title: Norovirus Narita 104 virus-like particles expressed in Nicotiana benthamiana induce serum and mucosal immune responses.
abstract: Narita 104 virus is a human pathogen belonging to the norovirus (family Caliciviridae) genogroup II. Noroviruses cause epidemic gastroenteritis worldwide. To explore the potential of developing a plant-based vaccine, a plant optimized gene encoding Narita 104 virus capsid protein (NaVCP) was expressed transiently in Nicotiana benthamiana using a tobacco mosaic virus expression system. NaVCP accumulated up to approximately 0.3 mg/g fresh weight of leaf at 4 days postinfection. Initiation of hypersensitive response-like symptoms followed by tissue necrosis necessitated a brief infection time and was a significant factor limiting expression. Transmission electron microscopy of plant-derived NaVCP confirmed the presence of fully assembled virus-like particles (VLPs). In this study, an optimized method to express and partially purify NaVCP is described. Further, partially purified NaVCP was used to immunize mice by intranasal delivery and generated significant mucosal and serum antibody responses. Thus, plant-derived Narita 104 VLPs have potential for use as a candidate subunit vaccine or as a component of a multivalent subunit vaccine, along with other genotype-specific plant-derived VLPs.
authors.affiliation: Center for Infectious Diseases and Vaccinology (CIDV), The Biodesign Institute at Arizona State University, 1001 South McAllister Avenue, Tempe, AZ 85287, USA ; The School of Life Sciences, 1001 South McAllister Avenue, Tempe, AZ 85287, USA.
authors.forename: Lolita George
authors.initials: LG
authors.lastname: Mathew
authors.affiliation: Center for Infectious Diseases and Vaccinology (CIDV), The Biodesign Institute at Arizona State University, 1001 South McAllister Avenue, Tempe, AZ 85287, USA ; Department of Basic Medical Sciences, University of Arizona College of Medicine-Phoenix, 425 N. 5th Street, Phoenix, AZ 85004, USA.
authors.forename: Melissa M
authors.initials: MM
authors.lastname: Herbst-Kralovetz
authors.affiliation: Center for Infectious Diseases and Vaccinology (CIDV), The Biodesign Institute at Arizona State University, 1001 South McAllister Avenue, Tempe, AZ 85287, USA ; The School of Life Sciences, 1001 South McAllister Avenue, Tempe, AZ 85287, USA.
authors.forename: Hugh S
authors.initials: HS
authors.lastname: Mason
mesh_terms: D000818:Animals; D036022:Capsid Proteins / Q000096:biosynthesis* / Q000235:genetics; D005759:Gastroenteritis / Q000235:genetics / Q000473:pathology / Q000821:virology*; D018506:Gene Expression Regulation, Plant; D015967:Gene Expression Regulation, Viral; D006801:Humans; D007111:Immunity, Cellular / Q000235:genetics*; D051379:Mice; D029322:Norovirus / Q000235:genetics* / Q000254:growth & development; D014026:Nicotiana / Q000235:genetics
chemical_list: D036022:Capsid Proteins