CN1108819C - Preparation of dissociation-resisting epitope vaccine - Google Patents
Preparation of dissociation-resisting epitope vaccine Download PDFInfo
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- 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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- epitope
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Abstract
本发明属生物工程技术领域，本发明首先人工合成一个或一个以上抗原蛋白上的一个或一个以上特定关键表位上的几个限制性突变型表位的表位多肽；突变型表位以一个或重复的形式出现在人工合成的一条多肽上；表位多肽耦联到载体蛋白或载体多肽或者利用MAP技术系统直接合成为树枝状分子上；表位多肽的耦联物配以适当佐剂制备成抗变异—表位疫苗。本发明能诱导表位特异性的免疫应答；能对付因病原体变异而导致的疫苗失效；能制备多联疫苗。The invention belongs to the technical field of bioengineering. The invention first artificially synthesizes epitope polypeptides of several restricted mutant epitopes on one or more specific key epitopes on one or more antigenic proteins; or repeated forms appear on a synthetic polypeptide; the epitope polypeptide is coupled to the carrier protein or carrier polypeptide or directly synthesized into a dendritic molecule using the MAP technology system; the conjugate of the epitope polypeptide is prepared with an appropriate adjuvant into an anti-variant-epitope vaccine. The invention can induce epitope-specific immune response; can deal with vaccine failure caused by 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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