{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,15]],"date-time":"2026-06-15T05:55:18Z","timestamp":1781502918952,"version":"3.54.1"},"reference-count":24,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,6,15]],"date-time":"2026-06-15T00:00:00Z","timestamp":1781481600000},"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>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Sarbecoviruses pose a persistent pandemic threat due to their zoonotic potential and high recombination capacity. This study investigated how disease severity influences cross-reactive antibody responses and the isolation of cross-neutralizing monoclonal antibodies.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Plasma samples from 67 COVID-19 convalescents (severe, n=17; non-severe, n=50) were compared for cross-reactive antibody responses against seven sarbecovirus spike proteins. Memory B cells were sorted using dual S1\/S2 fluorescent probes to isolate monoclonal antibodies.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Severe convalescents exhibited significantly higher neutralization titers against six animal-derived sarbecoviruses, responses that persisted for up to one year and were further enhanced by vaccination. From dual-targeting B cells, we isolated mAb 1D6, which simultaneously engages the S1 (ACE2-blocking) and S2 (fusion-inhibiting) domains. mAb 1D6 neutralized SARS-CoV-2 (IC50\u00a0=\u00a05.708 \u03bcg\/mL) and pangolin-CoV-GD (IC50\u00a0=\u00a014.02 \u03bcg\/mL). In contrast, antibody 1F2 bound both S1 and S2 across all tested sarbecoviruses but lacked neutralizing activity.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Severe COVID-19 was associated with broader and more durable cross-sarbecovirus antibody responses. The dual-targeting antibody 1D6 provides proof-of-concept for a cross-neutralization strategy, although its modest potency requires further optimization for therapeutic application.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fimmu.2026.1839618","type":"journal-article","created":{"date-parts":[[2026,6,15]],"date-time":"2026-06-15T05:36:48Z","timestamp":1781501808000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Severity-associated cross-reactive anti-sarbecovirus antibody responses in COVID-19 convalescents and isolation of a dual-targeting monoclonal antibody with cross-neutralizing activity"],"prefix":"10.3389","volume":"17","author":[{"given":"Qian","family":"Wu","sequence":"first","affiliation":[{"name":"Translational Medicine Institute & Neurological Medicine Institute, The First People\u2019s Hospital of Chenzhou, The First Clinical College, Xiangnan University","place":["Chenzhou, China"]},{"name":"Department of Laboratory Medicine, the Third Affiliated Hospital of Sun Yat-sen University","place":["Guangzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ling","family":"Niu","sequence":"additional","affiliation":[{"name":"Translational Medicine Institute & Neurological Medicine Institute, The First People\u2019s Hospital of Chenzhou, The First Clinical College, Xiangnan University","place":["Chenzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yueyang","family":"Zhang","sequence":"additional","affiliation":[{"name":"Translational Medicine Institute & Neurological Medicine Institute, The First People\u2019s Hospital of Chenzhou, The First Clinical College, Xiangnan University","place":["Chenzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tan","family":"Tan","sequence":"additional","affiliation":[{"name":"Translational Medicine Institute & Neurological Medicine Institute, The First People\u2019s Hospital of Chenzhou, The First Clinical College, Xiangnan University","place":["Chenzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuchen","family":"Yang","sequence":"additional","affiliation":[{"name":"Biology Teaching & Research Group, Linyi Middle School of Chenzhou","place":["Chenzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuang","family":"Li","sequence":"additional","affiliation":[{"name":"Translational Medicine Institute & Neurological Medicine Institute, The First People\u2019s Hospital of Chenzhou, The First Clinical College, Xiangnan University","place":["Chenzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bo","family":"Liu","sequence":"additional","affiliation":[{"name":"Translational Medicine Institute & Neurological Medicine Institute, The First People\u2019s Hospital of Chenzhou, The First Clinical College, Xiangnan University","place":["Chenzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jun","family":"Chen","sequence":"additional","affiliation":[{"name":"Translational Medicine Institute & Neurological Medicine Institute, The First People\u2019s Hospital of Chenzhou, The First Clinical College, Xiangnan University","place":["Chenzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chun","family":"Huang","sequence":"additional","affiliation":[{"name":"Translational Medicine Institute & Neurological Medicine Institute, The First People\u2019s Hospital of Chenzhou, The First Clinical College, Xiangnan University","place":["Chenzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qijie","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Infectious Disease, The Central Hospital of Shaoyang","place":["Shaoyang, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yabin","family":"Hu","sequence":"additional","affiliation":[{"name":"Translational Medicine Institute & Neurological Medicine Institute, The First People\u2019s Hospital of Chenzhou, The First Clinical College, Xiangnan University","place":["Chenzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,6,15]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1038\/s41579-018-0118-9","article-title":"Origin and evolution of pathogenic coronaviruses","volume":"17","author":"Cui","year":"2019","journal-title":"Nat Rev Microbiol"},{"key":"B2","doi-asserted-by":"publisher","first-page":"4380","DOI":"10.1016\/j.cell.2021.06.008","article-title":"Identification of novel bat coronaviruses sheds light on the evolutionary origins of SARS-CoV-2 and related 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