title: Virus-like particles and α-galactosylceramide form a self-adjuvanting composite particle that elicits anti-tumor responses.
abstract: Virus-like particles (VLP) are effective vehicles for delivery of heterologous antigen to antigen-presenting cells. However VLP alone are insufficiently stimulatory to generate the signals required to facilitate effective priming of naïve T cells. We show that the VLP derived from rabbit hemorrhagic disease virus can bind the galactose-containing adjuvant α-galactosylceramide to form a composite particle for co-delivery of antigen and adjuvant to the same antigen-presenting cell. Vaccination with VLP and α-galactosylceramide activated splenic iNKT cells to produce IFN-γ and IL-4, led to the generation of antigen-specific T cells that protected prophylactically against subcutaneous tumor challenge, and was more effective at generating anti-tumor immune responses than either component individually. These data demonstrate a novel method for immunopotentiating VLP to increase their efficacy in the generation of anti-tumor responses via the innate ligand recognition properties of calicivirus-derived nanoparticles.
authors.affiliation: Malaghan Institute of Medical Research, PO Box 7060, Wellington 6242, New Zealand.
authors.forename: Sara J
authors.initials: SJ
authors.lastname: McKee
authors.forename: Vivienne L
authors.initials: VL
authors.lastname: Young
authors.forename: Fiona
authors.initials: F
authors.lastname: Clow
authors.forename: Colin M
authors.initials: CM
authors.lastname: Hayman
authors.forename: Margaret A
authors.initials: MA
authors.lastname: Baird
authors.forename: Ian F
authors.initials: IF
authors.lastname: Hermans
authors.forename: Sarah L
authors.initials: SL
authors.lastname: Young
authors.forename: Vernon K
authors.initials: VK
authors.lastname: Ward
mesh_terms: D000276:Adjuvants, Immunologic / Q000008:administration & dosage / Q000627:therapeutic use; D000818:Animals; D019496:Cancer Vaccines / Q000008:administration & dosage / Q000276:immunology* / Q000627:therapeutic use; D045744:Cell Line, Tumor; D003713:Dendritic Cells / Q000276:immunology; D005699:Galactosylceramides / Q000008:administration & dosage / Q000276:immunology* / Q000627:therapeutic use; D017929:Hemorrhagic Disease Virus, Rabbit / Q000235:genetics / Q000276:immunology*; D008297:Male; D008546:Melanoma, Experimental / Q000276:immunology / Q000628:therapy; D051379:Mice; D008810:Mice, Inbred C57BL; D009368:Neoplasm Transplantation; D013601:T-Lymphocytes / Q000276:immunology; D014771:Virion / Q000235:genetics / Q000276:immunology
chemical_list: D000276:Adjuvants, Immunologic; D019496:Cancer Vaccines; D005699:Galactosylceramides; C493154:alpha-galactosylceramide