{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,9]],"date-time":"2026-09-09T00:31:59Z","timestamp":1788913919796,"version":"build-2803163510"},"reference-count":34,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2023,4,23]],"date-time":"2023-04-23T00:00:00Z","timestamp":1682208000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82071848"],"award-info":[{"award-number":["82071848"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["2023-JC-YB-640"],"award-info":[{"award-number":["2023-JC-YB-640"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Natural Science Basic Research Plan in Shaanxi Province of China","award":["82071848"],"award-info":[{"award-number":["82071848"]}]},{"name":"Natural Science Basic Research Plan in Shaanxi Province of China","award":["2023-JC-YB-640"],"award-info":[{"award-number":["2023-JC-YB-640"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Viruses"],"abstract":"<jats:p>China is one of the main epidemic areas for hemorrhagic fever with renal syndrome (HFRS). Currently, there is no human antibody specific to Hantaan virus (HTNV) for the emergency prevention and treatment of HFRS. To prepare human antibodies with neutralizing activity, we established an anti-HTNV phage antibody library using phage display technology by transforming peripheral blood mononuclear cells (PBMCs) of patients with HFRS into B lymphoblastoid cell lines (BLCLs) and extracting cDNA from BLCLs that secreted neutralizing antibodies. Based on the phage antibody library, we screened HTNV-specific Fab antibodies with neutralizing activities. Our study provides a potential way forward for the emergency prevention of HTNV and specific treatment of HFRS.<\/jats:p>","DOI":"10.3390\/v15051034","type":"journal-article","created":{"date-parts":[[2023,4,24]],"date-time":"2023-04-24T01:35:44Z","timestamp":1682300144000},"page":"1034","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Construction of a Hantaan Virus Phage Antibody Library and Screening for Potential Neutralizing Activity"],"prefix":"10.3390","volume":"15","author":[{"given":"Zhuo","family":"Li","sequence":"first","affiliation":[{"name":"Department of Immunology, The Fourth Military Medical University, 169 Changle West Road, Xi\u2019an 710032, China"},{"name":"Department of Medical Laboratory Technology, Xi\u2019an Health School, Xi\u2019an 710054, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5557-3645","authenticated-orcid":false,"given":"Huiyuan","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Immunology, The Fourth Military Medical University, 169 Changle West Road, Xi\u2019an 710032, China"},{"name":"Department of Immunology, Medicine School, Yan\u2019an University, Yan\u2019an 716000, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaxia","family":"Yu","sequence":"additional","affiliation":[{"name":"Department of Immunology, The Fourth Military Medical University, 169 Changle West Road, Xi\u2019an 710032, China"},{"name":"Department of Immunology, Medicine School, Yan\u2019an University, Yan\u2019an 716000, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4272-857X","authenticated-orcid":false,"given":"Yusi","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Immunology, The Fourth Military Medical University, 169 Changle West Road, Xi\u2019an 710032, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lihua","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Immunology, The Fourth Military Medical University, 169 Changle West Road, Xi\u2019an 710032, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,4,23]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Brocato, R.L., and Hooper, J.W. (2019). Progress on the Prevention and Treatment of Hantavirus Disease. Viruses, 11.","DOI":"10.3390\/v11070610"},{"key":"ref_2","first-page":"1","article-title":"Hemorrhagic Fever with Renal Syndrome: Pathogenesis and Clinical Picture","volume":"6","author":"Jiang","year":"2016","journal-title":"Front. Cell. Infect. Microbiol."},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Shen, L., Sun, M., Wei, X., Bai, Y., Hu, Q., Song, S., Gao, B., Zhang, W., Liu, J., and Shao, Z. (2022). Spatiotemporal association of rapid urbanization and water-body distribution on hemorrhagic fever with renal syndrome: A case study in the city of Xi\u2019an, China. PLoS Negl. Trop. Dis., 16.","DOI":"10.1371\/journal.pntd.0010094"},{"key":"ref_4","doi-asserted-by":"crossref","unstructured":"Li, N., Li, A., Liu, Y., Wu, W., Li, C., Yu, D., Zhu, Y., Li, J., Li, D., and Wang, S. (2020). Genetic diversity and evolution of Hantaan virus in China and its neighbors. PLoS Negl. Trop. Dis., 14.","DOI":"10.1101\/2020.01.28.922724"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"749","DOI":"10.1038\/s41598-017-18819-4","article-title":"Mapping the epidemic changes and risks of hemorrhagic fever with renal syndrome in Shaanxi Province, China, 2005\u20132016","volume":"8","author":"Liang","year":"2018","journal-title":"Sci. Rep."