{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,29]],"date-time":"2026-05-29T14:53:04Z","timestamp":1780066384846,"version":"3.54.0"},"reference-count":60,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2020,2,2]],"date-time":"2020-02-02T00:00:00Z","timestamp":1580601600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Viruses"],"abstract":"<jats:p>Although seasonal influenza vaccines block most predominant influenza types and subtypes, humans still remain vulnerable to waves of seasonal and new potential pandemic influenza viruses for which no immunity may exist because of viral antigenic drift and\/or shift. Previously, we described a human monoclonal antibody (hMAb), KPF1, which was produced in human embryonic kidney 293T cells (KPF1-HEK) with broad and potent neutralizing activity against H1N1 influenza A viruses (IAV) in vitro, and prophylactic and therapeutic activities in vivo. In this study, we produced hMAb KPF1 in tobacco plants (KPF1-Antx) and demonstrated how the plant-produced KPF1-Antx hMAb possesses similar biological activity compared with the mammalian-produced KPF1-HEK hMAb. KPF1-Antx hMAb showed broad binding to recombinant HA proteins and H1N1 IAV, including A\/California\/04\/2009 (pH1N1) in vitro, which was comparable to that observed with KPF1-HEK hMAb. Importantly, prophylactic administration of KPF1-Antx hMAb to guinea pigs prevented pH1N1 infection and transmission in both prophylactic and therapeutic experiments, substantiating its clinical potential to prevent and treat H1N1 infections. Collectively, this study demonstrated, for the first time, a plant-produced influenza hMAb with in vitro and in vivo activity against influenza virus. Because of the many advantages of plant-produced hMAbs, such as rapid batch production, low cost, and the absence of mammalian cell products, they represent an alternative strategy for the production of immunotherapeutics for the treatment of influenza viral infections, including emerging seasonal and\/or pandemic strains.<\/jats:p>","DOI":"10.3390\/v12020167","type":"journal-article","created":{"date-parts":[[2020,2,3]],"date-time":"2020-02-03T11:28:31Z","timestamp":1580729311000},"page":"167","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["A Broad and Potent H1-Specific Human Monoclonal Antibody Produced in Plants Prevents Influenza Virus Infection and Transmission in Guinea Pigs"],"prefix":"10.3390","volume":"12","author":[{"given":"Jun-Gyu","family":"Park","sequence":"first","affiliation":[{"name":"Department of Microbiology and Immunology, University of Rochester Medical Center, 601 Elmwood Avenue, Rochester, NY 14642, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chengjin","family":"Ye","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, University of Rochester Medical Center, 601 Elmwood Avenue, Rochester, NY 14642, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael S.","family":"Piepenbrink","sequence":"additional","affiliation":[{"name":"Department of Medicine, Division of Infectious Diseases, University of Alabama at Birmingham 845 19th Street South, Birmingham, AL 35294, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aitor","family":"Nogales","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, University of Rochester Medical Center, 601 Elmwood Avenue, Rochester, NY 14642, USA"},{"name":"Instituto Nacional de Investigaci\u00f3n y Tecnolog\u00eda Agraria y Alimentaria, Centro de Investigaci\u00f3n en Sanidad Animal (INIA-CISA), 28130 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haifeng","family":"Wang","sequence":"additional","affiliation":[{"name":"PlantForm Corporation, 1920 Yonge St., Suite 200, Toronto, ON M4S 3E2, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Shuen","sequence":"additional","affiliation":[{"name":"PlantForm Corporation, 1920 Yonge St., Suite 200, Toronto, ON M4S 3E2, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ashley J.","family":"Meyers","sequence":"additional","affiliation":[{"name":"AntoXa Corporation, 1920 Yonge St., Suite 200, Toronto, ON M4S 3E2, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luis","family":"Martinez-Sobrido","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, University of Rochester Medical Center, 601 Elmwood Avenue, Rochester, NY 14642, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8069-0272","authenticated-orcid":false,"given":"James J.","family":"Kobie","sequence":"additional","affiliation":[{"name":"Department of Medicine, Division of Infectious Diseases, University of Alabama at Birmingham 845 19th Street South, Birmingham, AL 35294, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2020,2,2]]},"reference":[{"key":"ref_1","unstructured":"Knipe, D.M., Howley, P.M., Cohen, J.I., Griffin, D.E., Lamb, R.A., Martin, M.A., Racaniello, V.R., and Roizman, B. (2013). Fields Virology, Wolters Kluwer Health. [6th  ed.]