title: A self-adjuvanting vaccine induces cytotoxic T lymphocytes that suppress allergy.
abstract: Epitope-based peptide vaccines encompass minimal immunogenic regions of protein antigens to allow stimulation of precisely targeted adaptive immune responses. However, because efficacy is largely determined by the functional status of antigen-presenting cells (APCs) that acquire and present peptides to cells of the adaptive immune system, adjuvant compounds are needed to enhance immunogenicity. We present here a vaccine consisting of an allergen-derived peptide conjugated to a prodrug of the natural killer-like T (NKT) cell agonist α-galactosylceramide, which is highly effective in reducing inflammation in a mouse model of allergic airway inflammation. Unlike other peptide-adjuvant conjugates that directly activate APCs through pattern recognition pathways, this vaccine encourages third-party interactions with NKT cells to enhance APC function. Therapeutic efficacy was correlated with marked increases in the number and functional activity of allergen-specific cytotoxic T lymphocytes (CTLs), leading to suppression of immune infiltration into the lungs after allergen challenge in sensitized hosts.
authors.affiliation: The Ferrier Research Institute, Victoria University of Wellington, Wellington, New Zealand.
authors.forename: Regan J
authors.identifier: 0000000334679202
authors.initials: RJ
authors.lastname: Anderson
authors.affiliation: Malaghan Institute of Medical Research, Wellington, New Zealand.
authors.forename: Ching-wen
authors.initials: CW
authors.lastname: Tang
authors.affiliation: 1] Malaghan Institute of Medical Research, Wellington, New Zealand. [2] Department of Pathology and Molecular Medicine, Wellington School of Medicine and Health Sciences, Wellington, New Zealand.
authors.forename: Naomi J
authors.initials: NJ
authors.lastname: Daniels
authors.affiliation: The Ferrier Research Institute, Victoria University of Wellington, Wellington, New Zealand.
authors.forename: Benjamin J
authors.initials: BJ
authors.lastname: Compton
authors.affiliation: The Ferrier Research Institute, Victoria University of Wellington, Wellington, New Zealand.
authors.forename: Colin M
authors.initials: CM
authors.lastname: Hayman
authors.affiliation: The Ferrier Research Institute, Victoria University of Wellington, Wellington, New Zealand.
authors.forename: Karen A
authors.identifier: 0000000151521410
authors.initials: KA
authors.lastname: Johnston
authors.affiliation: Malaghan Institute of Medical Research, Wellington, New Zealand.
authors.forename: Deborah A
authors.initials: DA
authors.lastname: Knight
authors.affiliation: Malaghan Institute of Medical Research, Wellington, New Zealand.
authors.forename: Olivier
authors.initials: O
authors.lastname: Gasser
authors.affiliation: Malaghan Institute of Medical Research, Wellington, New Zealand.
authors.forename: Hazel C
authors.initials: HC
authors.lastname: Poyntz
authors.affiliation: Capital and Coast District Health Board, Wellington, New Zealand.
authors.forename: Peter M
authors.initials: PM
authors.lastname: Ferguson
authors.affiliation: Department of Chemistry, University of Otago, Dunedin, New Zealand.
authors.forename: David S
authors.initials: DS
authors.lastname: Larsen
authors.affiliation: Malaghan Institute of Medical Research, Wellington, New Zealand.
authors.forename: Franca
authors.initials: F
authors.lastname: Ronchese
authors.affiliation: The Ferrier Research Institute, Victoria University of Wellington, Wellington, New Zealand.
authors.forename: Gavin F
authors.initials: GF
authors.lastname: Painter
authors.affiliation: 1] Malaghan Institute of Medical Research, Wellington, New Zealand. [2] School of Biological Sciences, Victoria University of Wellington, Wellington, New Zealand.
authors.forename: Ian F
authors.initials: IF
authors.lastname: Hermans
mesh_terms: D000276:Adjuvants, Immunologic; D000485:Allergens / Q000008:administration & dosage / Q000737:chemistry / Q000276:immunology; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000378:metabolism / Q000494:pharmacology / Q000627:therapeutic use; D000938:Antigen-Presenting Cells / Q000187:drug effects / Q000276:immunology; D004195:Disease Models, Animal; D005260:Female; D005699:Galactosylceramides / Q000378:metabolism / Q000494:pharmacology / Q000627:therapeutic use; D006967:Hypersensitivity / Q000188:drug therapy / Q000276:immunology*; D007073:Immunoglobulin E / Q000097:blood; D007249:Inflammation / Q000188:drug therapy; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008968:Molecular Conformation; D055611:Natural Killer T-Cells / Q000166:cytology / Q000187:drug effects / Q000276:immunology; D010455:Peptides / Q000008:administration & dosage / Q000737:chemistry / Q000276:immunology; D011355:Prodrugs / Q000737:chemistry* / Q000378:metabolism; D013602:T-Lymphocytes, Cytotoxic / Q000187:drug effects / Q000276:immunology*; D014612:Vaccines / Q000008:administration & dosage / Q000138:chemical synthesis / Q000737:chemistry / Q000276:immunology*
chemical_list: D000276:Adjuvants, Immunologic; D000485:Allergens; D000893:Anti-Inflammatory Agents; D005699:Galactosylceramides; D010455:Peptides; D011355:Prodrugs; D014612:Vaccines; C493154:alpha-galactosylceramide; D007073:Immunoglobulin E