{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,27]],"date-time":"2026-08-27T13:47:00Z","timestamp":1787838420930,"version":"build-2784847793"},"update-to":[{"DOI":"10.1371\/journal.ppat.1012623","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2024,10,25]],"date-time":"2024-10-25T00:00:00Z","timestamp":1729814400000}}],"reference-count":67,"publisher":"Public Library of Science (PLoS)","issue":"10","license":[{"start":{"date-parts":[[2024,10,15]],"date-time":"2024-10-15T00:00:00Z","timestamp":1728950400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100012166","name":"National Key R&D Program of China","doi-asserted-by":"crossref","award":["2021YFD1800304"],"award-info":[{"award-number":["2021YFD1800304"]}],"id":[{"id":"10.13039\/501100012166","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["32373028"],"award-info":[{"award-number":["32373028"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["32171300"],"award-info":[{"award-number":["32171300"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["32072873"],"award-info":[{"award-number":["32072873"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["32302884"],"award-info":[{"award-number":["32302884"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100012226","name":"Fundamental Research Funds for the Central Universities","doi-asserted-by":"publisher","award":["lzujbky-2021-ct05"],"award-info":[{"award-number":["lzujbky-2021-ct05"]}],"id":[{"id":"10.13039\/501100012226","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.plospathogens.org"],"crossmark-restriction":false},"short-container-title":["PLoS Pathog"],"abstract":"<jats:p>It is a great challenge to isolate the broadly neutralizing antibodies (bnAbs) against foot-and-mouth disease virus (FMDV) due to its existence as seven distinct serotypes without cross-protection. Here, by vaccination of pig with FMDV serotypes O and A whole virus antigens, we obtained 10 bnAbs against serotypes O, A and\/or Asia1 by dissecting 216 common clonotypes of two serotypes O and A specific porcine B-cell receptor (BCR) gene repertoires containing total 12720 B cell clones, indicating the induction of cross-serotype bnAbs after sequential vaccination with serotypes O and A antigens. The majority of porcine bnAbs (9\/10) were derived from terminally differentiated B cells of different clonal lineages, which convergently targeted the conserved \u201cRGDL\u201d motif on structural protein VP1 of FMDV by mimicking receptor recognition to inhibit viral attachment to cells. Cryo-EM complex structures revealed that the other bnAb pOA-2 specifically targets a novel inter-pentamer antigen structure surrounding the viral three-fold axis, with a highly conserved determinant at residue 68 on VP2. This unique binding pattern enabled cross-serotype neutralization by destabilizing the viral particle. The evolutionary analysis of pOA-2 demonstrated its origin from an intermediate B-cell, emphasizing the crucial role of somatic hypermutations (SHMs) in balancing the breadth and potency of neutralization. However, excessive SHMs may deviate from the trajectory of broad neutralization. This study provides a strategy to uncover bnAbs against highly mutable pathogens and the cross-serotype antigenic structures to explore broadly protective FMDV vaccine.<\/jats:p>","DOI":"10.1371\/journal.ppat.1012623","type":"journal-article","created":{"date-parts":[[2024,10,15]],"date-time":"2024-10-15T17:34:47Z","timestamp":1729013687000},"page":"e1012623","update-policy":"https:\/\/doi.org\/10.1371\/journal.ppat.corrections_policy","source":"Crossref","is-referenced-by-count":14,"title":["Discovery, recognized antigenic structures, and evolution of cross-serotype broadly neutralizing antibodies from porcine B-cell repertoires against foot-and-mouth disease virus"],"prefix":"10.1371","volume":"20","author":[{"given":"Fengjuan","family":"Li","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shanquan","family":"Wu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lv","family":"Lv","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shulun","family":"Huang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zelin","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhaxi","family":"Zerang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pinghua","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yimei","family":"Cao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huifang","family":"Bao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pu","family":"Sun","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xingwen","family":"Bai","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yong","family":"He","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuanfang","family":"Fu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hong","family":"Yuan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xueqing","family":"Ma","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhixun","family":"Zhao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jing","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jian","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tao","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dong","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qiang","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jijun","family":"He","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zaixin","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zengjun","family":"Lu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dongsheng","family":"Lei","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8307-634X","authenticated-orcid":true,"given":"Kun","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2024,10,15]]},"reference":[{"issue":"9","key":"ppat.1012623.ref001","doi-asserted-by":"crossref","first-page":"1409","DOI":"10.3201\/eid1509.090091","article-title":"Genetic 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Pybus, A Phylogenetic Codon Substitution Model for Antibody Lineages","volume":"206","author":"KB Hoehn","year":"2017","journal-title":"Genetics"},{"issue":"Pt 8","key":"ppat.1012623.ref032","doi-asserted-by":"crossref","first-page":"2001","DOI":"10.1099\/0022-1317-83-8-2001","article-title":"A divalent antibody format is required for neutralization of human cytomegalovirus via antigenic domain 2 on glycoprotein B","volume":"83","author":"J Lantto","year":"2002","journal-title":"J Gen Virol"},{"issue":"11","key":"ppat.1012623.ref033","doi-asserted-by":"crossref","first-page":"e00071","DOI":"10.1128\/jvi.00071-22","article-title":"Somatic Hypermutation and Framework Mutations of Variable Region Contribute to Anti-Zika Virus-Specific Monoclonal Antibody Binding and Function","volume":"96","author":"I Tsuji","year":"2022","journal-title":"Journal of Virology"},{"issue":"4","key":"ppat.1012623.ref034","doi-asserted-by":"crossref","first-page":"770","DOI":"10.1073\/pnas.1616502114","article-title":"Potent neutralization of hepatitis A virus reveals a receptor mimic mechanism and the receptor recognition site","volume":"114","author":"X Wang","year":"2017","journal-title":"Proc Natl Acad Sci U S A"},{"issue":"30","key":"ppat.1012623.ref035","doi-asserted-by":"crossref","first-page":"8017","DOI":"10.1073\/pnas.1707369114","article-title":"Antibody-induced uncoating of human rhinovirus B14","volume":"114","author":"Y Dong","year":"2017","journal-title":"Proc Natl Acad Sci U S A"},{"issue":"4","key":"ppat.1012623.ref036","article-title":"Neutralization Mechanisms of Two Highly Potent Antibodies against Human Enterovirus 71","volume":"9","author":"L Zhu","year":"2018","journal-title":"mBio"},{"issue":"1","key":"ppat.1012623.ref037","doi-asserted-by":"crossref","first-page":"56","DOI":"10.3390\/ph16010056","article-title":"RGD Forever!-Past, Present, and Future of a 3-Letter-Code in Radiopharmacy and Life Sciences","volume":"16","author":"J. 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