CN1108819C - Preparation of dissociation-resisting epitope vaccine - Google Patents
Preparation of dissociation-resisting epitope vaccine Download PDFInfo
- Publication number
- CN1108819C CN1108819C CN 99123806 CN99123806A CN1108819C CN 1108819 C CN1108819 C CN 1108819C CN 99123806 CN99123806 CN 99123806 CN 99123806 A CN99123806 A CN 99123806A CN 1108819 C CN1108819 C CN 1108819C
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- Prior art keywords
- epitope
- polypeptide
- vaccine
- dissociation
- resisting
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- 229960005486 vaccine Drugs 0.000 title claims abstract description 30
- 238000002360 preparation method Methods 0.000 title claims description 12
- 108090000765 processed proteins & peptides Proteins 0.000 claims abstract description 25
- 229920001184 polypeptide Polymers 0.000 claims abstract description 24
- 102000004196 processed proteins & peptides Human genes 0.000 claims abstract description 24
- 239000002671 adjuvant Substances 0.000 claims abstract description 6
- 108091007433 antigens Proteins 0.000 claims abstract description 6
- 102000036639 antigens Human genes 0.000 claims abstract description 5
- 102000014914 Carrier Proteins Human genes 0.000 claims abstract description 3
- 108010078791 Carrier Proteins Proteins 0.000 claims abstract description 3
- 230000008878 coupling Effects 0.000 claims description 5
- 238000010168 coupling process Methods 0.000 claims description 5
- 238000005859 coupling reaction Methods 0.000 claims description 5
- 239000000412 dendrimer Substances 0.000 claims description 5
- 229920000736 dendritic polymer Polymers 0.000 claims description 5
- 230000035772 mutation Effects 0.000 claims description 5
- 244000052769 pathogen Species 0.000 abstract description 10
- 230000001717 pathogenic effect Effects 0.000 abstract description 9
- 239000000126 substance Substances 0.000 abstract description 2
- 230000028993 immune response Effects 0.000 abstract 1
- 230000004044 response Effects 0.000 description 4
- 108090000623 proteins and genes Proteins 0.000 description 3
- 241000555268 Dendroides Species 0.000 description 2
- 241000725303 Human immunodeficiency virus Species 0.000 description 2
- 241000713772 Human immunodeficiency virus 1 Species 0.000 description 2
- 230000009849 deactivation Effects 0.000 description 2
- 230000000694 effects Effects 0.000 description 2
- 238000005516 engineering process Methods 0.000 description 2
- 238000004519 manufacturing process Methods 0.000 description 2
- 238000000034 method Methods 0.000 description 2
- 102000039446 nucleic acids Human genes 0.000 description 2
- 108020004707 nucleic acids Proteins 0.000 description 2
- 150000007523 nucleic acids Chemical class 0.000 description 2
- 102000004169 proteins and genes Human genes 0.000 description 2
- 229940031626 subunit vaccine Drugs 0.000 description 2
- LLXVXPPXELIDGQ-UHFFFAOYSA-N (2,5-dioxopyrrolidin-1-yl) 3-(2,5-dioxopyrrol-1-yl)benzoate Chemical compound C=1C=CC(N2C(C=CC2=O)=O)=CC=1C(=O)ON1C(=O)CCC1=O LLXVXPPXELIDGQ-UHFFFAOYSA-N 0.000 description 1
- 208000035473 Communicable disease Diseases 0.000 description 1
- 241000991587 Enterovirus C Species 0.000 description 1
- 108010003533 Viral Envelope Proteins Proteins 0.000 description 1
- 230000005875 antibody response Effects 0.000 description 1
- 239000000427 antigen Substances 0.000 description 1
- 230000001580 bacterial effect Effects 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 229940028617 conventional vaccine Drugs 0.000 description 1
- 201000010099 disease Diseases 0.000 description 1
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 1
- 208000015181 infectious disease Diseases 0.000 description 1
- 230000002265 prevention Effects 0.000 description 1
- 230000001681 protective effect Effects 0.000 description 1
- 210000002966 serum Anatomy 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 241000712461 unidentified influenza virus Species 0.000 description 1
Landscapes
- Peptides Or Proteins (AREA)
- Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
Abstract
The present invention belongs to the technical field of biological engineering. In the present invention, firstly, the epitope polypeptide of a plurality of restrictive saltant epitopes of one or a plurality of specific critical epitopes of one or a plurality of antigen proteins are artificially synthesized; one or a plurality of saltant epitopes are present to one polypeptide artificially synthesized; the epitope polypeptide is coupled to the carrier protein or the carrier polypeptide or directly synthesized into dendritic molecules by using an MAP technological system; the coupled substance of the epitope polypeptide is added with proper adjuvant to prepare the dissociation-resisting epitope vaccine. The present invention can induce the immune response of the epitope specificity, can cope with vaccine failure induced by the pathogen variation, and can prepare multiple vaccines.
