Synthetic IgE peptide vaccine for immunotherapy of allergy.
An immunotherapeutic vaccine for allergy was produced by designing IgE-based synthetic peptide immunogens and selecting them for functional immunogenicity. The vaccine targets the binding site on IgE for the high affinity receptor Fc epsilon RI, by active immunization. The peptide target site on IgE heavy chain was selected from among the amino acid sequences for the C epsilon 2, C epsilon 3, and C epsilon 4 domains. These were characterised by epitope mapping studies for cross-reactivity to IgE and functional antigenicity. A peptide, modified from positions 413-435 of a loop region of C epsilon 3 and subjected to conformational constraint, elicited anti-IgE antibodies that blocked IgE-mediated histamine release. It was immunopotentiated by linkage to a promiscuous T helper site to produce a wholly synthetic chimaeric immunogen. This immunogen was shown to induce polyclonal site-specific anti-IgE antibodies that obstruct binding to Fc epsilon RI, inhibit histamine release by IgE-sensitised basophils, inhibit passive cutaneous anaphylaxis, and do not signal degranulation. Immunized dogs experienced significant reductions in total serum IgE.
Wang
Chang Yi
CY
United Biomedical Inc., 25 Davids Drive, Hauppauge, NY 11788, USA. cywang@unitedmedical.com
Walfield
Alan M
AM
Fang
Xinde
X
Hammerberg
Bruce
B
Ye
John
J
Li
Ming Lie
ML
Shen
Fan
F
Shen
Ming
M
Alexander
Valerie
V
MacGlashan
Donald W
DW
D000595:Amino Acid Sequence; D000818:Animals; D001666:Binding Sites, Antibody; D003888:Desensitization, Immunologic / Q000379:methods*; D004285:Dogs; D016503:Drug Delivery Systems / Q000379:methods; D006168:Guinea Pigs; D006801:Humans; D006967:Hypersensitivity / Q000276:immunology / Q000517:prevention & control*; D007073:Immunoglobulin E / Q000276:immunology / Q000378:metabolism / Q000627:therapeutic use*; D051379:Mice; D008807:Mice, Inbred BALB C; D008969:Molecular Sequence Data; D017455:Receptors, IgE / Q000378:metabolism; D013552:Swine; D022223:Vaccines, Subunit / Q000627:therapeutic use; D014614:Vaccines, Synthetic / Q000627:therapeutic use
D017455:Receptors, IgE; D022223:Vaccines, Subunit; D014614:Vaccines, Synthetic; D007073:Immunoglobulin E