{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T20:53:46Z","timestamp":1790110426168,"version":"4.0.1"},"reference-count":46,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2023,5,15]],"date-time":"2023-05-15T00:00:00Z","timestamp":1684108800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100013996","name":"Global Health Innovative Technology Fund","doi-asserted-by":"publisher","award":["G2016-217"],"award-info":[{"award-number":["G2016-217"]}],"id":[{"id":"10.13039\/501100013996","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Antibodies"],"abstract":"<jats:p>To combat infectious diseases, vaccines are considered the best prophylactic strategy for a wide range of the population, but even when vaccines are effective, the administration of therapeutic antibodies against viruses could provide further treatment options, particularly for vulnerable groups whose immunity against the viruses is compromised. Therapeutic antibodies against dengue are ideally engineered to abrogate binding to Fc\u03b3 receptors (Fc\u03b3Rs), which can induce antibody-dependent enhancement (ADE). However, the Fc effector functions of neutralizing antibodies against SARS-CoV-2 have recently been reported to improve post-exposure therapy, while they are dispensable when administered as prophylaxis. Hence, in this report, we investigated the influence of Fc engineering on anti-virus efficacy using the anti-dengue\/Zika human antibody SIgN-3C and found it affected the viremia clearance efficacy against dengue in a mouse model. Furthermore, we demonstrated that complement activation through antibody binding to C1q could play a role in anti-dengue efficacy. We also generated a novel Fc variant, which displayed the ability for complement activation but showed very low Fc\u03b3R binding and an undetectable level of the risk of ADE in a cell-based assay. This Fc engineering approach could make effective and safe anti-virus antibodies against dengue, Zika and other viruses.<\/jats:p>","DOI":"10.3390\/antib12020036","type":"journal-article","created":{"date-parts":[[2023,5,16]],"date-time":"2023-05-16T02:27:04Z","timestamp":1684204024000},"page":"36","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Complement Activation by an Anti-Dengue\/Zika Antibody with Impaired Fc\u03b3 Receptor Binding Provides Strong Efficacy and Abrogates Risk of Antibody-Dependent Enhancement"],"prefix":"10.3390","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5343-4468","authenticated-orcid":false,"given":"Zenjiro","family":"Sampei","sequence":"first","affiliation":[{"name":"Chugai Pharmaceutical Co., Ltd., Yokohama 244-8602, Japan"},{"name":"Chugai Pharmabody Research Pte. Ltd., Singapore 138623, Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christine Xing\u2019er","family":"Koo","sequence":"additional","affiliation":[{"name":"Chugai Pharmabody Research Pte. Ltd., Singapore 138623, Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5631-3696","authenticated-orcid":false,"given":"Frannie Jiuyi","family":"Teo","sequence":"additional","affiliation":[{"name":"Singapore Immunology Network, Agency for Science, Technology and Research, Singapore 138648, Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ying Xiu","family":"Toh","sequence":"additional","affiliation":[{"name":"Singapore Immunology Network, Agency for Science, Technology and Research, Singapore 138648, Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Taku","family":"Fukuzawa","sequence":"additional","affiliation":[{"name":"Chugai Pharmaceutical Co., Ltd., Yokohama 244-8602, Japan"},{"name":"Chugai Pharmabody Research Pte. Ltd., Singapore 138623, Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6982-4492","authenticated-orcid":false,"given":"Siok Wan","family":"Gan","sequence":"additional","affiliation":[{"name":"Chugai Pharmabody Research Pte. Ltd., Singapore 138623, Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takeru","family":"Nambu","sequence":"additional","affiliation":[{"name":"Chugai Pharmaceutical Co., Ltd., Yokohama 244-8602, Japan"},{"name":"Chugai Pharmabody Research Pte. Ltd., Singapore 138623, Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6501-5196","authenticated-orcid":false,"given":"Adrian","family":"Ho","sequence":"additional","affiliation":[{"name":"Chugai Pharmabody Research Pte. Ltd., Singapore 138623, Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kiyofumi","family":"Honda","sequence":"additional","affiliation":[{"name":"Chugai Pharmaceutical Co., Ltd., Yokohama 244-8602, Japan"},{"name":"Chugai Pharmabody Research Pte. Ltd., Singapore 138623, Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tomoyuki","family":"Igawa","sequence":"additional","affiliation":[{"name":"Chugai Pharmaceutical Co., Ltd., Yokohama 244-8602, Japan"},{"name":"Chugai Pharmabody Research Pte. Ltd., Singapore 138623, Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fariyal","family":"Ahmed","sequence":"additional","affiliation":[{"name":"Singapore Immunology Network, Agency for Science, Technology and Research, Singapore 138648, Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cheng-I","family":"Wang","sequence":"additional","affiliation":[{"name":"Singapore Immunology Network, Agency for Science, Technology and Research, Singapore 138648, Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3571-0390","authenticated-orcid":false,"given":"Katja","family":"Fink","sequence":"additional","affiliation":[{"name":"Singapore Immunology Network, Agency for Science, Technology and Research, Singapore 138648, Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0476-1264","authenticated-orcid":false,"given":"Junichi","family":"Nezu","sequence":"additional","affiliation":[{"name":"Chugai Pharmaceutical Co., Ltd., Yokohama 244-8602, Japan"},{"name":"Chugai Pharmabody Research Pte. Ltd., Singapore 138623, Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,5,15]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1423","DOI":"10.1056\/NEJMra1110265","article-title":"Dengue","volume":"366","author":"Simmons","year":"2012","journal-title":"N. Engl. J. Med."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"504","DOI":"10.1038\/nature12060","article-title":"The global distribution and burden of dengue","volume":"496","author":"Bhatt","year":"2013","journal-title":"Nature"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1445","DOI":"10.1007\/s00705-013-1645-3","article-title":"Secondary infection as a risk factor for dengue hemorrhagic fever\/dengue shock syndrome: An historical perspective and role of antibody-dependent enhancement of infection","volume":"158","author":"Guzman","year":"2013","journal-title":"Arch. 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