."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"209","DOI":"10.1038\/nature02746","article-title":"Genesis of a highly pathogenic and potentially pandemic H5N1 influenza virus in eastern Asia","volume":"430","author":"Li","year":"2004","journal-title":"Nature"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1156","DOI":"10.1016\/j.vaccine.2009.11.043","article-title":"Writing Committee of the World Health Organization Consultation on Northern Hemisphere Influenza Vaccine Composition, f. Epidemiological, antigenic and genetic characteristics of seasonal influenza A(H1N1), A(H3N2) and B influenza viruses: Basis for the WHO recommendation on the composition of influenza vaccines for use in the 2009\u20132010 northern hemisphere season","volume":"28","author":"Barr","year":"2010","journal-title":"Vaccine"},{"key":"ref_4","doi-asserted-by":"crossref","unstructured":"Clark, A.M., DeDiego, M.L., Anderson, C.S., Wang, J., Yang, H., Nogales, A., Martinez-Sobrido, L., Zand, M.S., Sangster, M.Y., and Topham, D.J. (2017). Antigenicity of the 2015\u20132016 seasonal H1N1 human influenza virus HA and NA proteins. PLoS ONE, 12.","DOI":"10.1371\/journal.pone.0188267"},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"Federici, C., Cavazza, M., Costa, F., and Jommi, C. (2018). Health care costs of influenza-related episodes in high income countries: A systematic review. PLoS ONE, 13.","DOI":"10.1371\/journal.pone.0202787"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"5086","DOI":"10.1016\/j.vaccine.2007.03.046","article-title":"The annual impact of seasonal influenza in the US: Measuring disease burden and costs","volume":"25","author":"Molinari","year":"2007","journal-title":"Vaccine"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"234","DOI":"10.1016\/j.virol.2015.03.009","article-title":"Transmission of influenza A viruses","volume":"479\u2013480","author":"Neumann","year":"2015","journal-title":"Virology"},{"key":"ref_8","first-page":"137","article-title":"Avian influenza virus transmission to mammals","volume":"385","author":"Herfst","year":"2014","journal-title":"Curr. Top. Microbiol. Immunol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1015","DOI":"10.1038\/nrd2175","article-title":"Antiviral agents active against influenza A viruses","volume":"5","year":"2006","journal-title":"Nat. Rev. Drug Discov."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"104545","DOI":"10.1016\/j.antiviral.2019.104545","article-title":"Antivirals targeting the polymerase complex of influenza viruses","volume":"169","author":"Mifsud","year":"2019","journal-title":"Antiviral Res."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"14","DOI":"10.1016\/j.coviro.2019.01.006","article-title":"Baloxavir marboxil: The new influenza drug on the market","volume":"35","author":"Shaw","year":"2019","journal-title":"Curr. Opin. Virol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1580","DOI":"10.1080\/21505594.2017.1365216","article-title":"Novel Influenza D virus: Epidemiology, pathology, evolution and biological characteristics","volume":"8","author":"Su","year":"2017","journal-title":"Virulence"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"10778","DOI":"10.1128\/JVI.01440-14","article-title":"Influenza A and B virus intertypic reassortment through compatible viral packaging signals","volume":"88","author":"Baker","year":"2014","journal-title":"J. Virol."},{"key":"ref_14","unstructured":"(2019, December 23). Influenza Research Database. Available online: https:\/\/www.fludb.org\/brc\/home.spg?decorator=influenza."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"553","DOI":"10.1146\/annurev.micro.59.030804.121059","article-title":"The origins of new pandemic viruses: The acquisition of new host ranges by canine parvovirus and influenza A viruses","volume":"59","author":"Parrish","year":"2005","journal-title":"Annu Rev. Microbiol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"2990","DOI":"10.1128\/JVI.03146-14","article-title":"Influenza virus reservoirs and intermediate hosts: Dogs, horses, and new possibilities for influenza virus exposure of humans","volume":"89","author":"Parrish","year":"2015","journal-title":"J. Virol."