid evaluation of immunogenicity and cross-reactivity","volume":"493","author":"JE Fegan","year":"2021","journal-title":"J Immunol Methods"},{"issue":"9","key":"ppat.1014493.ref036","doi-asserted-by":"crossref","first-page":"811","DOI":"10.1038\/nsmb.3267","article-title":"Iterative structure-based improvement of a fusion-glycoprotein vaccine against RSV","volume":"23","author":"MG Joyce","year":"2016","journal-title":"Nat Struct Mol Biol"},{"issue":"9","key":"ppat.1014493.ref037","doi-asserted-by":"crossref","first-page":"2049","DOI":"10.1084\/jem.20052442","article-title":"Enhancing immunogenicity by limiting susceptibility to lysosomal proteolysis","volume":"203","author":"L Delamarre","year":"2006","journal-title":"J Exp Med"},{"issue":"6","key":"ppat.1014493.ref038","doi-asserted-by":"crossref","first-page":"1307","DOI":"10.1084\/jem.129.6.1307","article-title":"Human immunity to the meningococcus. I. The role of humoral antibodies","volume":"129","author":"I Goldschneider","year":"1969","journal-title":"J Exp Med"},{"issue":"3","key":"ppat.1014493.ref039","doi-asserted-by":"crossref","first-page":"295","DOI":"10.1007\/BF02918259","article-title":"Complement deficiency states and meningococcal disease","volume":"12","author":"J Figueroa","year":"1993","journal-title":"Immunol Res"},{"issue":"3","key":"ppat.1014493.ref040","doi-asserted-by":"crossref","first-page":"1561","DOI":"10.1128\/IAI.69.3.1561-1567.2001","article-title":"Recombinant Neisseria meningitidis transferrin binding protein A protects against experimental meningococcal infection","volume":"69","author":"D West","year":"2001","journal-title":"Infect Immun"},{"key":"ppat.1014493.ref041","doi-asserted-by":"crossref","first-page":"126709","DOI":"10.1016\/j.vaccine.2025.126709","article-title":"Adjuvant-dependent impacts on vaccine-induced humoral responses and protection in preclinical models of nasal and genital colonization by pathogenic Neisseria","volume":"48","author":"EA Islam","year":"2025","journal-title":"Vaccine"},{"issue":"1","key":"ppat.1014493.ref042","doi-asserted-by":"crossref","first-page":"103","DOI":"10.1080\/14760584.2022.2003708","article-title":"4CMenB vaccine and its role in preventing transmission and inducing herd immunity","volume":"21","author":"M McMillan","year":"2022","journal-title":"Expert Rev Vaccines"},{"key":"ppat.1014493.ref043","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1007\/978-1-62703-691-7_2","article-title":"Stable expression clones and auto-induction for protein production in E. coli","volume":"1091","author":"FW Studier","year":"2014","journal-title":"Methods Mol Biol"},{"key":"ppat.1014493.ref044","doi-asserted-by":"crossref","first-page":"307","DOI":"10.1016\/S0076-6879(97)76066-X","article-title":"Processing of X-ray diffraction data collected in oscillation mode","volume":"276","author":"Z Otwinowski","year":"1997","journal-title":"Methods Enzymol"},{"key":"ppat.1014493.ref045","doi-asserted-by":"crossref","first-page":"2276","DOI":"10.1107\/S0907444913022750","article-title":"Phaser.MRage: automated molecular replacement","volume":"69","author":"G Bunk\u00f3czi","year":"2013","journal-title":"Acta Crystallogr D Biol Crystallogr"},{"key":"ppat.1014493.ref046","doi-asserted-by":"crossref","first-page":"2126","DOI":"10.1107\/S0907444904019158","article-title":"Coot: model-building tools for molecular graphics","volume":"60","author":"P Emsley","year":"2004","journal-title":"Acta Crystallogr D Biol Crystallogr"},{"key":"ppat.1014493.ref047","doi-asserted-by":"crossref","first-page":"213","DOI":"10.1107\/S0907444909052925","article-title":"PHENIX: a comprehensive Python-based system for macromolecular structure solution","volume":"66","author":"PD Adams","year":"2010","journal-title":"Acta Crystallogr D Biol Crystallogr"},{"issue":"7","key":"ppat.1014493.ref048","doi-asserted-by":"crossref","first-page":"671","DOI":"10.1038\/nmeth.2089","article-title":"NIH Image to ImageJ: 25 years of image analysis","volume":"9","author":"CA Schneider","year":"2012","journal-title":"Nat Methods"},{"issue":"7","key":"ppat.1014493.ref049","doi-asserted-by":"crossref","first-page":"2346","DOI":"10.1128\/IAI.00293-12","article-title":"Invasive potential of nonencapsulated disease isolates of Neisseria meningitidis","volume":"80","author":"KO Johswich","year":"2012","journal-title":"Infect Immun"},{"issue":"9","key":"ppat.1014493.ref050","doi-asserted-by":"crossref","first-page":"1189","DOI":"10.1093\/bioinformatics\/btp033","article-title":"Jalview Version 2--a multiple sequence alignment editor and analysis workbench","volume":"25","author":"AM Waterhouse","year":"2009","journal-title":"Bioinformatics"}],"updated-by":[{"DOI":"10.1371\/journal.ppat.1014493","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2026,8,17]],"date-time":"2026-08-17T00:00:00Z","timestamp":1786924800000}}],"container-title":["PLOS Pathogens"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.ppat.1014493","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,17]],"date-time":"2026-08-17T17:41:00Z","timestamp":1786988460000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.ppat.1014493"}},"subtitle":[],"editor":[{"given":"Vladimir","family":"Pelicic","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2026,8,10]]},"references-count":50,"journal-issue":{"issue":"8","published-online":{"date-parts":[[2026,8,10]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.ppat.1014493","relation":{},"ISSN":["1553-7374"],"issn-type":[{"value":"1553-7374","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,8,10]]}}}