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HIV-1 broadly neutralizing antibody and use thereof

An HIV-1, antibody technology, applied in the direction of antibodies, antibody medical components, applications, etc.

Active Publication Date: 2017-08-08
NAT CENT FOR AIDSSTD CONTROL & PREVENTION CHINESE CENT FOR DISEASE CONTROL & PREVENTION +1
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0003] The monoclonal antibody b12 was first obtained by phage display library technology, but it can only target about 40% of known HIV-1 viruses [1]

Method used

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  • HIV-1 broadly neutralizing antibody and use thereof
  • HIV-1 broadly neutralizing antibody and use thereof
  • HIV-1 broadly neutralizing antibody and use thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0077] Example 1: Identification of broad-spectrum neutralizing antibody DRVIA7

[0078] Antibody DRVIA7 isolated from Chinese HIV-1 infected patients

[0079] The inventor isolated a monoclonal antibody from a sample of a Chinese HIV-1 infected person. It has been identified that the antibody has broad-spectrum neutrality to a variety of HIV-1, and it is named DRVIA7. The Escherichia coli carrying the expression vector (DRVIA7H) of the heavy chain gene and the expression vector (DRVIA7L) of the light chain gene containing the antibody DRVIA7 were deposited in the China General Microorganism Culture Collection Center ( China General Microbiological Culture Collection Center, CGMCC) (No. 3, Yard No. 1, Beichen West Road, Chaoyang District, Beijing). The coding sequence of the heavy chain variable region contained in DRVIA7H is SEQ ID NO:1, and the amino acid sequence of the heavy chain variable region encoded by it is SEQ ID NO:2. The coding sequence of the light chain varia...

Embodiment 2

[0098] Example 2: Modified antibody DRVIA7H+gDRVI01-L57

[0099] Amino Acid Residue Based Energy Estimation

[0100] The inventors performed a residue-based energy evaluation of the complex formed by DRVIA7+gp120 [8] . Such as image 3 As shown, it was found that there may be structural conflicts that interfere with the binding of DRVIA7 to gp120 at the N-terminal, CDRL1 and CDRL3 regions of the light chain variable region of DRVIA7.

[0101] Transformed light chain variable region gDRVI01-L57

[0102] Based on this finding, the inventors made a series of modifications to the light chain of DRVIA7. Various modifications have been made to the CDRL1 region, but the neutralizing ability of the antibody has not been significantly improved. However, when the two N-terminal amino acids of the light chain variable region of DRVIA7 were deleted, it was found that the binding ability and neutralization width of the engineered antibody were greatly improved, and the transformed antib...

Embodiment 3

[0108] Example 3: Antibody DRVIA7H+gDRVI01-L40 was obtained by screening the antibody light chain gene library

[0109] DRVIA7 Antibody Sequence Analysis

[0110] Such as Figure 5 As indicated, the DRVIA7 antibody gene was analyzed using the antibody gene analysis database IMGT V-QEST server (http: / / www.imgt.org / IMGT_vquest / vquest?livret=0&Option=humanIg). The DRVIA7 antibody heavy chain belongs to the IgHV1-02*02 family, and the CDRH3 is 11 amino acids (Kabat nomenclature). The light chain belongs to the IgKV1-5*03 family, and CDRL3 is 5 amino acids. with VRC01 antibody [1] The comparison found that the DRVIA7 antibody and the VRC01 antibody use the same heavy chain family gene, and the length of the light chain CDRL3 is the same as that of VRC01, revealing that the DRVIA7 antibody may belong to the VRC01-like antibody.

[0111] Structural comparative analysis of DRVIA7 and VRC01-like antibodies

[0112] In Example 1, the crystal structure of the DRVIA7 antibody was res...

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Abstract

The present invention relates to a HIV-1 broadly neutralizing antibody which can be specifically bonded with HIV-1gp120. The present invention also relates to a preparation method and use of the HIV-1 broadly neutralizing antibody.

Description

technical field [0001] The present invention relates to HIV-1 broadly neutralizing antibodies that specifically bind HIV-1 gp120. The present invention also relates to the preparation method and application of the antibody. Background technique [0002] HIV-1 neutralizing antibodies can effectively prevent HIV-1 from entering human CD4+ T cells. Therefore, as a treatment for HIV-1 infected persons, the field of AIDS research has been devoting itself to the development of potent HIV-1 broad-spectrum neutralizing antibodies. [0003] The monoclonal antibody b12 was first obtained by phage display library technology, but it can only target about 40% of known HIV-1 viruses [1] . Since 2010, thanks to the development of technologies such as single B cell sorting and deep sequencing, a variety of human monoclonal antibodies with broad-spectrum neutralizing activity against HIV-1 have been isolated from HIV-1 infected patients , such as VRC01 targeting the CD4 binding site [2]...

Claims

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Application Information

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IPC IPC(8): C07K16/10C12N15/13A61K39/42A61P31/18G01N33/577G01N33/569
CPCC07K16/1063C07K2317/54C07K2317/565C07K2317/55C07K2317/56C07K2317/622C07K2317/624A61K39/00A61K39/42C07K2317/21C07K2317/33C07K2317/51C07K2317/515C07K2317/567C07K2317/76C07K2317/92G01N2333/16A61K2039/505A61P31/18
Inventor 邵一鸣朱江李宇星I·A·威尔逊L·孔鞠斌何林玲任莉陈亚静刘建东
Owner NAT CENT FOR AIDSSTD CONTROL & PREVENTION CHINESE CENT FOR DISEASE CONTROL & PREVENTION
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