},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Tong, S., Zhu, X., Li, Y., Shi, M., Zhang, J., Bourgeois, M., Yang, H., Chen, X., Recuenco, S., and Gomez, J. (2013). New world bats harbor diverse influenza A viruses. PLoS Pathog., 9.","DOI":"10.1371\/journal.ppat.1003657"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"4269","DOI":"10.1073\/pnas.1116200109","article-title":"A distinct lineage of influenza A virus from bats","volume":"109","author":"Tong","year":"2012","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"4374","DOI":"10.1038\/s41598-018-22307-8","article-title":"A Highly Potent and Broadly Neutralizing H1 Influenza-Specific Human Monoclonal Antibody","volume":"8","author":"Nogales","year":"2018","journal-title":"Sci. Rep."},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"Blanco-Lobo, P., Nogales, A., Rodriguez, L., and Martinez-Sobrido, L. (2019). Novel Approaches for The Development of Live Attenuated Influenza Vaccines. Viruses, 11.","DOI":"10.3390\/v11020190"},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Martinez-Sobrido, L., Peersen, O., and Nogales, A. (2018). Temperature Sensitive Mutations in Influenza A Viral Ribonucleoprotein Complex Responsible for the Attenuation of the Live Attenuated Influenza Vaccine. Viruses, 10.","DOI":"10.3390\/v10100560"},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"Nogales, A., and Martinez-Sobrido, L. (2016). Reverse Genetics Approaches for the Development of Influenza Vaccines. Int. J. Mol. Sci., 18.","DOI":"10.3390\/ijms18010020"},{"key":"ref_23","doi-asserted-by":"crossref","unstructured":"Takashita, E., Kawakami, C., Morita, H., Ogawa, R., Fujisaki, S., Shirakura, M., Miura, H., Nakamura, K., Kishida, N., and Kuwahara, T. (2019). Detection of influenza A(H3N2) viruses exhibiting reduced susceptibility to the novel cap-dependent endonuclease inhibitor baloxavir in Japan, December 2018. Euro. Surveill., 24.","DOI":"10.2807\/1560-7917.ES.2019.24.3.1800698"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"74","DOI":"10.1016\/j.jiph.2009.04.004","article-title":"Oseltamivir resistance mutation N294S in human influenza A(H5N1) virus in Egypt","volume":"2","author":"Earhart","year":"2009","journal-title":"J. Infect. Public Health"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"9633","DOI":"10.1038\/s41598-018-27890-4","article-title":"Characterization of influenza virus variants induced by treatment with the endonuclease inhibitor baloxavir marboxil","volume":"8","author":"Omoto","year":"2018","journal-title":"Sci. Rep."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"471","DOI":"10.2165\/00003088-199937060-00003","article-title":"Clinical pharmacokinetics of the prodrug oseltamivir and its active metabolite Ro 64-0802","volume":"37","author":"He","year":"1999","journal-title":"Clin. Pharmacokinet."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"ii5","DOI":"10.1093\/jac\/dkq015","article-title":"Pharmacokinetics of oseltamivir: An oral antiviral for the treatment and prophylaxis of influenza in diverse populations","volume":"65","author":"Davies","year":"2010","journal-title":"J. Antimicrob. Chemother."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"454","DOI":"10.7326\/0003-4819-94-4-454","article-title":"Pharmacokinetics of amantadine hydrochloride in subjects with normal and impaired renal function","volume":"94","author":"Horadam","year":"1981","journal-title":"Ann. Intern. Med."},{"key":"ref_29","first-page":"9","article-title":"Xofluza (Baloxavir Marboxil) for the Treatment Of Acute Uncomplicated Influenza","volume":"44","author":"Ng","year":"2019","journal-title":"P T"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"2429","DOI":"10.2174\/1381612054367508","article-title":"Secretory IgA antibodies from plants","volume":"11","author":"Wycoff","year":"2005","journal-title":"Curr. Pharm. Des."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"53","DOI":"10.1111\/pbi.12006","article-title":"Comparative in vitro and experimental in vivo studies of the anti-epidermal growth factor receptor antibody nimotuzumab and its aglycosylated form produced in transgenic tobacco plants","volume":"11","author":"Rodriguez","year":"2013","journal-title":"Plant. Biotechnol. J."