},{"key":"ref_6","doi-asserted-by":"crossref","unstructured":"She, K., Li, C., Qi, C., Liu, T., Jia, Y., Zhu, Y., Liu, L., Wang, Z., Zhang, Y., and Li, X. (2021). Epidemiological Characteristics and Regional Risk Prediction of Hemorrhagic Fever with Renal Syndrome in Shandong Province, China. Int. J. Environ. Res. Public. Health, 18.","DOI":"10.3390\/ijerph18168495"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1680","DOI":"10.1017\/S0950268818002030","article-title":"Spatiotemporal analysis and forecasting model of hemorrhagic fever with renal syndrome in mainland China","volume":"146","author":"Sun","year":"2018","journal-title":"Epidemiol. Infect."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"9609","DOI":"10.1038\/s41598-020-66758-4","article-title":"Time series analysis of temporal trends in hemorrhagic fever with renal syndrome morbidity rate in China from 2005 to 2019","volume":"10","author":"Wang","year":"2020","journal-title":"Sci. Rep."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"3849","DOI":"10.2147\/IDR.S325787","article-title":"Estimating the Long-Term Epidemiological Trends and Seasonality of Hemorrhagic Fever with Renal Syndrome in China","volume":"14","author":"Xiao","year":"2021","journal-title":"Infect. Drug. Resist."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"531","DOI":"10.1016\/j.virs.2022.04.015","article-title":"Screening and identification of HTNV(pv) entry inhibitors with high-throughput pseudovirus-based chemiluminescence","volume":"37","author":"Wen","year":"2022","journal-title":"Virol. Sin."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"832","DOI":"10.3389\/fmicb.2020.00832","article-title":"Anti-HFRS Human IgG Produced in Transchromosomic Bovines Has Potent Hantavirus Neutralizing Activity and Is Protective in Animal Models","volume":"11","author":"Perley","year":"2020","journal-title":"Front. Microbiol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"301","DOI":"10.1186\/1743-422X-10-301","article-title":"A recombinant pseudotyped lentivirus expressing the envelope glycoprotein of hantaan virus induced protective immunity in mice","volume":"10","author":"Yu","year":"2013","journal-title":"Virol. J."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"2595","DOI":"10.1099\/vir.0.045302-0","article-title":"Identification of a novel B-cell epitope of Hantaan virus glycoprotein recognized by neutralizing 3D8 monoclonal antibody","volume":"93","author":"Yan","year":"2012","journal-title":"J. Gen. Virol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"2824","DOI":"10.1080\/21645515.2021.1908060","article-title":"Perspectives on the use and risk of adverse events associated with cytokine-storm targeting antibodies and challenges associated with development of novel monoclonal antibodies for the treatment of COVID-19 clinical cases","volume":"17","author":"Johnson","year":"2021","journal-title":"Hum. Vaccin. Immunother."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"5055","DOI":"10.1128\/AAC.00728-09","article-title":"Phase I evaluation of the safety and pharmacokinetics of a single-dose intravenous injection of a murine monoclonal antibody against Hantaan virus in healthy volunteers","volume":"53","author":"Xu","year":"2009","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"552","DOI":"10.1038\/348552a0","article-title":"Phage antibodies: Filamentous phage displaying antibody variable domains","volume":"348","author":"McCafferty","year":"1990","journal-title":"Nature"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"697876","DOI":"10.3389\/fcimb.2021.697876","article-title":"Developing Recombinant Antibodies by Phage Display Against Infectious Diseases and Toxins for Diagnostics and Therapy","volume":"11","author":"Roth","year":"2021","journal-title":"Front. Cell. Infect. Microbiol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"1315","DOI":"10.1126\/science.4001944","article-title":"Filamentous fusion phage: Novel expression vectors that display cloned antigens on the virion surface","volume":"228","author":"Smith","year":"1985","journal-title":"Science"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"99","DOI":"10.1002\/jmv.10259","article-title":"Generation of an HFRS patient-derived neutralizing recombinant antibody to Hantaan virus G1 protein and definition of the neutralizing domain","volume":"69","author":"Liang","year":"2003","journal-title":"J. Med. Virol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"64","DOI":"10.1016\/S0042-6822(02)00094-6","article-title":"Human recombinant neutralizing antibodies against hantaan virus G2 protein","volume":"308","author":"Koch","year":"2003","journal-title":"Virology"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"802","DOI":"10.1080\/21645515.2016.1253645","article-title":"The assessment of Hantaan virus-specific antibody responses after the immunization program for hemorrhagic fever with renal syndrome in northwest China","volume":"13","author":"Li","year":"2017","journal-title":"Hum. Vaccin. Immunother."