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A significant reduction in HCV viremia was observed in one of three treated animals without apparent hepatocellular injury. Viremia rebounded in the responder animal when antibody treatment was discontinued. Control of HCV replication was associated with restoration of intrahepatic CD4+ and CD8+ T-cell immunity against multiple HCV proteins. The responder animal had a history of broader T-cell immunity to multiple HCV proteins than the two chimpanzees that did not respond to PD-1 therapy. The results suggest that successful PD-1 blockade likely requires a critical threshold of preexisting virus-specific T cells in liver and warrants consideration of therapeutic vaccination strategies in combination with PD-1 blockade to broaden narrow responses. Anti\u2013PD-1 immunotherapy may also facilitate control of other persistent viruses, notably the hepatitis B virus where options for long-term control of virus replication are limited.<\/jats:p>","DOI":"10.1073\/pnas.1312772110","type":"journal-article","created":{"date-parts":[[2013,8,26]],"date-time":"2013-08-26T22:24:39Z","timestamp":1377555879000},"page":"15001-15006","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":157,"title":["Immunotherapy of chronic hepatitis C virus infection with antibodies against programmed cell death-1 (PD-1)"],"prefix":"10.1073","volume":"110","author":[{"given":"Michael J.","family":"Fuller","sequence":"first","affiliation":[{"name":"Center for Vaccines and Immunity, Nationwide Children\u2019s Hospital, Columbus, OH 43205;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Benoit","family":"Callendret","sequence":"additional","affiliation":[{"name":"Center for Vaccines and Immunity, Nationwide Children\u2019s Hospital, Columbus, OH 43205;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Baogong","family":"Zhu","sequence":"additional","affiliation":[{"name":"Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA 02115;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gordon J.","family":"Freeman","sequence":"additional","affiliation":[{"name":"Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA 02115;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dana L.","family":"Hasselschwert","sequence":"additional","affiliation":[{"name":"New Iberia Research Center, University of Louisiana at Lafayette, New Iberia, LA 70560;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"William","family":"Satterfield","sequence":"additional","affiliation":[{"name":"Department of Veterinary Sciences, Michale E. 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