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"76","DOI":"10.1038\/342076a0","article-title":"Production of antibodies in transgenic plants","volume":"342","author":"Hiatt","year":"1989","journal-title":"Nature"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"95","DOI":"10.1111\/j.1467-7652.2011.00649.x","article-title":"Robust production of virus-like particles and monoclonal antibodies with geminiviral replicon vectors in lettuce","volume":"10","author":"Lai","year":"2012","journal-title":"Plant. Biotechnol. J."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"3499","DOI":"10.1128\/AEM.66.8.3499-3505.2000","article-title":"Expression of a functional antizearalenone single-chain Fv antibody in transgenic Arabidopsis plants","volume":"66","author":"Yuan","year":"2000","journal-title":"Appl. Environ. Microbiol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"346","DOI":"10.1128\/CVI.00620-15","article-title":"Potent In Vitro and In Vivo Activity of Plantibody Specific for Porphyromonas gingivalis FimA","volume":"23","author":"Choi","year":"2016","journal-title":"Clin. Vaccine Immunol."},{"key":"ref_36","doi-asserted-by":"crossref","unstructured":"Nakanishi, K., Narimatsu, S., Ichikawa, S., Tobisawa, Y., Kurohane, K., Niwa, Y., Kobayashi, H., and Imai, Y. (2013). Production of hybrid-IgG\/IgA plantibodies with neutralizing activity against Shiga toxin 1. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0080712"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"9747549","DOI":"10.1155\/2018\/9747549","article-title":"Evolution of Therapeutic Antibodies, Influenza Virus Biology, Influenza, and Influenza Immunotherapy","volume":"2018","author":"Chaisri","year":"2018","journal-title":"Biomed. Res. Int."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"777","DOI":"10.1128\/CVI.00003-14","article-title":"Chimeric plantibody passively protects mice against aerosolized ricin challenge","volume":"21","author":"Sully","year":"2014","journal-title":"Clin. Vaccine Immunol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"e1774","DOI":"10.21859\/ijb.1774","article-title":"Transient Expression of Biologically Active Anti-rabies Virus Monoclonal Antibody in Tobacco Leaves","volume":"16","author":"Shafaghi","year":"2018","journal-title":"Iran. J. Biotechnol."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"e00314","DOI":"10.1016\/j.btre.2019.e00314","article-title":"Transient plant production of Salmonella Typhimurium diagnostic antibodies","volume":"21","author":"Kopertekh","year":"2019","journal-title":"Biotechnol. Rep. (Amst)"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"45843","DOI":"10.1038\/srep45843","article-title":"Protection of Human Colon Cells from Shiga Toxin by Plant-based Recombinant Secretory IgA","volume":"7","author":"Nakanishi","year":"2017","journal-title":"Sci. Rep."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"2419","DOI":"10.1073\/pnas.0914503107","article-title":"Monoclonal antibody produced in plants efficiently treats West Nile virus infection in mice","volume":"107","author":"Lai","year":"2010","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"1412","DOI":"10.1055\/s-0043-112344","article-title":"Rapid Transient Production of a Monoclonal Antibody Neutralizing the Porcine Epidemic Diarrhea Virus (PEDV) in Nicotiana benthamiana and Lactuca sativa","volume":"83","author":"Rattanapisit","year":"2017","journal-title":"Planta Med."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"897","DOI":"10.1007\/s11248-015-9890-8","article-title":"Tobacco seeds as efficient production platform for a biologically active anti-HBsAg monoclonal antibody","volume":"24","year":"2015","journal-title":"Transgenic. Res."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"295","DOI":"10.1093\/bfgp\/ely020","article-title":"Vaccine and antibody production in plants: Developments and computational tools","volume":"17","author":"Dubey","year":"2018","journal-title":"Brief. Funct. Genomics"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"18030","DOI":"10.1073\/pnas.1213709109","article-title":"Delayed treatment of Ebola virus infection with plant-derived monoclonal antibodies provides protection in rhesus macaques","volume":"109","author":"Olinger","year":"2012","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"e00032-19","DOI":"10.1128\/JVI.00032-19","article-title":"A novel fluorescent and bioluminescent Bi-Reporter influenza A virus (BIRFLU) to evaluate viral infections","volume":"93","author":"Nogales","year":"2019","journal-title":"J. Virol."