},{"key":"ref_22","first-page":"20","article-title":"Application of Epstein-Barr virus-transformed B lymphoblastic cells in identification of CTL epitopes specific for Hantaan virus","volume":"25","author":"Wang","year":"2009","journal-title":"Xi Bao Yu Fen. Zi Mian Yi Xue Za Zhi"},{"key":"ref_23","doi-asserted-by":"crossref","unstructured":"Ma, Y., Wang, J., Yuan, B., Wang, M., Zhang, Y., Xu, Z., Zhang, C., Zhang, Y., Liu, B., and Yi, J. (2013). HLA-A2 and B35 restricted hantaan virus nucleoprotein CD8+ T-cell epitope-specific immune response correlates with milder disease in hemorrhagic fever with renal syndrome. PLoS Negl. Trop. Dis., 7.","DOI":"10.1371\/journal.pntd.0002076"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"420","DOI":"10.1038\/269420a0","article-title":"EB virus-induced B lymphocyte cell lines producing specific antibody","volume":"269","author":"Steinitz","year":"1977","journal-title":"Nature"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"552","DOI":"10.1016\/S0006-291X(02)02491-9","article-title":"The in vitro and in vivo protective activity of monoclonal antibodies directed against Hantaan virus: Potential application for immunotherapy and passive immunization","volume":"298","author":"Xu","year":"2002","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"185","DOI":"10.3389\/fcimb.2016.00185","article-title":"Incorporation of GM-CSF or CD40L Enhances the Immunogenicity of Hantaan Virus-Like Particles","volume":"6","author":"Cheng","year":"2016","journal-title":"Front. Cell. Infect. Microbiol."},{"key":"ref_27","doi-asserted-by":"crossref","unstructured":"Lim, C.C., Choong, Y.S., and Lim, T.S. (2019). Cognizance of Molecular Methods for the Generation of Mutagenic Phage Display Antibody Libraries for Affinity Maturation. Int. J. Mol. Sci., 20.","DOI":"10.3390\/ijms20081861"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"495","DOI":"10.3389\/fmicb.2017.00495","article-title":"Antibody Engineering for Pursuing a Healthier Future","volume":"8","author":"Saeed","year":"2017","journal-title":"Front. Microbiol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"6537","DOI":"10.1073\/pnas.92.14.6537","article-title":"Anti-melanoma antibodies from melanoma patients immunized with genetically modified autologous tumor cells: Selection of specific antibodies from single-chain Fv fusion phage libraries","volume":"92","author":"Cai","year":"1995","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"1986","DOI":"10.3389\/fimmu.2020.01986","article-title":"Phage Display Derived Monoclonal Antibodies: From Bench to Bedside","volume":"11","author":"Alfaleh","year":"2020","journal-title":"Front. Immunol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"3162","DOI":"10.1128\/jvi.64.7.3162-3170.1990","article-title":"Antigenic subunits of Hantaan virus expressed by baculovirus and vaccinia virus recombinants","volume":"64","author":"Schmaljohn","year":"1990","journal-title":"J. Virol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"269","DOI":"10.1006\/viro.1998.9586","article-title":"DNA vaccination with hantavirus M segment elicits neutralizing antibodies and protects against seoul virus infection","volume":"255","author":"Hooper","year":"1999","journal-title":"Virology"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"746","DOI":"10.1089\/vbz.2014.1650","article-title":"A glycoprotein subunit vaccine elicits a strong Rift Valley fever virus neutralizing antibody response in sheep","volume":"14","author":"Faburay","year":"2014","journal-title":"Vector Borne Zoonotic Dis."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1038\/jid.2013.521","article-title":"Antibody phage display: Technique and applications","volume":"134","author":"Hammers","year":"2014","journal-title":"J. Invest. Dermatol."}],"container-title":["Viruses"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1999-4915\/15\/5\/1034\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T19:21:29Z","timestamp":1760124089000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1999-4915\/15\/5\/1034"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,4,23]]},"references-count":34,"journal-issue":{"issue":"5","published-online":{"date-parts":[[2023,5]]}},"alternative-id":["v15051034"],"URL":"https:\/\/doi.org\/10.3390\/v15051034","relation":{},"ISSN":["1999-4915"],"issn-type":[{"value":"1999-4915","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,4,23]]}}}