Description
The invention belongs to technical field of bioengineering, particularly the preparation of epiposition vaccine and production.
The conventional vaccine technology of preparing adopts following method usually:
(1) utilizes the pathogen (as poliovirus) of attenuation or deactivation;
(2) utilize the related component natural or gene recombinaton of pathogen, as the subunit vaccine of preparations such as bacterial toxoid, virus envelope protein;
(3) utilize the nucleic acids for preparation vaccine of pathogen.
Existing these vaccine production technology exist very big difficulty when preventing the infectious disease that is caused by some very high pathogen of variation frequency (as HIV (human immunodeficiency virus) and influenza virus); In addition, currently available vaccines, existing vaccines can not directly be induced the immunne response of predetermined epitope specificity.
The objective of the invention is in order to solve or partly solve the global problem that the pathogen variation causes vaccine failure, the preparation method of a kind of dissociation-resisting epitope vaccine of designing makes it have pathogen or the native protein of pathogen or the nucleic acid of gene recombinant protein antigen and pathogen that does not need attenuation or deactivation; Can directly induce the immunne response of predetermined epitope specificity; The vaccine failure that can tackle due to illness substance variation and cause; Can prepare the outstanding advantages such as multiple vaccines of prevention different pathogens.
The preparation method of the dissociation-resisting epitope vaccine that the present invention proposes is characterized in that may further comprise the steps:
1) epitope polypeptide of the several restrictive mutation type epi-positions on one or more the specific critical epitopes on one or more antigen proteins of synthetic;
2) said one or more saltant epi-positions are with one or appear at multiple form on the polypeptide (being multimutation type epi-position-epitope polypeptide) of synthetic;
3) this epitope polypeptide is coupled to carrier protein or carrier polypeptide or utilizes MAP (Multiple AntigenPeptide) technological system directly to synthesize on the dendrimer;
4) coupling matter of epitope polypeptide or dendrimer are equipped with that proper adjuvant is prepared into dissociation-resisting epitope vaccine or resistance is different-multiepitope epitope vaccine.
The present invention has following effect according to the preparation method of the epiposition vaccine that the brand-new theory (Immunology Today, 20:588-589, in December, 1999) of the epiposition vaccine that is proposed at first by the inventor is designed:
The first, can induce very strong immunne response at defined epitope, compare with corresponding subunit vaccine, can significantly improve antibody horizontal (10-20 is doubly) at defined epitope;
Second, defined epitope on some native protein can not induce the stronger immunne response with protective action in body, the vaccine that utilizes the present invention to prepare can induce the antibody (the antibody amount of epitope specificity is every milliliter of serum of 10-240 microgram) of the epitope specificity of high titre, can play effective immune protection effect;
The 3rd, the resistance of using the present invention's preparation is different-and multiepitope epitope vaccine can induce the antibody response at a plurality of restrictive mutation form variation epi-positions simultaneously in body.