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"206","DOI":"10.1016\/j.virol.2014.12.006","article-title":"Replication-competent influenza A viruses expressing a red fluorescent protein","volume":"476","author":"Nogales","year":"2015","journal-title":"Virology"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"e00720-17","DOI":"10.1128\/JVI.00720-17","article-title":"Interplay of PA-X and NS1 Proteins in Replication and Pathogenesis of a Temperature-Sensitive 2009 Pandemic H1N1 Influenza A Virus","volume":"91","author":"Nogales","year":"2017","journal-title":"J. Virol."},{"key":"ref_50","unstructured":"Wing-Fai Cheung, H.W., Rebecca, P., Hirak, S., Warren, W., and Wakarchuk, D.C.a.M.D.M. (2020). Development of fine-control expression vectors for post-translational modification of therapeutic proteins in plants. Mol. Biotechnol., Submitted."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"1700","DOI":"10.1111\/pbi.12906","article-title":"An oligosaccharyltransferase from Leishmania major increases the N-glycan occupancy on recombinant glycoproteins produced in Nicotiana benthamiana","volume":"16","author":"Castilho","year":"2018","journal-title":"Plant. Biotechnol. J."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"389","DOI":"10.1007\/978-1-61779-974-7_23","article-title":"Transient and stable expression of antibodies in Nicotiana species","volume":"907","author":"Garabagi","year":"2012","journal-title":"Methods Mol. Biol."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"378","DOI":"10.1002\/ar.22641","article-title":"Quantitative analysis of histological staining and fluorescence using ImageJ","volume":"296","author":"Jensen","year":"2013","journal-title":"Anat Rec. (Hoboken)"},{"key":"ref_54","unstructured":"National Research Council (U.S.). Committee for the Update of the Guide for the Care and Use of Laboratory Animals (2011). Guide for the Care and Use of Laboratory Animals, National Academies Press. [8th ed.]."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"93","DOI":"10.1016\/j.virol.2014.10.003","article-title":"Live attenuated influenza A virus vaccine protects against A(H1N1)pdm09 heterologous challenge without vaccine associated enhanced respiratory disease","volume":"471\u2013473","author":"Gauger","year":"2014","journal-title":"Virology"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"5014","DOI":"10.4049\/jimmunol.1502632","article-title":"Aerosol Delivery of a Candidate Universal Influenza Vaccine Reduces Viral Load in Pigs Challenged with Pandemic H1N1 Virus","volume":"196","author":"Morgan","year":"2016","journal-title":"J. Immunol."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"1169","DOI":"10.1111\/pbi.12452","article-title":"Leaf proteome rebalancing in Nicotiana benthamiana for upstream enrichment of a transiently expressed recombinant protein","volume":"13","author":"Robert","year":"2015","journal-title":"Plant. Biotechnol. J."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"1845","DOI":"10.1016\/S0140-6736(00)02288-1","article-title":"Efficacy and safety of oseltamivir in treatment of acute influenza: A randomised controlled trial. Neuraminidase Inhibitor Flu Treatment Investigator Group","volume":"355","author":"Nicholson","year":"2000","journal-title":"Lancet"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"ofv100","DOI":"10.1093\/ofid\/ofv100","article-title":"Impact of Late Oseltamivir Treatment on Influenza Symptoms in the Outpatient Setting: Results of a Randomized Trial","volume":"2","author":"McLean","year":"2015","journal-title":"Open Forum Infect. Dis."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"564","DOI":"10.1111\/j.1467-7652.2009.00497.x","article-title":"Plant-specific glycosylation patterns in the context of therapeutic protein production","volume":"8","author":"Gomord","year":"2010","journal-title":"Plant. Biotechnol. J."}],"container-title":["Viruses"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1999-4915\/12\/2\/167\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T08:53:58Z","timestamp":1760172838000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1999-4915\/12\/2\/167"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,2,2]]},"references-count":60,"journal-issue":{"issue":"2","published-online":{"date-parts":[[2020,2]]}},"alternative-id":["v12020167"],"URL":"https:\/\/doi.org\/10.3390\/v12020167","relation":{"has-preprint":[{"id-type":"doi","id":"10.1101\/2020.01.13.902841","asserted-by":"object"}]},"ISSN":["1999-4915"],"issn-type":[{"value":"1999-4915","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,2,2]]}}}