{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T08:21:44Z","timestamp":1790842904207,"version":"4.1.0"},"reference-count":33,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2022,9,6]],"date-time":"2022-09-06T00:00:00Z","timestamp":1662422400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2022,9,6]],"date-time":"2022-09-06T00:00:00Z","timestamp":1662422400000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Journal of Medical Virology"],"published-print":{"date-parts":[[2023,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>The discovery of broadly neutralizing monoclonal antibodies against influenza viruses has raised hope for the successful development of new antiviral drugs. However, due to the speed and variety of mutations in influenza viruses, single\u2010component antibodies that recognize specific epitopes are susceptible to viral escape and have limited efficacy when administration is delayed. Hence, it is necessary to develop alternative strategies with better antiviral activity. Influenza B virus infection can cause severe illness in children and the elderly. Commonly used anti\u2010influenza drugs have low clinical efficacy against influenza B virus. In this study, we investigated the antiviral efficacy of combinations of representative monoclonal antibodies targeting different antigenic epitopes against the influenza B virus. We found that combinations of antibodies recognizing the hemagglutinin (HA) head and stem regions showed a stronger neutralizing activity than single antibodies and other antibody combinations in vitro. In addition, we found that pair\u2010wise combinations of antibodies recognizing the HA head region, HA stem region, and neuraminidase enzyme\u2010activated region showed superior antiviral activity than single antibodies in both mouse and ferret in vivo protection assays. Notably, these antibody combinations still displayed good antiviral efficacy when treatment was delayed. Mechanistic studies further revealed that combining antibodies recognizing different epitope regions resulted in extremely strong antibody\u2010dependent cell\u2010mediated cytotoxicity, which may partly explain their superior antiviral effects. Together, the findings of this study provide new avenues for the development of better antiviral drugs and vaccines against influenza viruses.<\/jats:p>","DOI":"10.1002\/jmv.28106","type":"journal-article","created":{"date-parts":[[2022,8,30]],"date-time":"2022-08-30T06:08:19Z","timestamp":1661839699000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["Broadly neutralizing antibodies recognizing different antigenic epitopes act synergistically against the influenza B virus"],"prefix":"10.1002","volume":"95","author":[{"given":"Linlin","family":"Zhai","sequence":"first","affiliation":[{"name":"BSL\u20103 Laboratory (Guangdong), Guangdong Provincial Key Laboratory of Tropical Disease Research, School of Public Health Southern Medical University Guangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Limin","family":"Zhang","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, National Institute of Diagnostics and Vaccine Development in Infectious Diseases, School of Life Sciences, School of Public Health Xiamen University Xiamen China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yushan","family":"Jiang","sequence":"additional","affiliation":[{"name":"BSL\u20103 Laboratory (Guangdong), Guangdong Provincial Key Laboratory of Tropical Disease Research, School of Public Health Southern Medical University Guangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Baisheng","family":"Li","sequence":"additional","affiliation":[{"name":"Provincial Center for Disease Control and Prevention Guangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Minghui","family":"Yang","sequence":"additional","affiliation":[{"name":"Advanced Research Institute of Multidisciplinary Sciences, Beijing Institute of Technology Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Khrustalev Vladislav","family":"Victorovich","sequence":"additional","affiliation":[{"name":"Department of General Chemistry Belarusian State Medical University Minsk Belarus"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Khrustaleva Tatyana","family":"Aleksandrovna","sequence":"additional","affiliation":[{"name":"Biochemical Group of the Multidisciplinary Diagnostic Laboratory, Institute of Physiology of the National Academy of Sciences of Belarus Minsk Belarus"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mengjun","family":"Li","sequence":"additional","affiliation":[{"name":"BSL\u20103 Laboratory (Guangdong), Guangdong Provincial Key Laboratory of Tropical Disease Research, School of Public Health Southern Medical University Guangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuelin","family":"Wang","sequence":"additional","affiliation":[{"name":"BSL\u20103 Laboratory (Guangdong), Guangdong Provincial Key Laboratory of Tropical Disease Research, School of Public Health Southern Medical University Guangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dong","family":"Huang","sequence":"additional","affiliation":[{"name":"BSL\u20103 Laboratory (Guangdong), Guangdong Provincial Key Laboratory of Tropical Disease Research, School of Public Health Southern Medical University Guangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhujun","family":"Zeng","sequence":"additional","affiliation":[{"name":"BSL\u20103 Laboratory (Guangdong), Guangdong Provincial Key Laboratory of Tropical Disease Research, School of Public Health Southern Medical University Guangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zuning","family":"Ren","sequence":"additional","affiliation":[{"name":"BSL\u20103 Laboratory (Guangdong), Guangdong Provincial Key Laboratory of Tropical Disease Research, School of Public Health Southern Medical University Guangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hua","family":"Cao","sequence":"additional","affiliation":[{"name":"The 3rd Department of Infectious Diseases The Third People's Hospital of Shenzhen Shenzhen Guangdong China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Li","family":"Zhu","sequence":"additional","affiliation":[{"name":"BSL\u20103 Laboratory (Guangdong), Guangdong Provincial Key Laboratory of Tropical Disease Research, School of Public