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Epitope peptide capable of inducing broad-spectrum protective antibody by H1N1 influenza virus hemagglutinin and application

A technology of influenza and virus, applied in the field of immunology and biomedicine, can solve the problem that the preventive efficacy is difficult to reach the human standard

Active Publication Date: 2019-07-12
SHANGHAI INST OF PLANNED PARENTHOOD RES
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, due to the limitation of non-conformational antibody epitope identification methodology in the past, only one or a few epitopes in the target protein antigen can be known (seeing the difficulty and difficulty of finding a new antigenic epitope on the target protein). Synthetic peptide vaccines, so its preventive efficacy is difficult to meet human standards, so that no chemically synthesized peptide vaccine has been approved by the US FDA for more than 50 years

Method used

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  • Epitope peptide capable of inducing broad-spectrum protective antibody by H1N1 influenza virus hemagglutinin and application
  • Epitope peptide capable of inducing broad-spectrum protective antibody by H1N1 influenza virus hemagglutinin and application
  • Epitope peptide capable of inducing broad-spectrum protective antibody by H1N1 influenza virus hemagglutinin and application

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0091] Example 1. Identification of refined epitopes covering HA0 cleavage sites using rabbit anti-A / H1N1-HA polyclonal antibodies

[0092] IAV-HA0 is blocked by host cells such as trypsin, bromelain, thermolysin, elastase, plasmin, and chymotrypsin Cleavage by specific proteases into HA1 and HA2 subunits is a key event that determines the infectivity of IAV subtypes in the host. After in-depth research, the inventors speculated that there may be a non-conformational antibody epitope involved in HAO cleavage in the overlapping region of the blot-positive P36 and P37 peptides. Then, in order to confirm this inference that may have significant discovery significance, the inventors constructed and expressed a group of 16 SP short peptides (fusion proteins) that covered the full-length sequences of P36 and P37 and overlapped each other by 7 residues. After SDS-PAGE electrophoresis and transfer to nitrocellulose membranes, rabbit anti-A / H1N1-HA antiserum was used for blot identifi...

Embodiment 2

[0100] Example 2, Broad-spectrum Analysis of A / H1N1-HA Epitope Peptides in IAV / IBV Homologous Proteins

[0101] After identifying the epitope of the IAV target protein antigen, the inventors further studied its specificity and conservation characteristics in homologous proteins. The former characteristic can be used to prepare the specific detection antigen of IAV subtype / mutant strain, and the latter characteristic Then it can be used as an immunogen (epitope) for developing monovalent / multivalent broad-spectrum recombinant peptide influenza vaccine.

[0102] Therefore, in order to demonstrate more and more valuable uses of the epitope peptides of the present invention, the inventors based on the advantages of the obtained fine epitope motifs and the HA information of 18 IAV-H subtypes / mutant strains in the GenBank database, carried out Alignment of homologous protein sequences based on fine epitope motifs has achieved clearer and more reliable results that were difficult to ...

Embodiment 3

[0105] Example 3, Identification of cross-reactivity between A / H1N1-HA antiserum and IAV-HA cleavage site mutant peptide

[0106] Although it is known that the HA cleavage sites R↓G and HA2-FP are highly conserved among IAV subtypes, by searching and comparing a large number of IAV subtypes / mutant HA homologous HA protein sequences, the table of the present invention can be found There are three residue mutation sites in the peptide. Here, the first residue at the N-terminus of the epitope peptide of the present invention is determined as site +1, and the following analogy is respectively expressed as +3 and +4. Among the three mutation points suggested in Table 1, most of the +3 "L" residues were mutated into "I" residues, and several IAV subtypes were involved. For example: A / Dunedin / 73 (AF201842), A / Moscow / 2003 (AAZ32953), A / Brisbane / 2007 (ABW23353) and A / Kenya / 2017 (ASV62056) of H3N2 mutants, and H6N1 subspecies Type A / chicken / Taiwan / 05 (ABD35556) and H9N1 strain A / laugh...

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Abstract

The invention provides an epitope peptide capable of inducing a broad-spectrum protective antibody by H1N1 influenza virus hemagglutinin. The epitope peptide is from an influenza A virus (IAV) H1N1 hemagglutinin (HA) cleavage site. Besides the H14 subtype, the epitope peptide almost 100% conservatively exists in 17 IAV-H subtype HA proteins of partial H8. The epitope peptide can be used for preparing anti-influenza broad-spectrum therapeutic antibody medicines and detection antigens, or used for preparing univalent / multivalent preventive influenza vaccines for human and / or poultry.

Description

technical field [0001] The invention belongs to the technical field of immunology and biomedicine, more specifically, the invention relates to an epitope peptide of an influenza A virus (IAV) hemagglutinin (HA) protein that can induce antibodies that block HA precursor (HA0) cleavage and its application. Background technique [0002] Influenza virus is a RHA virus belonging to the family Orthomyxoviridae, and there are four genera of A (A), B (B), C (C) and D (D) [Hause BM, et al.Characterization of a novel influenza virus in cattle and swine: proposal for a new genus in the Orthomyxoviridae family. MBo 2014, 5:e00014-e00031], wherein the influenza A virus (IAV) with a wide host range and multiple serotypes, according to its The antigenic differences caused by antigenic shift and antigenic drift of hemagglutinin (HA) and neuraminidase (NA) exposed on the surface of the virus are further subdivided into different subtypes. There are 18 HA subtypes (H1~H18) and 11 NA subtype...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07K14/11C12N15/44C12N7/00A61K39/145A61P31/16
CPCC07K14/005C12N7/00A61K39/12A61P31/16C12N2760/16122C12N2760/16121C12N2760/16162C12N2760/16134C07K2319/00
Inventor 李元春谢毅王健戴建锋唐海平顾少华季朝能程一航连文博詹建民徐万祥
Owner SHANGHAI INST OF PLANNED PARENTHOOD RES
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