title: Novel 6xHis tagged foot-and-mouth disease virus vaccine bound to nanolipoprotein adjuvant via metal ions provides antigenic distinction and effective protective immunity.
abstract: Here, we engineered two FMD viruses with histidine residues inserted into or fused to the FMDV capsid. Both 6xHis viruses exhibited growth kinetics, plaque morphologies and antigenic characteristics similar to wild-type virus. The 6xHis tag allowed one-step purification of the mutant virions by Co(2+) affinity columns. Electron microscopy and biochemical assays showed that the 6xHis FMDVs readily assembled into antigen: adjuvant complexes in solution, by conjugating with Ni(2+)-chelated nanolipoprotein and monophosphoryl lipid A adjuvant (MPLA:NiNLP). Animals Immunized with the inactivated 6xHis-FMDV:MPLA:NiNLP vaccine acquired enhanced protective immunity against FMDV challenge compared to virions alone. Induction of anti-6xHis and anti-FMDV neutralizing antibodies in the immunized animals could be exploited in the differentiation of vaccinated from infected animals needed for the improvement of FMD control measures. The novel marker vaccine/nanolipid technology described here has broad applications for the development of distinctive and effective immune responses to other pathogens of importance.
authors.affiliation: Foreign Animal Disease Research Unit, United States Department of Agriculture, Agricultural Research Service, Plum Island Animal Disease Center, Greenport, NY 11944, USA; Department of Pathobiology and Veterinary Science, CANR, University of Connecticut, Storrs, CT 06269, USA.
authors.forename: Devendra K
authors.initials: DK
authors.lastname: Rai
authors.affiliation: Foreign Animal Disease Research Unit, United States Department of Agriculture, Agricultural Research Service, Plum Island Animal Disease Center, Greenport, NY 11944, USA; Department of Pathobiology and Veterinary Science, CANR, University of Connecticut, Storrs, CT 06269, USA.
authors.forename: Fayna Diaz-San
authors.initials: FD
authors.lastname: Segundo
authors.affiliation: Foreign Animal Disease Research Unit, United States Department of Agriculture, Agricultural Research Service, Plum Island Animal Disease Center, Greenport, NY 11944, USA.
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Schafer
authors.affiliation: Department of Homeland Security, S & T, Targeted Advance Development, Virus, Cellular and Molecular Imaging Agriculture, Agricultural Research Service, Plum Island Animal Disease Center, Greenport, NY 11944, USA.
authors.forename: Thomas G
authors.initials: TG
authors.lastname: Burrage
authors.affiliation: Foreign Animal Disease Research Unit, United States Department of Agriculture, Agricultural Research Service, Plum Island Animal Disease Center, Greenport, NY 11944, USA.
authors.forename: Luis L
authors.initials: LL
authors.lastname: Rodriguez
authors.affiliation: Foreign Animal Disease Research Unit, United States Department of Agriculture, Agricultural Research Service, Plum Island Animal Disease Center, Greenport, NY 11944, USA.
authors.forename: Teresa
authors.initials: T
authors.lastname: de Los Santos
authors.affiliation: Physical and Life Sciences Directorate, Lawrence Livermore National Laboratory, Livermore, CA, USA.
authors.forename: Paul D
authors.initials: PD
authors.lastname: Hoeprich
authors.affiliation: Foreign Animal Disease Research Unit, United States Department of Agriculture, Agricultural Research Service, Plum Island Animal Disease Center, Greenport, NY 11944, USA. Electronic address: Elizabeth.Rieder@ars.usda.gov.
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Rieder
mesh_terms: D000276:Adjuvants, Immunologic; D000818:Animals; D057134:Antibodies, Neutralizing / Q000276:immunology; D000914:Antibodies, Viral / Q000276:immunology; D000956:Antigens, Viral / Q000276:immunology; D005536:Foot-and-Mouth Disease / Q000276:immunology* / Q000517:prevention & control*; D029544:Foot-and-Mouth Disease Virus / Q000235:genetics / Q000276:immunology*; D023061:Gene Order; D016679:Genome, Viral; D007477:Ions; D008074:Lipoproteins / Q000276:immunology; D008670:Metals; D008958:Models, Molecular; D009154:Mutation; D053758:Nanoparticles; D011485:Protein Binding; D011487:Protein Conformation; D011993:Recombinant Fusion Proteins / Q000737:chemistry / Q000235:genetics / Q000276:immunology; D014765:Viral Vaccines / Q000235:genetics / Q000276:immunology*
chemical_list: D000276:Adjuvants, Immunologic; D057134:Antibodies, Neutralizing; D000914:Antibodies, Viral; D000956:Antigens, Viral; D007477:Ions; D008074:Lipoproteins; D008670:Metals; D011993:Recombinant Fusion Proteins; D014765:Viral Vaccines
keywords: 6xHis Tag; FMD vaccine; FMDV; Nanolipoprotein adjuvants