{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,10]],"date-time":"2026-04-10T02:26:00Z","timestamp":1775787960692,"version":"3.50.1"},"reference-count":68,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2021,6,3]],"date-time":"2021-06-03T00:00:00Z","timestamp":1622678400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Plant Biotechnology Journal"],"published-print":{"date-parts":[[2021,10]]},"abstract":"<jats:title>Summary<\/jats:title><jats:p>Chronic infection with hepatitis C virus (HCV) remains a leading cause of liver\u2010related pathologies and a global health problem, currently affecting more than 71\u00a0million people worldwide. The development of a prophylactic vaccine is much needed to complement the effective antiviral treatment available and achieve HCV eradication. Current strategies focus on increasing the immunogenicity of the HCV envelope glycoprotein E2, the major target of virus\u2010neutralizing antibodies, by testing various expression systems or manipulating the protein conformation and the N\u2010glycosylation pattern. Here we report the first evidence of successful production of the full\u2010length HCV E2 glycoprotein in <jats:italic>Nicotiana benthamiana<\/jats:italic>, by using the <jats:italic>Agrobacterium<\/jats:italic>\u2010mediated transient expression technology. Molecular and functional analysis showed that the viral protein was correctly processed in plant cells and achieved the native folding required for binding to CD81, one of the HCV receptors. N\u2010glycan analysis of HCV\u2010E2 produced in <jats:italic>N<\/jats:italic>.\u00a0<jats:italic>benthamiana<\/jats:italic> and mammalian cells indicated host\u2010specific trimming of mannose residues and possibly, protein trafficking. Notably, the plant\u2010derived viral antigen triggered a significant immune response in vaccinated mice, characterized by the presence of antibodies with HCV\u2010neutralizing activity. Together, our study demonstrates that <jats:italic>N<\/jats:italic>.\u00a0<jats:italic>benthamiana<\/jats:italic> is a viable alternative to costly mammalian cell cultures for the expression of complex viral antigens and supports the use of plants as cost\u2010effective production platforms for the development of HCV vaccines.<\/jats:p>","DOI":"10.1111\/pbi.13631","type":"journal-article","created":{"date-parts":[[2021,5,18]],"date-time":"2021-05-18T09:06:09Z","timestamp":1621328769000},"page":"2027-2039","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":15,"title":["Hepatitis C virus E2 envelope glycoprotein produced in <i>Nicotiana benthamiana<\/i> triggers humoral response with virus\u2010neutralizing activity in vaccinated 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