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Neutralizing antibody for resisting influenza A virus and application thereof

A technology of influenza A virus and influenza A, applied in the direction of antiviral agent, virus/bacteriophage, antiviral immunoglobulin, etc., can solve the problems of not neutralizing or inhibiting influenza A virus infection or remission, and not yet discovered

Inactive Publication Date: 2017-12-01
INSTITUTE FOR RESEARCH IN BIOMEDECINE
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, no influenza A-specific neutralizing antibody targeting an epitope in the HA trimer conserved on all 16 subtypes and able to neutralize viruses of both Group 1 and Group 2 subtypes has been found to date, and Their isolation remains a major goal in therapeutic and vaccine design
[0009] Despite decades of research, there are no marketed antibodies that broadly neutralize or inhibit influenza A virus infection or alleviate disease caused by influenza A virus

Method used

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  • Neutralizing antibody for resisting influenza A virus and application thereof
  • Neutralizing antibody for resisting influenza A virus and application thereof
  • Neutralizing antibody for resisting influenza A virus and application thereof

Examples

Experimental program
Comparison scheme
Effect test

preparation example Construction

[0102] Antibody preparation

[0103] Antibodies according to the invention can be prepared by any method known in the art. Common methods for the production of monoclonal antibodies, eg using hybridoma technology, are known (Kohler, G. and Milstein, C, 1975; Kozbar et al. 1983). In one example, the alternative EBV immortalization method described in WO2004 / 076677 is used.

[0104] B cells producing antibodies of the invention can be transformed with EBV in the presence of polyclonal B cell activators using the methods described in WO2004 / 076677. Transformation with EBV is a standard technique and can be easily adapted to include polyclonal B cell activators.

[0105] Optionally, additional stimulators of cell growth and cell differentiation can be added during the transformation step to further increase efficiency. These stimuli can be cytokines such as IL-2 and IL-15. In one aspect, IL-2 is added during the immortalization step to further improve the efficiency of immor...

example

[0188] Exemplary embodiments of the invention are provided in the following examples. The following examples are given by way of illustration only and to assist those of ordinary skill in using the invention. The examples are not intended to otherwise limit the scope of the invention in any way.

example 1

[0189] Example 1: Generation and Characterization of Influenza A Broadly Neutralizing Antibodies from Plasma Cells

[0190] To identify individuals who can develop heterosubtypic antibodies in response to seasonal influenza vaccines (containing H1 and H3 HA), we directed circulating plasma cells collected on day 7 after boost to secrete conjugate vaccine or unrelated H5 The ability of the antibody to HA (A / VN / 1203 / 04) was screened by ELISPOT. Surprisingly, however, no H5-specific plasma cells were detected in 4 of 5 donors tested, and 14% of IgG-secreting plasma cells in one donor produced antibodies against H5, And 57 percent developed antibodies against the vaccine. CD138+ plasma cells were isolated from peripheral blood mononuclear cells (PBMC) collected on day 7 post-vaccination by using magnetic microbeads followed by cell sorting using a FACSAria instrument. A limited number of plasma cells are seeded into microwell culture plates. Culture supernatants were tested i...

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PUM

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Abstract

The invention relates to an antibody or an antigen-binding fragment thereof that specifically binds to an epitope in the stem region of an influenza A hemagglutinin trimer and neutralizes group 1 subtype and group 2 subtype. The invention also relates to nucleic acids encoding the antibody or antibody fragment, immortalized B cells producing the antibody or antibody fragment, and cultured single plasma cells, and relates to the epitopes binding the antibody or antibody fragment. In addition, the invention relates to application of the antibody, antibody fragment and epitope in screening methods and in diagnosis, treatment and prevention of influenza A virus infection.

Description

[0001] This application is a divisional application, the Chinese application number of its parent case is 201180072356.0, the international application number is PCT / IB2011 / 002329, and the filing date is July 18, 2011. Background technique [0002] Neutralizing antibody responses to influenza A viruses are usually specific for a given virus subtype. There are 16 influenza A subtypes defined by their hemagglutinin ("HA") proteins. These 16 HAs (H1 – H16) can be divided into two groups. Group 1 consists of subtypes H1, H2, H5, H6, H8, H9, H11, H12, H13, and H16, and group 2 includes subtypes H3, H4, H7, H10, H14, and H15. Although all subtypes are present in birds, mainly the H1, H2 and H3 subtypes cause disease in humans. The H5, H7 and H9 subtypes are causing sporadic severe infections in humans and may generate new pandemics. H1 and H3 viruses are constantly evolving to produce new variants, a phenomenon known as antigenic drift. Antibodies raised in response to previous ...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07K16/10C12N15/13C07K14/11A61K39/42A61P31/16
CPCA61K2039/505C07K14/005C07K16/1018C07K2317/14C07K2317/21C07K2317/33C07K2317/34C07K2317/56C07K2317/565C07K2317/76C07K2317/92C12N2760/16122G01N33/56983G01N2333/11G01N2469/10
Inventor A.兰扎韦基亚
Owner INSTITUTE FOR RESEARCH IN BIOMEDECINE