title: Protection conferred by recombinant Yersinia pestis antigens produced by a rapid and highly scalable plant expression system.
abstract: Plague is still an endemic disease in different regions of the world. Increasing reports of incidence, the discovery of antibiotic resistance strains, and concern about a potential use of the causative bacteria Yersinia pestis as an agent of biological warfare have highlighted the need for a safe, efficacious, and rapidly producible vaccine. The use of F1 and V antigens and the derived protein fusion F1-V has shown great potential as a protective vaccine in animal studies. Plants have been extensively studied for the production of pharmaceutical proteins as an inexpensive and scalable alternative to common expression systems. In the current study the recombinant plague antigens F1, V, and fusion protein F1-V were produced by transient expression in Nicotiana benthamiana by using a deconstructed tobacco mosaic virus-based system that allowed very rapid and extremely high levels of expression. All of the plant-derived purified antigens, administered s.c. to guinea pigs, generated systemic immune responses and provided protection against an aerosol challenge of virulent Y. pestis.
authors.affiliation: Biodesign Institute, Arizona State University, Tempe, AZ 85287-5401, USA.
authors.forename: Luca
authors.initials: L
authors.lastname: Santi
authors.forename: Anatoli
authors.initials: A
authors.lastname: Giritch
authors.forename: Chad J
authors.initials: CJ
authors.lastname: Roy
authors.forename: Sylvestre
authors.initials: S
authors.lastname: Marillonnet
authors.forename: Victor
authors.initials: V
authors.lastname: Klimyuk
authors.forename: Yuri
authors.initials: Y
authors.lastname: Gleba
authors.forename: Robert
authors.initials: R
authors.lastname: Webb
authors.forename: Charles J
authors.initials: CJ
authors.lastname: Arntzen
authors.forename: Hugh S
authors.initials: HS
authors.lastname: Mason
mesh_terms: D000336:Aerosols; D000818:Animals; D000942:Antigens, Bacterial / Q000096:biosynthesis; D001426:Bacterial Proteins / Q000096:biosynthesis; D015153:Blotting, Western; D002852:Chromatography, Ion Exchange; D004591:Electrophoresis, Polyacrylamide Gel; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005818:Genetic Engineering; D005822:Genetic Vectors / Q000378:metabolism; D006168:Guinea Pigs; D007074:Immunoglobulin G / Q000378:metabolism; D008969:Molecular Sequence Data; D018515:Plant Leaves; D010944:Plants / Q000378:metabolism*; D052899:Pore Forming Cytotoxic Proteins; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D011994:Recombinant Proteins / Q000737:chemistry*; D012231:Rhizobium / Q000378:metabolism; D013997:Time Factors; D014026:Nicotiana; D014027:Tobacco Mosaic Virus / Q000378:metabolism; D015010:Yersinia pestis / Q000378:metabolism*
chemical_list: D000336:Aerosols; D000942:Antigens, Bacterial; D001426:Bacterial Proteins; D007074:Immunoglobulin G; C043908:LcrV protein, Yersinia; D052899:Pore Forming Cytotoxic Proteins; D011993:Recombinant Fusion Proteins; D011994:Recombinant Proteins; C086725:caf1 protein, Yersinia pestis