CN-117659140-B - Novel coronavirus HLA-A2 restriction epitope peptide and application thereof

Abstract

Provided herein are novel coronavirus HLa-a2 restriction epitope peptides and uses thereof. In particular, provided herein is an isolated polypeptide having the amino acid sequence FLWLLWPVT (SEQ ID NO: 5) which is a novel coronavirus SARS-CoV-2HLa-a2 restriction epitope polypeptide. Also provided herein are complexes, articles of manufacture, and uses thereof comprising the polypeptides. The related active substances and products of the application can be used for detecting, diagnosing, preventing and/or treating SARS-CoV-2 related diseases.

Inventors

• YU GANJUN
• WU YANFENG
• HE XIAOBO
• LI NAN
• XU RONGRONG
• XU JIA

Assignees

• 中国人民解放军海军军医大学

Dates

Publication Date

20260505

Application Date

20231026

Claims (6)

1. 1. A complex comprising a polypeptide having the amino acid sequence FLWLLWPVT (SEQ ID NO: 5), wherein the complex is an antigen presenting cell loaded with the polypeptide, wherein the antigen presenting cell is a dendritic cell.
2. 2. An article comprising the composite of claim 1.
3. 3. The article of manufacture of claim 2, wherein the article of manufacture is a kit.
4. 4. Use of a complex according to claim 1 or an article according to any one of claims 2 to 3 for the preparation of a product which is a specific immune effector cell specific for a polypeptide having an amino acid sequence FLWLLWPVT (SEQ ID NO: 5), wherein the product is used for the detection, diagnosis, prevention and/or treatment of SARS-CoV-2.
5. 5. A method of preparing a product that is a specific immune effector cell specific for a polypeptide having the amino acid sequence FLWLLWPVT (SEQ ID NO: 5), the method comprising: (a) Providing a composite according to claim 1 or an article according to any one of claims 2 to 3; (b) The complex or preparation of (a) is used for stimulation of the immune effector cells, wherein the product is used for detection, diagnosis, prevention and/or treatment of SARS-CoV-2.
6. 6. A specific immune effector cell produced by the method of claim 5 for use in detection, diagnosis, prevention and/or treatment of SARS-CoV-2.

Description

Novel coronavirus HLA-A2 restriction epitope peptide and application thereof Technical Field The present application relates to the field of immunology and biomedical. More particularly, the present application relates to SARS-CoV-2 virus HLA-A2 restriction epitope polypeptide (e.g., polypeptide of SEQ ID NO: 5), as well as to said epitope polypeptide and complexes, products and uses thereof, e.g., in the manufacture of products for the detection, diagnosis, prevention and/or treatment of SARS-CoV-2 related disease. Background The main clinical symptoms of the new coronary patients infected with SARS-CoV-2 are fever, cough, shortness of breath and the like, and the laboratory examination frequently shows multiple transmission glass shadows of the lung. Part of the patient's condition may rapidly deteriorate and serious complications occur, including acute respiratory distress syndrome, acute kidney injury, secondary infections, inflammatory factor storms, etc., and part of the patient eventually dies from respiratory failure, multiple organ dysfunction or shock. The pathogen SARS-CoV-2 causing disease is identified by laboratory as a newly discovered beta-genus coronavirus, which has 79% genetic similarity with the pathogen SARS-CoV of the epidemic situation of 2003, the diameter is 60-140 nm, and the virus has envelope, single-chain and sense RNA genome. The SARS-CoV-2 genome is flanked by 5 'and 3' untranslated regions, the 5 'end comprising 2 longer Open Reading Frames (ORFs) encoding 16 nonstructural proteins, and the remaining genome near the 3' end encodes primarily structural and other accessory proteins. The structural proteins of the virus mainly include spike protein (S protein), membrane glycoprotein (M protein), small envelope protein (envelope glycoprotein, E protein), nucleocapsid protein (nucleocapsid protein, N protein). The S protein can bind host cells and mediate virus infection, is the main antigen protein for the research and development reference of the antibody and vaccine at present, but under the long-term persistence of epidemic situation, SARS-CoV-2 continuously accumulates mutation, especially mutation of structural protein, in the host, so that a plurality of SARS-CoV-2 mutant strains with adaptability advantages, such as armstrong, etc., are produced. These mutants generally have a stronger infectious or pathogenic potential and mutations may lead to alterations in antigenic properties, thereby affecting the control of prophylactic vaccines and therapeutic antibodies against the mutants, resulting in immune escape of the virus in the body. Based on genetic sequence analysis, structural protein mutations are mainly concentrated on the S protein and the N protein, which presents a great challenge to vaccines or antibodies developed based on S protein antigen information. M protein is essentially a kind of transmembrane protein, and is structurally characterized by having three structural domains, namely an N-terminal extracellular domain, a three-transmembrane domain and an internal C-terminal domain, and plays an important role in the morphogenesis and maintenance of viruses, and is the most abundant glycoprotein in virus particles. More critical is that the M gene is relatively conserved, the frequency of mutation of the M protein is far lower than that of the S protein, and vaccines or antibodies developed based on the M protein are not easy to cause reduction of prevention and treatment effects due to virus mutation. Therefore, if the M protein is used as a target for immunization of an organism, on one hand, the organism can generate specific immune response aiming at the virus M protein, so that the organism can effectively remove viruses, measures are provided for preventing and treating SARS-CoV-2, and on the other hand, the relatively conservative low mutation characteristic can further avoid immune escape of the viruses caused by mutation, and the immune escape has a broader-spectrum effect. The synthetic peptide vaccine is a new vaccine developed along with the development of molecular biology and immunology in recent years, can induce organisms to generate specific immune response, has slight side effect and good safety, is a popular direction of current vaccine research, and is widely applied to anti-tumor and antiviral immunotherapy. A variety of epitope polypeptide-based vaccines are currently in clinical research or market. HLA-A 0201 is an MHC class I molecule with higher distribution in people in China, the positive rate is 40-60%, and the HLA-A 0201 is the first molecule of each subgroup of MHC class I molecules and is the first choice related molecule in vaccine design. At present, a plurality of HLA-A x 0201 restrictive CTL epitopes have been identified, and some have shown better curative effect in clinic. However, due to the diversity and complexity of cellular epitopes, intensive research into specific proteins is still required to develop epitope polypept