{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,4,11]],"date-time":"2026-04-11T20:43:40Z","timestamp":1775940220657,"version":"3.50.1"},"posted":{"date-parts":[[2025,3,11]]},"group-title":"Immunology","reference-count":54,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2025,3,11]],"date-time":"2025-03-11T00:00:00Z","timestamp":1741651200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2025,3,10]]},"abstract":"<jats:title>SUMMARY<\/jats:title>\n                <jats:p>\n                  Public antibodies that recognize conserved epitopes are critical for vaccine development, and identifying somatic hypermutations (SHMs) that enhance antigen affinity in these public responses is key to guiding vaccine design for better protection. We propose that affinity-enhancing SHMs are selectively enriched in public antibody clonotypes, surpassing the background frequency seen in antibodies carrying the same V genes, but with different epitope specificities. Employing a human\n                  <jats:italic>IGHV4-59<\/jats:italic>\n                  \/\n                  <jats:italic>IGKV3-20<\/jats:italic>\n                  public antibody as a model, we compare SHM signatures in antibodies also using these V genes, but recognizing other epitopes. Critically, this comparison identified clonotype-enriched mutations in the light chain. Our analyses also show that these SHMs, in combination, enhance binding to a previously uncharacterized viral epitope, with antibody responses to it increasing after multiple vaccinations. Our findings offer a framework for identifying affinity-enhancing SHMs in public antibodies based on convergence and clonotype-enrichment and can help guide vaccine design aimed to elicit public antibodies.\n                <\/jats:p>\n                <jats:sec>\n                  <jats:title>Graphical Abstract<\/jats:title>\n                  <jats:fig id=\"ufig1\" position=\"float\" orientation=\"portrait\" fig-type=\"figure\">\n                    <jats:graphic xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"642041v1_ufig1\" position=\"float\" orientation=\"portrait\"\/>\n                  <\/jats:fig>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Highlights<\/jats:title>\n                  <jats:list list-type=\"bullet\">\n                    <jats:list-item>\n                      <jats:p>Clonotype-enriched SHMs are identified in the light chain of a public antibody, M15<\/jats:p>\n                    <\/jats:list-item>\n                    <jats:list-item>\n                      <jats:p>These light chain SHMs enhance affinity of M15<\/jats:p>\n                    <\/jats:list-item>\n                    <jats:list-item>\n                      <jats:p>M15 targets a previously undescribed, conserved viral epitope<\/jats:p>\n                    <\/jats:list-item>\n                    <jats:list-item>\n                      <jats:p>Serum antibody levels targeting this epitope increase after repeated vaccinations<\/jats:p>\n                    <\/jats:list-item>\n                  <\/jats:list>\n                <\/jats:sec>","DOI":"10.1101\/2025.03.07.642041","type":"posted-content","created":{"date-parts":[[2025,3,11]],"date-time":"2025-03-11T06:11:10Z","timestamp":1741673470000},"source":"Crossref","is-referenced-by-count":2,"title":["Convergent and clonotype-enriched mutations in the light chain drive affinity maturation of a public antibody"],"prefix":"10.64898","author":[{"given":"Vishal","family":"Rao","sequence":"first","affiliation":[{"name":"Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY, USA"},{"name":"Center for Vaccine Research and Pandemic Preparedness, Icahn School of Medicine at Mount Sinai, New York, NY, USA"},{"name":"Graduate School of Biomedical Sciences, Icahn School of Medicine at Mount Sinai, New York, NY, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Iden","family":"Sapse","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY, USA"},{"name":"Graduate School of Biomedical Sciences, Icahn School of Medicine at Mount Sinai, New York, NY, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hallie","family":"Cohn","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY, 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