Embodiment one: preparation HIV-1 resistance is different-and multiepitope epitope vaccine
The synthetic two kinds of dissociation-resisting epitope polypeptide that contain four and three restrictive mutation types respectively of step 1.
CG(ELDKWA)G(ELEKWA)G(ELNKWA)G(ELDNWA)
CG(GPGRAFY)G(GPGKAFY)G(GPGQAFY)
Step 2. utilizes MBS (m-maleimidobenzoyl-N-hydroxy succinimide ester) with two kinds of different epitope polypeptides of resistance
Perhaps mix behind the coupling connection respectively with BSA mixed back and carrier protein BSA coupling connection;
Step 3. is mixed with into dissociation-resisting epitope vaccine with adjuvant respectively with coupling matter.
Embodiment two: adopt dendroid epitope polypeptide molecule to prepare the HIV-1 dissociation-resisting epitope vaccine
Step 1. adopts direct synthesis technique to utilize MAP (Multiple Antigen Peptide) technological system directly synthetic
Contain on the dendrimer of four kinds of limited saltants of a defined epitope ELDKWA;
Step 2. is mixed with into the dissociation-resisting epitope epidemic disease with synthetic dendroid epitope polypeptide molecule with proper adjuvant
Seedling.
Claims (2)
1, a kind of preparation method of dissociation-resisting epitope vaccine is characterized in that may further comprise the steps:
1) epitope polypeptide of the several restrictive mutation type epi-positions on one or more the specific critical epitopes on one or more antigen proteins of synthetic;
2) said or a plurality of saltant epi-positions are with one or appear at multiple form on the polypeptide of synthetic;
3) said epitope polypeptide is coupled to carrier protein or carrier polypeptide;
4) coupling matter of said epitope polypeptide is equipped with that proper adjuvant is prepared into dissociation-resisting epitope vaccine or resistance is different-multiepitope epitope vaccine.
2, a kind of preparation method of dissociation-resisting epitope vaccine is characterized in that may further comprise the steps:
1) epitope polypeptide of the several restrictive mutation type epi-positions on one or more the specific critical epitopes on one or more antigen proteins of synthetic;
2) said one or more saltant epi-positions are with one or appear at multiple form on the polypeptide of synthetic;
3) said epitope polypeptide utilizes the MAP technological system directly to synthesize on the dendrimer;
4) dendrimer of said epitope polypeptide is equipped with that proper adjuvant is prepared into dissociation-resisting epitope vaccine or resistance is different-multiepitope epitope vaccine.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN 99123806 CN1108819C (en) | 1999-11-12 | 1999-11-12 | Preparation of dissociation-resisting epitope vaccine |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN 99123806 CN1108819C (en) | 1999-11-12 | 1999-11-12 | Preparation of dissociation-resisting epitope vaccine |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN1256149A CN1256149A (en) | 2000-06-14 |
| CN1108819C true CN1108819C (en) | 2003-05-21 |
Family
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Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN 99123806 Expired - Fee Related CN1108819C (en) | 1999-11-12 | 1999-11-12 | Preparation of dissociation-resisting epitope vaccine |
Country Status (1)
| Country | Link |
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| CN (1) | CN1108819C (en) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US9196800B2 (en) | 1996-06-26 | 2015-11-24 | Osram Gmbh | Light-radiating semiconductor component with a luminescence conversion element |
Families Citing this family (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102391375A (en) * | 2011-10-24 | 2012-03-28 | 武汉伊艾博科技有限公司 | Method for producing antibody by coupling multi-polypeptide epitope of protein antigen with carrier |
-
1999
- 1999-11-12 CN CN 99123806 patent/CN1108819C/en not_active Expired - Fee Related
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US9196800B2 (en) | 1996-06-26 | 2015-11-24 | Osram Gmbh | Light-radiating semiconductor component with a luminescence conversion element |
Also Published As
| Publication number | Publication date |
|---|---|
| CN1256149A (en) | 2000-06-14 |
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