title: Type VI secretion system sheaths as nanoparticles for antigen display.
abstract: The bacterial type 6 secretion system (T6SS) is a dynamic apparatus that translocates proteins between cells by a mechanism analogous to phage tail contraction. T6SS sheaths are cytoplasmic tubular structures composed of stable VipA-VipB (named for ClpV-interacting protein A and B) heterodimers. Here, the structure of the VipA/B sheath was exploited to generate immunogenic multivalent particles for vaccine delivery. Sheaths composed of VipB and VipA fused to an antigen of interest were purified from Vibrio cholerae or Escherichia coli and used for immunization. Sheaths displaying heterologous antigens generated better immune responses against the antigen and different IgG subclasses compared with soluble antigen alone. Moreover, antigen-specific antibodies raised against sheaths presenting Neisseria meningitidis factor H binding protein (fHbp) antigen were functional in a serum bactericidal assay. Our results demonstrate that multivalent nanoparticles based on the T6SS sheath represent a versatile scaffold for vaccine applications.
authors.affiliation: Department of Microbiology and Immunobiology, Harvard Medical School, Boston, MA 02115.
authors.forename: Elena
authors.initials: E
authors.lastname: Del Tordello
authors.affiliation: Department of Microbiology and Immunobiology, Harvard Medical School, Boston, MA 02115.
authors.forename: Olga
authors.initials: O
authors.lastname: Danilchanka
authors.affiliation: Department of Microbiology and Immunobiology, Harvard Medical School, Boston, MA 02115.
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: McCluskey
authors.affiliation: Department of Microbiology and Immunobiology, Harvard Medical School, Boston, MA 02115 john_mekalanos@hms.harvard.edu.
authors.forename: John J
authors.initials: JJ
authors.lastname: Mekalanos
mesh_terms: D000150:Acinetobacter / Q000737:chemistry / Q000235:genetics; D019881:Aminoacyltransferases / Q000378:metabolism; D000818:Animals; D000907:Antibodies, Bacterial / Q000096:biosynthesis / Q000276:immunology; D000941:Antigens / Q000008:administration & dosage* / Q000276:immunology; D000942:Antigens, Bacterial / Q000008:administration & dosage / Q000276:immunology; D001426:Bacterial Proteins / Q000008:administration & dosage / Q000737:chemistry / Q000276:immunology / Q000378:metabolism; D001428:Bacterial Vaccines / Q000008:administration & dosage / Q000276:immunology; D002460:Cell Line; D003546:Cysteine Endopeptidases / Q000378:metabolism; D019281:Dimerization; D016503:Drug Delivery Systems; D004926:Escherichia coli / Q000737:chemistry; D005260:Female; D017930:Genes, Reporter; D007074:Immunoglobulin G / Q000096:biosynthesis / Q000235:genetics; D008264:Macrophages / Q000502:physiology; D051379:Mice; D008807:Mice, Inbred BALB C; D008854:Microscopy, Electron; D053758:Nanoparticles / Q000008:administration & dosage / Q000737:chemistry* / Q000648:ultrastructure; D011550:Pseudomonas aeruginosa / Q000737:chemistry / Q000235:genetics; D011993:Recombinant Fusion Proteins / Q000008:administration & dosage / Q000276:immunology; D000069376:Type VI Secretion Systems / Q000737:chemistry / Q000648:ultrastructure*; D014611:Vaccination; D014612:Vaccines / Q000008:administration & dosage* / Q000276:immunology; D014734:Vibrio cholerae / Q000737:chemistry
chemical_list: D000907:Antibodies, Bacterial; D000941:Antigens; D000942:Antigens, Bacterial; D001426:Bacterial Proteins; D001428:Bacterial Vaccines; D007074:Immunoglobulin G; D011993:Recombinant Fusion Proteins; D000069376:Type VI Secretion Systems; D014612:Vaccines; C484699:factor H-binding protein, Neisseria meningitidis; D019881:Aminoacyltransferases; C120542:sortase A; D003546:Cysteine Endopeptidases
keywords: antigen; immunogen; nanoparticles; type 6 secretion system; vaccine delivery