Use of carrier peptides for linking B epitope or semiantigen and immunogen containing carrier peptide in medicine and immunology

A peptide immunogen and carrier peptide technology, applied in immunology, pharmacy and medical related fields, can solve the problem of promoting B cell epitope or peptide hapten immunogenicity, to improve immunogenicity, increase CD4+, reduce CD8 +T cell effect

Inactive Publication Date: 2019-06-04
CHINA PHARM UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Immunization of model animals with IA-2 or its B cell epitopes is a strategy for the prevention and treatment of type 1 diabetes, but it is not used as a carrier peptide or a part of the carrier peptide to promote the immunogenicity of B cell epitopes or peptide haptens. to prepare antibodies, especially monoclonal antibodies

Method used

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  • Use of carrier peptides for linking B epitope or semiantigen and immunogen containing carrier peptide in medicine and immunology
  • Use of carrier peptides for linking B epitope or semiantigen and immunogen containing carrier peptide in medicine and immunology
  • Use of carrier peptides for linking B epitope or semiantigen and immunogen containing carrier peptide in medicine and immunology

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0037] Example 1: A class of structured carrier peptides containing T helper epitopes (Th epitopes) IA-2(5)-P2-1,2-IA-2(5)-P2-1,3-IA -2(5)-P2-1, 4-IA-2(5)-P2-1, IA-2(5)-6-P2-1, etc. (abbreviated as IP, 2-IP, 3-IP, 4 -IP, I6P, etc.) preparation.

[0038] A linear B cell epitope IA2(5) peptide segment of IA-2 is selected, the amino acid sequence 1 is shown in SEQ ID NO.1, the Th2 epitope P2 peptide segment at the C-terminal of P277, the amino acid sequence 2 is shown in SEQ ID NO.2, P2 The modified peptide (position 448 or position 455 is any amino acid residue, see SEQ ID NO. 2 for the amino acid sequence). When the 455th position is the amino acid residue A, it is named PA, and when the 448th position is the amino acid residue A, it is named AP.

[0039] Using a variety of analysis software and screening, analysis, identification and modification of multiple STZ diabetic model mouse experiments, it was determined that the two epitopes were linked by flexible peptides, and th...

Embodiment 2

[0040] Example 2: Preparation of B cell epitopes or synthetic peptide hapten B.

[0041]Using a variety of B cell antigen epitope analysis software and online analysis tools, based on a single parameter, combined with secondary structure prediction and spatial structure characteristics, respectively, from a target antigen protein (such as: human DPP4 or human XOD or human uric acid transporter protein). 1 or more than 100 epitopes of human acetylcholinesterase) to select multiple dominant B cell antigen epitopes or peptide hapten B, by combining with carrier peptide IP, 2-IP, 3-IP, 4-IP, 6-IP IP and I6P are linked with flexible peptides, and the B cell epitope or synthetic peptide hapten B with high immunogenicity is obtained through the process of screening, re-engineering and re-screening in immunization animal experiments.

Embodiment 2-1

[0042] Example 2-1 When B is the dominant B cell epitope of human dipeptidyl peptidase 4 (DPP4), the preparation method is to select D41, D42, D43, D44- ---- etc. Multiple predicted dominant B cell epitopes or peptide hapten B, by combining with carrier peptides IP, 2-IP, 3-IP, 4-IP, 6-IP and I6P etc. N-terminal to flexible The peptides are linked to form peptide immunogens, and the highly immunogenic B cell antigen epitopes or peptide haptens D41, D42, D43, etc. are obtained through screening of immunized animals. D41 is a polypeptide sequence 88VFLENSTFDE97 of DPP4, with a total of 10 amino acid residues.

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Abstract

The invention provides structurally similar carrier peptides, which can be linked to a B cell epitope or a peptide semiantigen to constitute peptide immunogen, and simplifies the preparation of an antigen for immunization and has important applications in medicine and immunology. The peptide immunogen containing the carrier peptide of the present invention is used for immunizing different mice, and the immunogenicity of the B cell epitope or the peptide semiantigen is remarkably enhanced, and a Th2 antibody having a high specific binding to the target antigen protein is produced, after immunization with the peptide immunogen, the specific Th2 antibody can be prepared by a hybridoma technology or antibody preparation methods such as antibody libraries and single cells, the immune regulationof Th2 is significantly enhanced, enzyme activity or related protein function can be inhibited, and the condition can be improved. Meanwhile, the carrier peptide and the carrier peptide-containing immunogen provided by the present invention can also be used for recombinant microorganisms and transgenic animals or plants and cells thereof, and can be used as a production plant to prepare vaccinesor to prepare oral vaccines or to prepare the specific antibodies and alterations for the control of Th1 dominant or peptide epitope-related diseases including but not limited to diabetes and complications, and for the development of detection reagents.

Description

technical field [0001] The present invention relates to the fields of immunology, pharmacy and medicine. The present invention relates to carrier peptides with a class of similar structures, immunogens containing such carrier peptides, and applications thereof, in particular, such carrier peptides are used to target antigens with B cell epitopes or peptide haptens, that is, a target antigenic protein The site is covalently linked into a peptide immunogen, which can enhance the immunogenicity of the target antigenic site (B cell epitope or peptide hapten) and can be used for the preparation of prophylactic and therapeutic vaccines and specific and B cell epitopes containing or or Various types of antibodies (which can be polyclonal antibodies, monoclonal antibodies, and various types of antibodies based on antibody preparation techniques such as antibody libraries and single cells after immunization with such peptide immunogens) bind to the target antigen protein of peptide imm...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07K19/00C07K16/00A61K39/00A61K39/395A61P3/10A61P19/06A61P13/12A61P3/06A61P9/10A61P19/02A61P29/00A61P25/28A61P27/02A61P9/00
Inventor 李泰明顾小骞焦瑞马艳洁方金芝程鹏
Owner CHINA PHARM UNIV
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