Health Southern Medical University Guangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qinghua","family":"Wu","sequence":"additional","affiliation":[{"name":"BSL\u20103 Laboratory (Guangdong), Guangdong Provincial Key Laboratory of Tropical Disease Research, School of Public Health Southern Medical University Guangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Weiwei","family":"Xiao","sequence":"additional","affiliation":[{"name":"BSL\u20103 Laboratory (Guangdong), Guangdong Provincial Key Laboratory of Tropical Disease Research, School of Public Health Southern Medical University Guangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bao","family":"Zhang","sequence":"additional","affiliation":[{"name":"BSL\u20103 Laboratory (Guangdong), Guangdong Provincial Key Laboratory of Tropical Disease Research, School of Public Health Southern Medical University Guangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chengsong","family":"Wan","sequence":"additional","affiliation":[{"name":"BSL\u20103 Laboratory (Guangdong), Guangdong Provincial Key Laboratory of Tropical Disease Research, School of Public Health Southern Medical University Guangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fuxiang","family":"Wang","sequence":"additional","affiliation":[{"name":"The 3rd Department of Infectious Diseases The Third People's Hospital of Shenzhen Shenzhen Guangdong China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ningshao","family":"Xia","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, National Institute of Diagnostics and Vaccine Development in Infectious Diseases, School of Life Sciences, School of Public Health Xiamen University Xiamen China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei","family":"Zhao","sequence":"additional","affiliation":[{"name":"BSL\u20103 Laboratory (Guangdong), Guangdong Provincial Key Laboratory of Tropical Disease Research, School of Public Health Southern Medical University Guangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9591-634X","authenticated-orcid":false,"given":"Yixin","family":"Chen","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, National Institute of Diagnostics and Vaccine Development in Infectious Diseases, School of Life Sciences, School of Public Health Xiamen University Xiamen China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8607-3750","authenticated-orcid":false,"given":"Chenguang","family":"Shen","sequence":"additional","affiliation":[{"name":"BSL\u20103 Laboratory (Guangdong), Guangdong Provincial Key Laboratory of Tropical Disease Research, School of Public Health Southern Medical University Guangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2022,9,6]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/d41586-019-02750-x"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(17)33293-2"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41572-018-0002-y"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(17)30129-0"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1111\/nyas.12462"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jmb.2017.06.015"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.78.22.12665-12667.2004"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.3390\/v6062465"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.coi.2018.03.025"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1222908"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2020.08.015"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.03562-13"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.7150\/thno.28434"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41591-020-0937-x"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.2112887119"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa2035002"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.aam5752"},{"key":"e_1_2_9_19_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1003150"},{"key":"e_1_2_9_20_1","doi-asserted-by":"publisher","DOI":"10.1155\/2018\/8724549"},{"key":"e_1_2_9_21_1","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.aad0522"},{"key":"e_1_2_9_22_1","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.00273-13"},{"key":"e_1_2_9_23_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-020-20789-7"},{"key":"e_1_2_9_24_1","doi-asserted-by":"publisher","DOI":"10.1542\/peds.2017-2918"},{"key":"e_1_2_9_25_1","doi-asserted-by":"publisher","DOI":"10.1007\/s40520-019-01279-3"},{"key":"e_1_2_9_26_1","doi-asserted-by":"publisher","DOI":"10.1097\/MOP.0000000000000495"},{"key":"e_1_2_9_27_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa2024848"},{"key":"e_1_2_9_28_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.antiviral.2022.105281"},{"key":"e_1_2_9_29_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.antiviral.2020.104718"},{"key":"e_1_2_9_30_1","doi-asserted-by":"publisher","DOI":"10.1093\/cid\/ciz904"},{"key":"e_1_2_9_31_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2020.01.001"},{"key":"e_1_2_9_32_1","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.00491-18"},{"key":"e_1_2_9_33_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa2031738"},{"key":"e_1_2_9_34_1","doi-asserted-by":"publisher","DOI":"10.1128\/mBio.03080-19"}],"container-title":["Journal of Medical Virology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/jmv.28106","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/jmv.28106","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/jmv.28106","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,3,8]],"date-time":"2026-03-08T08:41:50Z","timestamp":1772959310000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/jmv.28106"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,9,6]]},"references-count":33,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2023,1]]}},"alternative-id":["10.1002\/jmv.28106"],"URL":"https:\/\/doi.org\/10.1002\/jmv.28106","archive":["Portico"],"relation":{},"ISSN":["0146-6615","1096-9071"],"issn-type":[{"value":"0146-6615","type":"print"},{"value":"1096-9071","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,9,6]]},"assertion":[{"value":"2022-07-03","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2022-08-27","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2022-09-06","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e28106"}}