CN102727889A - Application of specific antibodies in preparation of biological products for controlling virus infection based on virus acceptor binding site selection - Google Patents
Application of specific antibodies in preparation of biological products for controlling virus infection based on virus acceptor binding site selection Download PDFInfo
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- CN102727889A CN102727889A CN2012102072062A CN201210207206A CN102727889A CN 102727889 A CN102727889 A CN 102727889A CN 2012102072062 A CN2012102072062 A CN 2012102072062A CN 201210207206 A CN201210207206 A CN 201210207206A CN 102727889 A CN102727889 A CN 102727889A
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Abstract
The invention discloses an application of specific antibodies in the preparation of biological products for controlling virus infection based on virus acceptor binding site selection. The heavy chain variable gene VH of the specific antibodies comprises one or more CDRs in amino acid sequences containing GYNFASEW, IYPGDSDT and ARQNHYGSGSYFYRTAYYYAMDV, the heavy chain variable gene VL of the specific antibodies comprises one or more CDRs in amino acid sequences containing QSISSY, AAS and QQSYNTPFT, and the specific antibodies having above amino acid sequence are selectively combined with gp41MPER. According to the invention, the specific antibodies having specific sequences are selectively combined with the gp41MPER, so the antibodies and viruses undergo a good neutral reaction, thereby the antibodies play good roles in the control of the virus infection.
Description
Technical field
The invention belongs to biological field, particularly, relate to a kind of based on the application of the specific antibody of selecting the virus receptor binding site in the biological product of preparation control viral infection.
Background technology
Along with the continuous development of World Economics, spatial distance no longer becomes the obstacle that people link up, but is accompanied by this progress, the infectious disease various places also all over the world that caused by various viruses.Wherein be that the harm that causes of the AIDS of the cause of disease is the most noticeable with the retrovirus, annual all have millions of population to die from AIDS.
Neutralizing antibody has a vital status on what resist viral infection.The process that retrovirus gets into cell comprises absorption, receptors bind, and film merges and then viral inclusions is mainly nucleic acid and enzyme transports in the cell.Thereby neutralizing antibody can combine the albumen of virus surface to stop virus to get into cell.The effective object of neutralizing antibody is the envelope protein of virus normally, and some one of them important target spot of virus is the fusion rotein subunit gp41 that is positioned at the envelope protein on virion surface.
Have a lot of research worker intentions to produce similar neutralizing antibody for a long time, but successful example rarely have report through various antigen induction mechanism.Researcheres are recognized for slow virus gradually, are conformation type antibody mostly with antibody wherein.Relevant vaccine design research in the past mainly concentrates on the 2F5 action target spot, but does not almost obtain corresponding neutralizing antibody.A kind of explanation thinks that these vaccines are not placed on this section 2F5 recognition sequence in the suitable environment, therefore can not present out correct conformation.
Summary of the invention
Technical problem to be solved by this invention provides a kind of based on the application of the specific antibody of selecting the virus receptor binding site in the biological product of preparation control viral infection.The specific antibody of the specific amino acids sequence through will having the application record optionally is incorporated into gp41 MPER, can make antibody and virus that neutralization reaction preferably takes place, and plays the effect of better prevention viral infection.
The present invention solves the problems of the technologies described above the technical scheme that is adopted: based on the application of the specific antibody of selecting the virus receptor binding site in the biological product of preparation control viral infection; Said specific antibody heavy chain variable region gene VH comprises aminoacid, and to contain sequence be the one or more CDRs among GYNFASEW, IYPGDSDT, the ARQNHYGSGSYFYRTAYYYAMDV; Specific antibody chain variable region gene VL comprises aminoacid, and to contain sequence be the one or more CDRs among QSISSY, AAS, the QQSYNTPFT, and the specific antibody with this aminoacid sequence optionally is incorporated into gp41 MPER.
