title: Virus-derived tubular structure displaying foreign sequences on the surface elicit CD4+ Th cell and protective humoral responses.
abstract: Particulate vector systems for the presentation of immunogenic epitopes provide an alternate and powerful approach for the delivery of immunogens of interest. In this article, we have exploited a viral protein of unknown function, bluetongue virus (BTV) nonstructural protein NS1, which forms distinct tubular aggregates in infected cells, as an immunogen delivery system. Tubules are helical assemblies of NS1 protein that present the C-terminus of the protein to the outer edge effectively displaying appended residues in a regular and repeating array akin to the coat of a filamentous phage. To assess the breadth of response induced following tubule-based immunization, two different immunodominant foreign peptides were inserted at the C-terminus of NS1 and chimeric tubules generated following expression in the baculovirus expression system. Both constructs, one carrying a peptide of foot and mouth disease virus (FMDV) (aa 135-144 of VP1) and the other, a peptide of influenza A virus (aa 186-205 of HA), effectively assembled into tubules and were easily purified. Subsequently, using in vitro assay systems, we demonstrated that each purified chimeric particle was capable of eliciting strong immune responses. Further, NS1-FMDV chimeric tubules could induce a potent immune response that could protect against disease.
authors.affiliation: Department of Medicine, University of Alabama at Birmingham, 35294, USA.
authors.forename: M K
authors.initials: MK
authors.lastname: Ghosh
authors.forename: M V
authors.initials: MV
authors.lastname: Borca
authors.forename: Polly
authors.initials: P
authors.lastname: Roy
mesh_terms: D000818:Animals; D016367:Baculoviridae; D001820:Bluetongue virus / Q000276:immunology* / Q000648:ultrastructure; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D036022:Capsid Proteins / Q000737:chemistry / Q000276:immunology; D019267:Hemagglutinin Glycoproteins, Influenza Virus / Q000737:chemistry / Q000276:immunology; D007114:Immunization; D008213:Lymphocyte Activation; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D011993:Recombinant Fusion Proteins / Q000276:immunology*; D011995:Recombination, Genetic; D018411:Spodoptera; D017361:Viral Nonstructural Proteins / Q000235:genetics / Q000276:immunology* / Q000648:ultrastructure*; D014765:Viral Vaccines / Q000276:immunology
chemical_list: D036022:Capsid Proteins; D019267:Hemagglutinin Glycoproteins, Influenza Virus; C078966:NS1 protein, bluetongue virus; D011993:Recombinant Fusion Proteins; C442501:VP1 protein, Foot-and-mouth disease virus; D017361:Viral Nonstructural Proteins; D014765:Viral Vaccines