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CN-120590522-B - Neutralizing antibody WN-XH3 for resisting West Nile virus and application thereof

CN120590522BCN 120590522 BCN120590522 BCN 120590522BCN-120590522-B

Abstract

The invention discloses a neutralizing antibody WN-XH3 for resisting west nile virus and application thereof. The antibody contains a heavy chain variable region and a light chain variable region, has better binding activity with West Nile virus E protein and stronger virus neutralization activity, lays a foundation for diagnosis and treatment of diseases related to West Nile virus infection, development of medicines for treating diseases related to West Nile virus infection and the like, can be used as candidates of clinical anti-West Nile virus medicines, and has good application prospects.

Inventors

  • XIAO HE
  • LIU CHENGHUA
  • FENG JIANNAN
  • SHEN BEIFEN
  • ZHU WANLU
  • WANG JING
  • CHEN GUOJIANG
  • QIAO CHUNXIA
  • YU JIJUN
  • LI XINYING

Assignees

  • 中国人民解放军军事科学院军事医学研究院

Dates

Publication Date
20260508
Application Date
20250613

Claims (13)

  1. 1. An antibody or antigen-binding fragment thereof against west nile virus, wherein the antibody comprises a heavy chain variable region comprising HCDR1, HCDR2 and HCDR3, wherein the amino acid sequences of HCDR1, HCDR2 and HCDR3 are respectively shown in SEQ ID No. 5, SEQ ID No. 6 and SEQ ID No. 7, and a light chain variable region comprising LCDR1, LCDR2 and LCDR3, wherein the amino acid sequences of LCDR1, LCDR2 and LCDR3 are respectively shown in SEQ ID No. 8, SEQ ID No. 9 and SEQ ID No. 10.
  2. 2. The antibody or antigen-binding fragment thereof of claim 1, wherein the heavy chain variable region has the amino acid sequence set forth in SEQ ID No. 1; the amino acid sequence of the light chain variable region is shown as SEQ ID NO. 3.
  3. 3. A biomaterial, characterized in that the biomaterial comprises: 1) A polynucleotide encoding the antibody or antigen-binding fragment thereof of any one of claims 1-2; 2) A vector comprising 1) the polynucleotide; 3) A host cell comprising the polynucleotide of 1) or the vector of 2).
  4. 4. The biomaterial according to claim 3, wherein the polynucleotide sequence encoding the heavy chain variable region of the antibody or antigen-binding fragment thereof according to any one of claims 1-2 is shown in SEQ ID No. 2, and the polynucleotide sequence encoding the light chain variable region of the antibody or antigen-binding fragment thereof according to any one of claims 1-2 is shown in SEQ ID No. 4.
  5. 5. A biomaterial according to claim 3 wherein the vector comprises a plasmid, viral vector.
  6. 6. The biomaterial of claim 5, wherein the viral vector comprises a lentiviral, adenoviral, adeno-associated viral vector.
  7. 7. The biomaterial of claim 3, wherein the host cell comprises a prokaryotic cell, a eukaryotic cell.
  8. 8. A complex, characterized in that the complex is a complex obtained by modifying the antibody or the antigen binding fragment thereof according to any one of claims 1-2, wherein the modification is a conjugation modification of a detectable label; The detectable label is a fluorescent dye, avidin, paramagnetic atom, radioisotope, enzyme label, or colloidal gold.
  9. 9. A product comprising the antibody or antigen-binding fragment thereof of any one of claims 1-2, the biomaterial of any one of claims 3-7, or the complex of claim 8.
  10. 10. The product of claim 9, wherein the product comprises a kit, a test strip, a nucleic acid membrane strip, a chip, a system, or a device.
  11. 11. A method of any one of the following, the method comprising: (1) A method for producing the antibody or antigen-binding fragment thereof according to any one of claims 1 to 2, comprising the steps of culturing the host cell according to any one of claims 3 to 7 to obtain a culture product, and isolating and purifying the culture product to obtain the antibody or antigen-binding fragment thereof according to any one of claims 1 to 2; (2) A method of preparing a host cell according to any one of claims 3 to 7, comprising the step of introducing a polynucleotide molecule according to any one of claims 3 to 7 or a vector comprising the same into a host cell.
  12. 12. The method of claim 11, wherein the means of introduction comprises calcium phosphate transfection, DEAE, dextrose-mediated transfection, electroporation, phage infection.
  13. 13. An application of any one of the following, the application comprising: (1) Use of the antibody or antigen-binding fragment thereof of any one of claims 1-2, the biological material of any one of claims 3-7 and/or the complex of claim 8 in the preparation of a product for detecting west nile virus and/or west nile virus E protein; (2) Use of the antibody or antigen binding fragment thereof of any one of claims 1-2, the biological material of any one of claims 3-7, the complex of claim 8 and/or the product of any one of claims 9-10 for the preparation of a product for the diagnosis and/or co-diagnosis of a disease associated with west nile virus infection; (3) Use of an antibody or antigen-binding fragment thereof according to any one of claims 1-2, a biological material according to any one of claims 3-7 and/or a complex according to claim 8 for the manufacture of a medicament for the treatment and/or prevention of diseases associated with west nile virus infection.