The application's virus is example with HIV-1, and its peplos is from host cell membrane, and two kinds of glycoprotein gp120 and gp41 in the peplos are the important antigen signs of virus, by the env gene code.The gp160 molecule is a glycoprotein precursor, and cleavable is gp120 and gp41.The Gp120 molecule is claimed outer membrane protein, can combine with T cell CD4 molecular specificity and discerns target cell.Gp41 is embedded in the peplos when flat, and when gp120 combined with the CD4 molecule, the gp120 occurred conformation changed, and exposed the binding site of virus auxiliary receptor, then with after accessory receptor combines, and gp41 mediation virus and cd4 cell fusion, thereby in the viral entering cell.The immunogenicity of virus surface envelope protein is stronger than viral core protein.Almost can detect antibody in 97% ~ 100% HIV sufferers's serum to gp120, gp160.Gp41 antibody is stable and lasting, to the diagnosis of virus with prevent and treat significant.Find through the heavy chain variable region gene VH of more different specific antibodies and the amino acid sequence of chain variable region gene VL; Variation only concentrates on the aminoacid of few regions wherein (15%～20%); Be called hypervariable region, hypervariable region is that the antigen of antibody combines the position, with the complementary structure of antigenic determinant; So be called again complementary determining region (complementarity-determining regions, CDRs).The application has carried out correlational study with the gp41MPER zone as target spot: because gp41MPER is difficult under the albumen skeleton of gp41 background own, produce specific immunity; So merge through albumen; And simulation gp41 strides the native conformation in the preceding territory of film (MPER) in immunologic process; The epi-position that this is regional is passs immune system, is directed against the regional specific antibody of gp41MPER in the hope of obtaining, and analyzes the neutralization activity of the antibody that obtains.
Said heavy chain variable region gene VH comprises aminoacid and contains three CDRs that sequence is GYNFASEW, IYPGDSDT, ARQNHYGSGSYFYRTAYYYAMDV, and chain variable region gene VL comprises aminoacid and contains three CDRs that sequence is QSISSY, AAS, QQSYNTPFT.
Particularly, said biological product are bio-carrier.
Perhaps, said biological product are biological fragment.
Perhaps, said biological product are antibody.
The invention has the beneficial effects as follows: the present invention optionally is incorporated into gp41 MPER through the specific antibody that will have particular sequence, can make antibody and virus that neutralization reaction preferably takes place, and plays the effect of better prevention viral infection.
The specific embodiment
Below in conjunction with the specific embodiment the present invention is made further detailed description, but embodiment of the present invention is not limited only to following embodiment.
The ability instance is based on the application of the specific antibody of selecting the virus receptor binding site in the biological product of preparation control viral infection; Said specific antibody heavy chain variable region gene VH comprises aminoacid and contains three CDRs that sequence is GYNFASEW, IYPGDSDT, ARQNHYGSGSYFYRTAYYYAMDV, and specific antibody chain variable region gene VL comprises aminoacid and contains three CDRs that sequence is QSISSY, AAS, QQSYNTPFT.
The monoclonal antibody of present embodiment, variable heavy chain that has and variable sequence of light chain, the concrete sequence of heavy chain variable region gene VH is:
Gln?Met?Gln?Leu?Val?Gln?Ser?Gly?Ala?Glu?Val?Lys?Lys?Pro?Gly?Glu?
Ser?Leu?Lys?Ile?Ser?Cys?Lys?Val?Ser?Gly?Tyr?Asn?Phe?Ala?Ser?Glu?
Trp?Ile?Gly?Trp?Val?Arg?Gln?Met?Pro?Gly?Lys?Gly?Leu?Glu?Trp?Met?
Gly?Ile?Ile?Tyr?Pro?Gly?Asp?Ser?Asp?Thr?Lys?Tyr?Ser?Pro?Ser?Phe?
Gln?Gly?Gln?Val?Ile?Ile?Ser?Ala?Asp?Lys?Ser?Ile?Asn?Thr?Ala?Tyr?
Leu?Gln?Trp?Ser?Ser?Leu?Lys?Ala?Ser?Asp?Thr?Ala?Ile?Tyr?Tyr?Cys?
Ala?Arg?Gln?Asn?His?Tyr?Gly?Ser?Gly?Ser?Tyr?Phe?Tyr?Arg?Thr?Ala?
Tyr?Tyr?Tyr?Ala?Met?Asp?Val?Trp?Gly?Gln?Gly?Thr?Thr?Val?Thr?Val?
Ser?Ser?
The amino acid whose concrete sequence of chain variable region gene VL is:
Val?Ala?Gln?Ala?Ala?Asp?Ile?Gln?Leu?Thr?Gln?Ser?Pro?Ser?Ser?Leu?
Ser?Ala?Ser?Val?Gly?Asp?Arg?Val?Thr?Ile?Thr?Cys?Arg?Ala?Ser?Gln?
Ser?Ile?Ser?Ser?Tyr?Leu?Asn?Trp?Tyr?Gln?Gln?Lys?Pro?Gly?Lys?Ala?
