title: An IL-17 peptide-based and virus-like particle vaccine enhances the bioactivity of IL-17 in vitro and in vivo.
abstract: OBJECTIVE
  To develop an IL-17 peptide-based virus-like particle vaccine that elicits autoantibodies to IL-17 and to evaluate the effects of the vaccine in mice with experimental colitis.
  
  
  METHODS
  Recombinant IL-17 vaccines were constructed by inserting selected peptides derived from mouse IL-17 into the carrier protein, hepatitis B core antigen, using molecular engineering methods. To evaluate the in vivo effects of the vaccine, mice with 2,4,6-trinitrobenzene sulfonic acid-induced chronic colitis were injected three times with the vaccine, carrier or saline after the second delivery of 2,4,6-trinitrobenzene sulfonic acid. Colon inflammation and fibrosis were evaluated by histological examination. Serum IL-17-specific IgG and colon-tissue cytokine levels were measured by ELISA. In vitro inhibition tests of sera from vaccine-immunized mice were performed using IL-17-induced IL-6 production by NIH 3T3 cells and IL-17-induced TNF production by macrophages.
  
  
  RESULTS
  Immunization with the vaccine without the use of adjuvants induced high-titered and long-lasting antibodies to IL-17. Unexpectedly, vaccinated mice exhibited increases in colon inflammation, collagen deposition, levels of TNF and IL-17 cytokines compared with carrier and saline groups. Furthermore, in vitro study revealed that serum IL-17-specific IgG from vaccine-immunized mice significantly enhanced IL-17-induced IL-6 production and IL-17-induced TNF production dose-dependently.
  
  
  CONCLUSIONS
  The IL-17 peptide-based vaccine enhances the bioactivity of IL-17 in vitro and in vivo, providing a potential immunotherapy for treatment of diseases associated with insufficient IL-17 production, such as hyper-IgE syndrome.
authors.affiliation: Department of Immunology, University of Manitoba, Winnipeg, Manitoba, Canada.
authors.forename: Qingdong
authors.initials: Q
authors.lastname: Guan
authors.forename: Carolyn R
authors.initials: CR
authors.lastname: Weiss
authors.forename: Gefei
authors.initials: G
authors.lastname: Qing
authors.forename: Yanbing
authors.initials: Y
authors.lastname: Ma
authors.forename: Zhikang
authors.initials: Z
authors.lastname: Peng
mesh_terms: D000818:Animals; D003092:Colitis / Q000139:chemically induced / Q000276:immunology* / Q000628:therapy*; D003106:Colon / Q000276:immunology; D005260:Female; D006512:Hepatitis B Core Antigens / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D006801:Humans; D007074:Immunoglobulin G / Q000097:blood; D007167:Immunotherapy / Q000379:methods*; D020381:Interleukin-17 / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D015850:Interleukin-6 / Q000378:metabolism; D008264:Macrophages / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D023421:Models, Animal; D041681:NIH 3T3 Cells; D010446:Peptide Fragments / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D015202:Protein Engineering; D014302:Trinitrobenzenesulfonic Acid / Q000008:administration & dosage; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D058425:Vaccines, Virus-Like Particle / Q000276:immunology*
chemical_list: D006512:Hepatitis B Core Antigens; D007074:Immunoglobulin G; D020381:Interleukin-17; D015850:Interleukin-6; D010446:Peptide Fragments; D014409:Tumor Necrosis Factor-alpha; D058425:Vaccines, Virus-Like Particle; D014302:Trinitrobenzenesulfonic Acid