{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,3]],"date-time":"2026-09-03T04:20:03Z","timestamp":1788409203650,"version":"build-2803163510"},"reference-count":33,"publisher":"American Society for Microbiology","issue":"8","license":[{"start":{"date-parts":[[2016,8,1]],"date-time":"2016-08-01T00:00:00Z","timestamp":1470009600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"funder":[{"DOI":"10.13039\/100004336","name":"Novartis","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100004336","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["Antimicrob Agents Chemother"],"published-print":{"date-parts":[[2016,8]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n          <jats:p>\n            Human cytomegalovirus (HCMV) infection is usually benign in healthy individuals but can cause life-threatening disease in those with compromised immune systems. Approved drugs available to treat HCMV disease, including ganciclovir, cidofovir, and foscarnet, have significant toxicities that limit their use in certain patient populations. LJP538 and LJP539 are human monoclonal antibodies that are being evaluated as immunoglobulin therapeutics. The antibodies target glycoproteins gB and the gH\/gL\/UL128\/UL130\/UL131a pentameric complex, respectively. Here we present an\n            <jats:italic>in vitro<\/jats:italic>\n            characterization of these antibodies. We show that LJP538 and LJP539 are more potent than a marketed immunoglobulin at inhibiting HCMV infection of various cell lines relevant to pathogenesis. We find that LJP538 and LJP539 are active against a panel of clinical isolates\n            <jats:italic>in vitro<\/jats:italic>\n            and demonstrate minor-to-moderate synergy in combination. Passage of HCMV in the presence of LJP538 or LJP539 alone resulted in resistance-associated mutations that mapped to the target genes. However, no loss of susceptibility to the combination of antibodies was observed for &gt;400 days in culture. Finally, the binding regions of LJP538 and LJP539 are conserved among clinical isolates. Taken together, these data support the use of LJP538 and LJP539 in combination for clinical trials in HCMV patients.\n          <\/jats:p>","DOI":"10.1128\/aac.00382-16","type":"journal-article","created":{"date-parts":[[2016,6,7]],"date-time":"2016-06-07T03:23:45Z","timestamp":1465269825000},"page":"4961-4971","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":31,"title":["<i>In Vitro<\/i>\n            Characterization of Human Cytomegalovirus-Targeting Therapeutic Monoclonal Antibodies LJP538 and LJP539"],"prefix":"10.1128","volume":"60","author":[{"given":"Hetalkumar D.","family":"Patel","sequence":"first","affiliation":[{"name":"Novartis Institutes for BioMedical Research, Infectious Disease Area, Emeryville, California, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pavel","family":"Nikitin","sequence":"additional","affiliation":[{"name":"Novartis Institutes for BioMedical Research, Infectious Disease Area, Emeryville, California, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas","family":"Gesner","sequence":"additional","affiliation":[{"name":"Novartis Institutes for BioMedical Research, Infectious Disease Area, Emeryville, California, USA"},{"name":"Novartis Vaccines, Cambridge, Massachusetts, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James J.","family":"Lin","sequence":"additional","affiliation":[{"name":"Novartis Institutes for BioMedical Research, Infectious Disease Area, Emeryville, California, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David T.","family":"Barkan","sequence":"additional","affiliation":[{"name":"Novartis Institutes for BioMedical Research, Infectious Disease Area, Emeryville, California, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Claudio","family":"Ciferri","sequence":"additional","affiliation":[{"name":"Novartis Vaccines, Cambridge, Massachusetts, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrea","family":"Carfi","sequence":"additional","affiliation":[{"name":"Novartis Vaccines, Cambridge, Massachusetts, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tahmineh","family":"Akbarnejad Yazdi","sequence":"additional","affiliation":[{"name":"Novartis Institutes for BioMedical Research, Infectious Disease Area, Emeryville, California, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter","family":"Skewes-Cox","sequence":"additional","affiliation":[{"name":"Novartis Institutes for BioMedical Research, Infectious Disease Area, Emeryville, California, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brigitte","family":"Wiedmann","sequence":"additional","affiliation":[{"name":"Novartis Institutes for BioMedical Research, Infectious Disease Area, Emeryville, California, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nadine","family":"Jarousse","sequence":"additional","affiliation":[{"name":"Novartis Institutes for BioMedical Research, Infectious Disease Area, Emeryville, California, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Weidong","family":"Zhong","sequence":"additional","affiliation":[{"name":"Novartis Institutes for BioMedical Research, Infectious Disease