title: Novel IgE peptide-based vaccine prevents the increase of IgE and down-regulates elevated IgE in rodents.
abstract: BACKGROUND
  Immunotherapy with anti-IgE antibodies for treatment of allergy is promising but a short half-life and extremely high cost limit its application.
  
  
  OBJECTIVE
  We sought to develop IgE vaccines that induce longer-lasting auto-antibodies to neutralize self-IgE as an alternative therapy.
  
  
  METHODS
  The vaccine was made by conjugating three synthetic peptides corresponding to human IgE receptor-binding sites to a carrier, hepatitis B surface antigen. To test the immunogenicity of the vaccine, rats were immunized with the vaccine or hepatitis B surface antigen as control. Serum IgG titres to human IgE and the IgE of other species were measured. The inhibition by rat antisera of the binding of human IgE to its receptor was assessed by ELISA, flow cytometry analysis, and passive cutaneous anaphylaxis (PCA), and its ability to recognize receptor-bound IgE was examined. The in vivo effect of the vaccine was evaluated in trichosanthin-sensitized mice and rats. In the preventative study, vaccination started before sensitization commenced, while in the treatment study, vaccination started after sensitization. Sensitized mice and rats receiving injections of the carrier served as controls. Trichosanthin-specific IgE was measured using PCA.
  
  
  RESULTS
  Sera from vaccine-immunized rats contained high titre antibodies that reacted with soluble and plate-bound but not with receptor-bound human IgE; they also reacted with mouse, rat, and dog IgE. Furthermore, the sera inhibited the binding of human IgE to its receptor in a dose-dependent manner. In preventative and treatment studies, serum trichosanthin-specific IgE levels were significantly reduced in vaccinated groups compared with controls.
  
  
  CONCLUSIONS
  Antibodies against self-IgE can be induced by IgE peptide-based vaccines, which are effective in preventing the increase of IgE and in down-regulating IgE in sensitized animals.
authors.affiliation: Department of Pediatrics and Child Health, University of Manitoba, Winnipeg, Manitoba, Canada. zpeng@ms.umanitoba.ca
authors.forename: Z
authors.initials: Z
authors.lastname: Peng
authors.forename: Q
authors.initials: Q
authors.lastname: Liu
authors.forename: Q
authors.initials: Q
authors.lastname: Wang
authors.forename: E
authors.initials: E
authors.lastname: Rector
authors.forename: Y
authors.initials: Y
authors.lastname: Ma
authors.forename: R
authors.initials: R
authors.lastname: Warrington
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000097:blood*; D000918:Antibody Specificity; D001323:Autoantibodies / Q000097:blood*; D003429:Cross Reactions; D004285:Dogs; D004306:Dose-Response Relationship, Immunologic; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005434:Flow Cytometry; D006514:Hepatitis B Surface Antigens / Q000276:immunology; D006801:Humans; D006967:Hypersensitivity / Q000276:immunology / Q000378:metabolism / Q000517:prevention & control*; D007114:Immunization; D007073:Immunoglobulin E / Q000276:immunology* / Q000378:metabolism; D007074:Immunoglobulin G / Q000097:blood; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D010323:Passive Cutaneous Anaphylaxis / Q000276:immunology; D051381:Rats; D017208:Rats, Wistar; D017455:Receptors, IgE / Q000378:metabolism; D015978:Trichosanthin / Q000276:immunology; D022223:Vaccines, Subunit / Q000276:immunology*
chemical_list: D000911:Antibodies, Monoclonal; D001323:Autoantibodies; D006514:Hepatitis B Surface Antigens; D007074:Immunoglobulin G; D017455:Receptors, IgE; D022223:Vaccines, Subunit; D007073:Immunoglobulin E; D015978:Trichosanthin