{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,1]],"date-time":"2026-06-01T12:58:59Z","timestamp":1780318739650,"version":"3.54.1"},"update-to":[{"DOI":"10.1371\/journal.ppat.1013674","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2025,11,21]],"date-time":"2025-11-21T00:00:00Z","timestamp":1763683200000}}],"reference-count":48,"publisher":"Public Library of Science (PLoS)","issue":"11","license":[{"start":{"date-parts":[[2025,11,17]],"date-time":"2025-11-17T00:00:00Z","timestamp":1763337600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["32271256"],"award-info":[{"award-number":["32271256"]}],"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":["32300146"],"award-info":[{"award-number":["32300146"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Major Project of Guangzhou National Laboratory","award":["GZNL2023A01002"],"award-info":[{"award-number":["GZNL2023A01002"]}]},{"name":"Tianjin Science and Technology Major Project","award":["24ZXZSSS00490"],"award-info":[{"award-number":["24ZXZSSS00490"]}]}],"content-domain":{"domain":["www.plospathogens.org"],"crossmark-restriction":false},"short-container-title":["PLoS Pathog"],"abstract":"<jats:p>\n                    Respiratory syncytial virus (RSV) is a leading cause of lower respiratory tract infections among infants and older adults, posing a significant threat to global public health. The prophylactic use of neutralizing antibodies (nAbs) underscores the need to understand elite RSV antibody neutralization mechanisms, which is fundamental for developing next-generation therapies with enhanced potency and broader activity. In this study, we utilized H2L2 transgenic mice encoding human immunoglobulin variable regions for immunization and successfully screened multiple antibodies with significant neutralizing activity using the Beacon Optofluidic system. One of these antibodies, PR306007, exhibited significantly superior broad-spectrum neutralization against both RSV-A and B subgroups. Cryo-electron microscopy (Cryo-EM) structural analysis revealed that PR306007 binds to a unique epitope that overlaps with antigenic sites II and V of the F protein, with its primary binding regions located at the base of the \u03b16 and \u03b17 helices of site II, and residues S173 and N175 of site V. This binding mode offers valuable insights into enhanced neutralization activity and potentially reduces the risk of emerging immune evasive mutants. Furthermore, PR306007 showed potent\n                    <jats:italic>in vivo<\/jats:italic>\n                    antiviral activity against RSV infection and demonstrated good efficacy against both lower and upper respiratory tract infections, making it a promising prophylactic candidate for broad prevention. These findings provide new insights for the future development of RSV vaccines or nAbs.\n                  <\/jats:p>","DOI":"10.1371\/journal.ppat.1013674","type":"journal-article","created":{"date-parts":[[2025,11,17]],"date-time":"2025-11-17T18:43:00Z","timestamp":1763404980000},"page":"e1013674","update-policy":"https:\/\/doi.org\/10.1371\/journal.ppat.corrections_policy","source":"Crossref","is-referenced-by-count":2,"title":["Discovery and molecular mechanism of potent neutralizing antibody from humanized mice with respiratory syncytial 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Factors for Poor Outcome or Death in Young Children With Respiratory Syncytial Virus-Associated Acute Lower Respiratory Tract Infection: A Systematic Review and Meta-Analysis","volume":"226","author":"T Shi","year":"2022","journal-title":"J Infect Dis"},{"issue":"9725","key":"ppat.1013674.ref002","doi-asserted-by":"crossref","first-page":"1545","DOI":"10.1016\/S0140-6736(10)60206-1","article-title":"Global burden of acute lower respiratory infections due to respiratory syncytial virus in young children: a systematic review and meta-analysis","volume":"375","author":"H Nair","year":"2010","journal-title":"Lancet"},{"issue":"7","key":"ppat.1013674.ref003","doi-asserted-by":"crossref","first-page":"499","DOI":"10.1016\/S2213-2600(24)00184-X","article-title":"Respiratory syncytial virus vaccines: the future is bright","volume":"12","author":"The Lancet Respiratory Medicine","year":"2024","journal-title":"Lancet Respir 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