Area, Emeryville, California, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adam","family":"Feire","sequence":"additional","affiliation":[{"name":"Novartis Institutes for BioMedical Research, Infectious Disease Area, Emeryville, California, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christy M.","family":"Hebner","sequence":"additional","affiliation":[{"name":"Novartis Institutes for BioMedical Research, Infectious Disease Area, Emeryville, California, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1086\/590934"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2008-10-143560"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa043337"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1128\/CVI.00509-12"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1310214"},{"key":"e_1_3_3_7_2","first-page":"63","article-title":"Cytomegalovirus cell tropism","volume":"325","author":"Sinzger C","year":"2008","unstructured":"Sinzger C, Digel M, Jahn G. 2008. Cytomegalovirus cell tropism. Curr Top Microbiol Immunol 325:63\u201383.","journal-title":"Curr Top Microbiol Immunol"},{"key":"e_1_3_3_8_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.78.18.10023-10033.2004"},{"key":"e_1_3_3_9_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0509201102"},{"key":"e_1_3_3_10_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.01325-15"},{"key":"e_1_3_3_11_2","doi-asserted-by":"publisher","DOI":"10.1093\/infdis\/165.2.381"},{"key":"e_1_3_3_12_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.vaccine.2011.09.056"},{"key":"e_1_3_3_13_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.00467-12"},{"key":"e_1_3_3_14_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.01809-09"},{"key":"e_1_3_3_15_2","first-page":"1311","article-title":"Biological efficacy of a chimeric antibody to the epidermal growth factor receptor in a human tumor xenograft model","volume":"1","author":"Goldstein NI","year":"1995","unstructured":"Goldstein NI, Prewett M, Zuklys K, Rockwell P, Mendelsohn J. 1995. Biological efficacy of a chimeric antibody to the epidermal growth factor receptor in a human tumor xenograft model. Clin Cancer Res 1:1311\u20131318.","journal-title":"Clin Cancer Res"},{"key":"e_1_3_3_16_2","doi-asserted-by":"publisher","DOI":"10.1016\/0166-3542(94)90048-5"},{"key":"e_1_3_3_17_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.chom.2011.07.010"},{"key":"e_1_3_3_18_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.antiviral.2011.01.007"},{"key":"e_1_3_3_19_2","doi-asserted-by":"publisher","DOI":"10.1093\/infdis\/163.6.1229"},{"key":"e_1_3_3_20_2","doi-asserted-by":"publisher","DOI":"10.1093\/infdis\/166.3.604"},{"key":"e_1_3_3_21_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1083-8791(01)80005-7"},{"key":"e_1_3_3_22_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1004377"},{"key":"e_1_3_3_23_2","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms9176"},{"key":"e_1_3_3_24_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1001256"},{"key":"e_1_3_3_25_2","doi-asserted-by":"publisher","DOI":"10.1099\/vir.0.83523-0"},{"key":"e_1_3_3_26_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.01623-08"},{"key":"e_1_3_3_27_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.virol.2013.06.002"},{"key":"e_1_3_3_28_2","doi-asserted-by":"publisher","DOI":"10.1016\/B978-0-12-800147-9.00005-4"},{"key":"e_1_3_3_29_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.76.17.8596-8608.2002"},{"key":"e_1_3_3_30_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.vaccine.2008.07.092"},{"key":"e_1_3_3_31_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1004060"},{"key":"e_1_3_3_32_2","doi-asserted-by":"publisher","DOI":"10.2217\/fvl.13.107"},{"key":"e_1_3_3_33_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa0804749"},{"key":"e_1_3_3_34_2","volume-title":"MacSynergy II manual","author":"Prichard MN","year":"1993","unstructured":"Prichard MN, Aseltine KR, Shipman CJ. 1993. MacSynergy II manual. University of Alabama at Birmingham, Birmingham, Alabama. http:\/\/www.uab.edu\/images\/pediatrics\/ID\/MacSynergy.pdf."}],"container-title":["Antimicrobial Agents and Chemotherapy"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/AAC.00382-16","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/AAC.00382-16","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,2,21]],"date-time":"2022-02-21T20:55:37Z","timestamp":1645476937000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.asm.org\/doi\/10.1128\/AAC.00382-16"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2016,8]]},"references-count":33,"journal-issue":{"issue":"8","published-print":{"date-parts":[[2016,8]]}},"alternative-id":["10.1128\/AAC.00382-16"],"URL":"https:\/\/doi.org\/10.1128\/aac.00382-16","relation":{},"ISSN":["0066-4804","1098-6596"],"issn-type":[{"value":"0066-4804","type":"print"},{"value":"1098-6596","type":"electronic"}],"subject":[],"published":{"date-parts":[[2016,8]]},"assertion":[{"value":"2016-02-17","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2016-06-03","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2016-07-22","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}