{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T05:16:18Z","timestamp":1790226978629,"version":"4.1.0"},"reference-count":20,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"6","license":[{"start":{"date-parts":[[2015,9,1]],"date-time":"2015-09-01T00:00:00Z","timestamp":1441065600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["lww.com","ovid.com"],"crossmark-restriction":true},"short-container-title":["Hepatology"],"published-print":{"date-parts":[[2016,12]]},"abstract":"<jats:p>\n                    Direct\u2010acting antivirals (DAAs) have led to a high cure rate in treated patients with chronic hepatitis C virus (HCV) infection, but this still leaves a large number of treatment failures secondary to the emergence of resistance\u2010associated variants (RAVs). To increase the barrier to resistance, a complementary strategy is to use neutralizing human monoclonal antibodies (HMAbs) to prevent acute infection. However, earlier efforts with the selected antibodies led to RAVs in animal and clinical studies. Therefore, we identified an HMAb that is less likely to elicit RAVs for affinity maturation to increase potency and, more important, breadth of protection. Selected matured antibodies show improved affinity and neutralization against a panel of diverse HCV isolates. Structural and modeling studies reveal that the affinity\u2010matured HMAb mediates virus neutralization, in part, by inducing conformational change to the targeted epitope, and that the maturated light chain is responsible for the improved affinity and breadth of protection. A matured HMAb protected humanized mice when challenged with an infectious HCV human serum inoculum for a prolonged period. However, a single mouse experienced breakthrough infection after 63 days when the serum HMAb concentration dropped by several logs; sequence analysis revealed no viral escape mutation.\n                    <jats:italic toggle=\"yes\">Conclusion<\/jats:italic>\n                    : The findings suggest that a single broadly neutralizing antibody can prevent acute HCV infection without inducing RAVs and may complement DAAs to reduce the emergence of RAVs. (H\n                    <jats:sc>epatology<\/jats:sc>\n                    2016;64:1922\u20101933).\n                  <\/jats:p>","DOI":"10.1002\/hep.28850","type":"journal-article","created":{"date-parts":[[2016,9,19]],"date-time":"2016-09-19T05:02:19Z","timestamp":1474261339000},"page":"1922-1933","update-policy":"https:\/\/doi.org\/10.1097\/lww.0000000000001000","source":"Crossref","is-referenced-by-count":80,"title":["Affinity maturation of a broadly neutralizing human monoclonal antibody that prevents acute hepatitis C virus infection in mice"],"prefix":"10.1097","volume":"64","author":[{"given":"Zhen\u2010Yong","family":"Keck","sequence":"first","affiliation":[{"name":"Department of Pathology,Stanford University School of Medicine,Stanford,CA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yong","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Pathology,Stanford University School of Medicine,Stanford,CA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patrick","family":"Lau","sequence":"additional","affiliation":[{"name":"Department of Pathology,Stanford University School of Medicine,Stanford,CA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Garry","family":"Lund","sequence":"additional","affiliation":[{"name":"KMT Hepatech, Inc,Edmonton,Alberta,Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sneha","family":"Rangarajan","sequence":"additional","affiliation":[{"name":"University of Maryland Institute for Bioscience and Biotechnology Research,Rockville,MD"},{"name":"Department of Cell Biology and Molecular Genetics,University of Maryland,College Park,MD"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Catherine","family":"Fauvelle","sequence":"additional","affiliation":[{"name":"Inserm, U1110,Institut de Recherche sur les Maladies Virales et H\u00e9patiques,Strasbourg,France"},{"name":"Universit\u00e9 de Strasbourg,Strasbourg,France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Grant C.","family":"Liao","sequence":"additional","affiliation":[{"name":"Integrated BioTherapeutics, Inc,Rockville,MD"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Frederick W.","family":"Holtsberg","sequence":"additional","affiliation":[{"name":"Integrated BioTherapeutics, Inc,Rockville,MD"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kelly L.","family":"Warfield","sequence":"additional","affiliation":[{"name":"Integrated BioTherapeutics, Inc,Rockville,MD"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M. 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