{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T05:16:50Z","timestamp":1790227010634,"version":"4.1.0"},"reference-count":57,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"4","license":[{"start":{"date-parts":[[2016,2,22]],"date-time":"2016-02-22T00:00:00Z","timestamp":1456099200000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1"},{"start":{"date-parts":[[2016,2,22]],"date-time":"2016-02-22T00:00:00Z","timestamp":1456099200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions"}],"content-domain":{"domain":["lww.com","ovid.com"],"crossmark-restriction":true},"short-container-title":["Hepatology"],"published-print":{"date-parts":[[2016,4]]},"abstract":"<jats:p>End\u2010stage liver disease (ESLD) caused by hepatitis C virus (HCV) infection is a major indication for liver transplantation. However, immediately after transplantation, the liver graft of viremic patients universally becomes infected by circulating virus, resulting in accelerated liver disease progression. Currently available direct\u2010acting antiviral therapies have reduced efficacy in patients with ESLD and prophylactic strategies to prevent HCV recurrence are still highly needed. In this study, we compared the ability of two broadly reactive monoclonal antibodies (mAbs), designated 3\/11 and AP33, recognizing a distinct, but overlapping, epitope in the viral E2 glycoprotein to protect humanized mice from a patient\u2010derived HCV challenge. Their neutralizing activity was assessed using the HCV pseudoparticles and cell\u2010culture\u2013derived HCV systems expressing multiple patient\u2010derived envelopes and a human\u2010liver chimeric mouse model. HCV RNA was readily detected in all control mice challenged with a patient\u2010derived HCV genotype 1b isolate, whereas 3 of 4 AP33\u2010treated mice were completely protected. In contrast, only one of four 3\/11\u2010treated mice remained HCV\u2010RNA negative throughout the observation period, whereas the other 3 had a viral load that was indistinguishable from that in the control group. The increased <jats:italic toggle=\"yes\">in vivo<\/jats:italic> efficacy of AP33 was in line with its higher affinity and neutralizing capacity observed <jats:italic toggle=\"yes\">in vitro<\/jats:italic>. <jats:italic toggle=\"yes\">Conclusions:<\/jats:italic> Although mAbs AP33 and 3\/11 target the same region in E2, only mAb AP33 can efficiently protect from challenge with a heterologous HCV population <jats:italic toggle=\"yes\">in vivo<\/jats:italic>. Given that mAb AP33 efficiently neutralizes viral variants that escaped the humoral immune response and reinfected the liver graft of transplant patients, it may be a valuable candidate to prevent HCV recurrence. In addition, our data are valuable for the design of a prophylactic vaccine. 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