Description

Neutralizing antibody WN-XH3 for resisting West Nile virus and application thereof Technical Field The invention belongs to the technical field of biological medicine, relates to an antiviral antibody, and in particular relates to a neutralizing antibody WN-XH3 for resisting West Nile virus and application thereof. Background West Nile Virus (WNV) infection can cause West Nile fever, west Nile viral encephalitis and meningitis, and is a zoonotic, natural and acute infectious disease. No specific drug is available for treating WNV infection, and early discovery is a main measure for controlling WNV transmission. Detection of WNV antigen can be performed by cell culture isolation techniques and plaque titration, conventional RT-PCR, real-time fluorescent RT-PCR, immunohistochemistry, and the like. The method has the advantages of high cost, easy occurrence of false positive results due to sample pollution, long detection period, difficult popularization in large-scale detection due to the requirement of professional technicians and BSL-3 biosafety laboratories, and quick and sensitive detection of WNV antigens by using methods such as antigen capture ELISA, indirect immunofluorescence, immunohistochemistry and the like, and is suitable for being applied to large-scale monitoring systems. The application of antigen capture ELISA, indirect immunofluorescence, immunohistochemistry, etc. detection methods relies on the development of antibodies specific for WNV antigens. Therefore, it is significant to provide an antibody specific for WNV antigen. Disclosure of Invention In order to make up the defects of the prior art, the invention aims to provide an anti-West Nile virus neutralizing antibody WN-XH3 and application thereof. In order to achieve the above purpose, the present invention adopts the following technical scheme: in a first aspect, the invention provides an antibody or antigen-binding fragment thereof against west nile virus. Further, the antibody comprises a heavy chain variable region comprising HCDR1, HCDR2 and HCDR3 in the heavy chain variable region as shown in SEQ ID NO. 1 and a light chain variable region comprising LCDR1, LCDR2 and LCDR3 in the light chain variable region as shown in SEQ ID NO. 3, wherein the determination scheme of the CDR sequence is any one of the IMGT, chothia, kabat, abM schemes. Preferably, the determination scheme of the CDR sequences is the Kabat scheme. "Complementarity determining regions" or "CDR regions" or "CDRs" or "hypervariable regions" are regions of an antibody variable domain that are highly variable in sequence and form structurally defined loops ("hypervariable loops") and/or contain antigen-contacting residues ("antigen-contacting points"). CDRs are mainly responsible for binding to the epitope. Based on the variable region amino acid sequences comprised by a given antibody or fragment thereof of the invention, one skilled in the art can routinely determine the CDRs comprised therein. For example, the CDRs in the variable region amino acid sequence are defined using IMGT scheme, kabat scheme, abM scheme, chothia scheme or Contact scheme. When referring to defining antibodies with specific CDR sequences as defined herein, the scope of the antibodies also encompasses antibodies whose variable region sequences comprise the specific CDR sequences, but whose purported CDR boundaries differ from the specific CDR boundaries defined herein by the application of different schemes (e.g., different assignment system rules or combinations). The CDRs of the antibodies of the invention can be evaluated manually to determine boundaries according to any protocol or combination of protocols in the art. In the present invention, unless otherwise indicated, the term "CDR" or "CDR sequence" encompasses CDR sequences determined in any of the above-described ways. In a specific embodiment of the present invention, the determination scheme of the CDR sequences is an IMGT scheme. Further, the heavy chain variable region comprises the amino acid sequence shown in SEQ ID NO.1, or an amino acid sequence having at least 90% identity to the amino acid sequence shown in SEQ ID NO.1, or a sequence having one or more amino acid substitutions, deletions or insertions, or any combination thereof, as compared to the amino acid sequence shown in SEQ ID NO. 1. Further, the light chain variable region comprises the amino acid sequence shown in SEQ ID NO. 3, or an amino acid sequence having at least 90% identity to the amino acid sequence shown in SEQ ID NO. 3, or a sequence having one or more amino acid substitutions, deletions or insertions, or any combination thereof, as compared to the amino acid sequence shown in SEQ ID NO. 3. In the present invention, the term "identity" refers to sequence similarity to the amino acid sequences used in the present invention. To determine sequence identity, sequence alignments can be performed in a variety of ways known to those skilled in the art, e.g., u