Methods to improve immunogenicity of antigens and specificity of antibodies

Abstract

A method of improving specific immune responses to smal immunogens, haptens, has been developed by changing the linkage between the hapten and carrier being used for immunization. High affinity antibodies to the hapten cotinine have been produced using this method. Antibodies to a glycated protein have also been developed, utilizing an immunogen which is composed of a glycated peptide mimic of the glycated peptide sequence which is the target epitope, wherein the peptide mimic is constructed to conformationally mimic the conformation of the peptide in the native protein, the peptide mimic contains no charged groups or other immunodominant group, and the peptide mimic is connected to a spacer sequence equivalent to a peptide spacer of between one and thirty amino acids in length, which serves to position the peptide epitope in a conformation that approximates its conformation in the native protein. In a further embodiment the peptide mimic and spacer are linked to a carrier molecule. This method has been used to produce an antibody to the glycated protein HbAb1c, wherein the peptide mimic includes a valine modified by addition of a glucose molecule, an analog of llistidine which does not bear a charge in the immunizing structure, allows orientation of the peptide so that the immune response can be directed to the side of the peptide chain oriented oppositely to the ring, and is of a size that the conformation of the peptide mimics the conformation of the peptide in the native molecule, a leucine or an analog thereof which allows binding to an antibody preferentially recognizing Hb Alc such as 82D259, and a threonins or an analog thereof which allows binding to antibody number 82D259. In the example described below the histidine analog is 2-amino-3-flurylpropionyl, and the peptide is Fructosyl-Val-2- amino-3-furanylproprionic acid-Leu-Pro-Pro-Glu-Glu-Tyr-Tyr-Cys

Dependencies are inferred from the claim text.