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Immunogen preparation of variable peptidic epitopes and preparation method thereof

An immunogen, variable technology, applied in the fields of biochemical equipment and methods, medical preparations containing active ingredients, chemical instruments and methods, etc., can solve problems such as difficulties in the definition and characterization of synthetic routes, and the danger of mixed peptides.

Inactive Publication Date: 2010-07-28
VARIATION BIOTECHNOLOGIES INC
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

If the ability of T cells to recognize foreign antigens is degraded, mixed peptides risk containing peptides that mimic self-antigens, which will induce pathogenic autoimmune responses
Moreover, the complexity of the aforementioned synthetic routes makes it difficult, if not impossible, to define and characterize multiple formulations of the same composition

Method used

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  • Immunogen preparation of variable peptidic epitopes and preparation method thereof
  • Immunogen preparation of variable peptidic epitopes and preparation method thereof
  • Immunogen preparation of variable peptidic epitopes and preparation method thereof

Examples

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preparation example Construction

[0057]The method of the present invention for preparing an immunogen mixture begins with the analysis of the sequence of a naturally occurring pathogen that has been reported in a scientific database or peer-read scientific journal. This work was used to reduce the number of different peptides produced during the synthesis. The amino acids to be added and at which step of the synthesis reaction are determined in advance according to the specific steps, ie after the first calibration of sequences containing known T-helper and B-cell neutralizing epitopes. The resulting mixture of peptides, termed a hypervariable epitope construct (HEC), embodies the variation in the epitope sequence formed during the synthesis of a single peptide by adding a statistically weighted mixture of amino acids to align with the original chain This is achieved by linking the previously assembled amino acids. Thus, unlike mimetic clusters, peptides in HECs are not completely randomly formed, which can ...

Embodiment 1

[0113] Example 1: HIV-1-based HECs

[0114] Epitope protein sequences are provided by the Human Retrovirus and AIDS database (Los Alamos, 1998). Based on the sequence data, five regions of the HIV-1 envelope glycoprotein (gpl20) were identified as hypervariable regions. These five hypervariable regions include antibody neutralizing, CTL, and / or T helper epitopes (HIV Molecular Immunity Database, 1998).

[0115] The probable amino acids at each site on the neutralizing epitope were determined from the sequence composition of in vivo isolates of HIV-1 clade B strains, and the sequence composition of each epitope was calibrated and evaluated. Subsequently, the mixture of suitable amino acids determined from the sequence data obtained above is subjected to an amino acid coupling step for the synthesis of a neutralizing epitope. This step is repeated at each amino acid coupling step in the synthesis. Thus, in one synthesis, a mixture of peptides was prepared representing all mea...

Embodiment 2

[0122] Example 2: HECs based on hepatitis C virus epitopes

[0123] The present invention designs two kinds of HECs against two hypervariable regions of hepatitis C virus (HCV). Sequences of viral in vivo isolates were obtained from databases and peer-read scientific literature, calibrated against these epitopes. According to the principle established by the present invention, when determining the amino acids contained in the variable residue base, the amino acid frequency is rounded to the nearest 25%, and then the proportion of amino acids added in the coupling step is determined. Figure 9 Indicates amino acids occurring at different positions in the peptide mixture. The mixture was synthesized using standard Fmoc chemistry.

[0124] especially, Figure 9 HCV HEC-1 in HEC-1 constitutes a 24-mer with equal amounts of tyrosine (Y) and histidine (H) at residue 4 and an equal amount of leucine (L) at position 17 and phenylalanine (F), with equal amounts of alanine (A) and (...

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Abstract

A process is disclosed for preparation of a immunogenic peptide mixture in a single synthesis. The peptide mixture collectively represents the in vivo variability seen in immunogenic epitopes from a pathogen. The mixture is termed a hypervariable epitope construct (HEC). Immunization with a HEC evokes broadly reactive immunity against divergent strains of a pathogen upon which the HEC is based.

Description

technical field [0001] The invention relates to an immunogen preparation and a preparation method thereof, in particular to a method for preparing an immunogen peptide mixture based on selected amino acids selected from amino acids present at variable residues of protein epitopes. Background technique [0002] Many pathogens, including viruses such as HIV-1 and HIV-2, influenza, hepatitis A / B / C, human papilloma (HPV), and dengue, as well as parasites such as malaria and trichinella, are susceptible to changes especially The sequence of amino acids in a protein epitope. In view of this behavior and other objectives, synthetic peptide vaccines are increasingly being explored as alternatives to attenuated or inactivated vaccines. Epitopes that confer effective immunity are selected, while epitopes that produce harmful immune responses, such as promoting disease formation or suppressing T-cells, should be excluded from the scope of vaccine candidates. In addition, since the sy...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): A61K39/00A61P31/18C07K17/02G01N33/68C07K17/06C07K14/16C07K14/18C07K14/11C12N15/09A61K47/48A61P31/16C07K14/155
CPCC12N2760/16122C12N2740/16122C07K14/005A61K47/4833C12N2770/24222A61K39/00A61K47/646A61P31/16A61P31/18
Inventor 若泽·V·托里斯
Owner VARIATION BIOTECHNOLOGIES INC