Pro?Asn?Leu?Leu?Ile?Tyr?Ala?Ala?Ser?Ser?Leu?Gln?Ser?Gly?Val?Pro?
Ser?Arg?Phe?Ser?Gly?Ser?Gly?Ser?Gly?Thr?Asp?Phe?Thr?Leu?Thr?Ile?
Ser?Ser?Leu?Gln?Pro?Glu?Asp?Phe?Ala?Thr?Tyr?Tyr?Cys?Gln?Gln?Ser?
Tyr?Asn?Thr?Pro?Phe?Thr?Leu?Gly?Pro?Gly?Thr?Lys?Val?Glu?Ile?Lys?
Arg?
Following table 1 is the aminoacid sequence in the fixed CDR of present embodiment zone
The CDR zone of table 1. monoclonal antibody VH and VL
Monoclonal antibody through measuring present embodiment is for the neutrality of virus, and the result shows that the monoclonal antibody with this aminoacid sequence is preferable to the neutrality effect of virus.
Table 2. is to a series of virus strains, in the present embodiment monoclonal antibody with the activity experiment result
Can know by above-mentioned experimental result; Through before human body contact virus or behind the infective virus, in human body, injecting monoclonal antibody of the present invention (fragment); Perhaps comprise compositions, medicine of this monoclonal antibody etc.; Can effectively suppress the infection of virus, thereby suppress the viral infection T lymphocytes in human body to greatest extent human body.Virus in the present embodiment is HIV-1 virus.
Aforesaid antibody and fragment can be formulated as a composition (for example a kind of drug ingredient).Appropriate ingredients comprises dissolving or is dispersed in the antibody (or antibody fragment) in the acceptable carrier that makes up a prescription (for example a kind of water-soluble medium).This composition can be aseptic injection form.Antibody (and fragment) also can be formulated as the composition that is fit to skin or mucosa topical.Such composition can be liquid, ointment, emulsifiable paste, gel and patch.
As stated, embodiment of the present invention preferably.
Claims (5)
1. based on the application of the specific antibody of selecting the virus receptor binding site in the biological product of preparation control viral infection; It is characterized in that; Said specific antibody heavy chain variable region gene VH comprises aminoacid, and to contain sequence be the one or more CDRs among GYNFASEW, IYPGDSDT, the ARQNHYGSGSYFYRTAYYYAMDV; Specific antibody chain variable region gene VL comprises aminoacid, and to contain sequence be the one or more CDRs among QSISSY, AAS, the QQSYNTPFT, and the specific antibody with this aminoacid sequence optionally is incorporated into gp41 MPER.
2. application according to claim 1; It is characterized in that; Said heavy chain variable region gene VH comprises aminoacid and contains three CDRs that sequence is GYNFASEW, IYPGDSDT, ARQNHYGSGSYFYRTAYYYAMDV, and chain variable region gene VL comprises aminoacid and contains three CDRs that sequence is QSISSY, AAS, QQSYNTPFT.
3. application according to claim 1 and 2 is characterized in that, said biological product are bio-carrier.
4. application according to claim 1 and 2 is characterized in that, said biological product are biological fragment.
5. application according to claim 1 and 2 is characterized in that, said biological product are antibody.
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| Application Number | Priority Date | Filing Date | Title |
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| CN2012102072062A CN102727889A (en) | 2012-06-21 | 2012-06-21 | Application of specific antibodies in preparation of biological products for controlling virus infection based on virus acceptor binding site selection |
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| CN2012102072062A CN102727889A (en) | 2012-06-21 | 2012-06-21 | Application of specific antibodies in preparation of biological products for controlling virus infection based on virus acceptor binding site selection |
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Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2022019340A1 (en) * | 2020-07-22 | 2022-01-27 | 国立大学法人九州大学 | Antibody and use thereof |
-
2012
- 2012-06-21 CN CN2012102072062A patent/CN102727889A/en active Pending
Non-Patent Citations (1)
| Title |
|---|
| ZHONGYU ZHU等: "《Cross-Reactive HIV-1-Neutralizing Human Monoclonal Antibodies Identified from a Patient with 2F5-Like Antibodies》", 《JOURNAL OF VIROLOGY》 * |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2022019340A1 (en) * | 2020-07-22 | 2022-01-27 | 国立大学法人九州大学 | Antibody and use thereof |
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Application publication date: 20121017 |