{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T04:17:44Z","timestamp":1787026664832,"version":"build-2736575974"},"reference-count":177,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,5,1]],"date-time":"2026-05-01T00:00:00Z","timestamp":1777593600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82304367"],"award-info":[{"award-number":["82304367"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:p>Respiratory syncytial virus (RSV) and severe acute respiratory syndrome coronavirus 2 (SARS\u2212CoV\u22122) represent two extremes in the outcome of antibody\u2212based interventions. The long\u2212acting monoclonal antibody nirsevimab has achieved durable, population\u2212level protection against RSV in infants, reducing hospitalizations by 70\u201390% with no evidence of antigenic escape. In contrast, all neutralizing monoclonal antibodies against SARS\u2212CoV\u22122 became obsolete within three years due to rapid viral evolution, particularly in the spike receptor\u2212binding domain. This review dissects the mechanistic determinants underlying this divergence. We propose four key principles that govern antibody efficacy against respiratory viruses: (i) targeting a structurally conserved epitope with high fitness cost for escape; (ii) achieving sufficient antibody concentrations in the airway epithelial lining fluid; (iii) the vulnerability of single\u2212epitope strategies against mutable viral targets; and (iv) the auxiliary but non\u2212substitutable role of Fc effector functions. By comparing RSV and SARS\u2212CoV\u22122, we illustrate how these principles align in successful interventions and fail in others. Finally, we discuss emerging strategies\u2014particularly inhaled delivery and mRNA\u2212encoded antibodies\u2014that may overcome current limitations and enable durable protection against antigenically variable respiratory pathogens.<\/jats:p>","DOI":"10.3389\/fimmu.2026.1818721","type":"journal-article","created":{"date-parts":[[2026,5,1]],"date-time":"2026-05-01T05:36:03Z","timestamp":1777613763000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":2,"title":["Determinants of success and failure of antibody-based strategies against respiratory viruses: insights from RSV and SARS-CoV-2"],"prefix":"10.3389","volume":"17","author":[{"given":"Hai","family":"Guo","sequence":"first","affiliation":[{"name":"Department of Thoracic Surgery, West China Hospital, Sichuan University","place":["Chengdu, Sichuan, 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