CN105497886A - Application of HBcAg (hepatitis B core antigen) virus-like particle serving as cancer therapeutic vaccine carrier - Google Patents
Application of HBcAg (hepatitis B core antigen) virus-like particle serving as cancer therapeutic vaccine carrier Download PDFInfo
- Publication number
- CN105497886A CN105497886A CN201510972747.8A CN201510972747A CN105497886A CN 105497886 A CN105497886 A CN 105497886A CN 201510972747 A CN201510972747 A CN 201510972747A CN 105497886 A CN105497886 A CN 105497886A
- Authority
- CN
- China
- Prior art keywords
- virus
- hbcag
- particle
- hepatitis
- core antigen
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Pending
Links
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K39/00—Medicinal preparations containing antigens or antibodies
- A61K39/12—Viral antigens
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N15/00—Mutation or genetic engineering; DNA or RNA concerning genetic engineering, vectors, e.g. plasmids, or their isolation, preparation or purification; Use of hosts therefor
- C12N15/09—Recombinant DNA-technology
- C12N15/63—Introduction of foreign genetic material using vectors; Vectors; Use of hosts therefor; Regulation of expression
- C12N15/66—General methods for inserting a gene into a vector to form a recombinant vector using cleavage and ligation; Use of non-functional linkers or adaptors, e.g. linkers containing the sequence for a restriction endonuclease
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K39/00—Medicinal preparations containing antigens or antibodies
- A61K2039/51—Medicinal preparations containing antigens or antibodies comprising whole cells, viruses or DNA/RNA
- A61K2039/525—Virus
- A61K2039/5258—Virus-like particles
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K39/00—Medicinal preparations containing antigens or antibodies
- A61K2039/60—Medicinal preparations containing antigens or antibodies characteristics by the carrier linked to the antigen
- A61K2039/6031—Proteins
- A61K2039/6075—Viral proteins
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N2710/00—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA dsDNA viruses
- C12N2710/00011—Details
- C12N2710/20011—Papillomaviridae
- C12N2710/20034—Use of virus or viral component as vaccine, e.g. live-attenuated or inactivated virus, VLP, viral protein
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Genetics & Genomics (AREA)
- Chemical & Material Sciences (AREA)
- Engineering & Computer Science (AREA)
- General Engineering & Computer Science (AREA)
- Wood Science & Technology (AREA)
- Organic Chemistry (AREA)
- Zoology (AREA)
- Microbiology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- General Health & Medical Sciences (AREA)
- Biotechnology (AREA)
- Biomedical Technology (AREA)
- Molecular Biology (AREA)
- Virology (AREA)
- Animal Behavior & Ethology (AREA)
- Immunology (AREA)
- Veterinary Medicine (AREA)
- Biophysics (AREA)
- Public Health (AREA)
- Physics & Mathematics (AREA)
- Plant Pathology (AREA)
- Medicinal Chemistry (AREA)
- Epidemiology (AREA)
- Pharmacology & Pharmacy (AREA)
- Biochemistry (AREA)
- Mycology (AREA)
- Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
- Peptides Or Proteins (AREA)
Abstract
The invention relates to the field of molecular biology and immunology, in particular to an application of an HBcAg (hepatitis B core antigen) virus-like particle serving as a cervical cancer therapeutic vaccine carrier. A preparation method comprises steps as follows: an HPV16 E749-57CTLs epitope peptide fragment is selected, a DNA (deoxyribose nucleic acid ) fragment of the HPV16 E749-57CTLs epitope peptide fragment is inserted between 78 and 79 amino acids of the HBcAg through genetic recombination, an obtained recombinant plasmid pHBcAg-E749-57 is converted into Escherichia coli DH5alpha, and an HBcAg virus-like particle vaccine presenting E749-57 is obtained after induction expression and purification. After a tumor-bearing mouse is immunized with the virus-like particle vaccine, the body of the mouse can be induced to generate a higher HPV16E7 specific cellular immunologic response, and growth of tumors is remarkably inhibited.
Description
Technical field
The present invention relates to molecular biology and field of immunology, a kind of hepatitis B virus core antigen virus-like particle (HBcAg) is as the construction method of tumor therapeutic vaccine carrier and application thereof specifically.
Background technology
Cervical cancer is that prestige does harm to one of WomanHealth disease the most serious, in female tumor sickness rate, account for second.In worldwide, nearly 49.3 ten thousand new cases and 27.4 ten thousand deaths every year, and in all cases of cervical cancer, the existence of HPV nearly all can be detected.HPV infects and also causes anus cancer, carcinoma vulvae, cancer of vagina and carcinoma of penis, and in addition, HPV infection is also the major reason of the non-reproductive tract carcinogenesis such as head and neck cancer.The persistent infection of clear and definite high-risk HPV is now the necessary factor that cervical cancer occurs and exists.And in high-risk HPV, 16,18 types are relevant to the cervical cancer of 70%.Although business-like preventative HPV vaccine can be induced effective antibody mediated immunity to reply and be produced significant protective effect for the infection of specific HPV type as most high-risk HPVs such as HPV16 and 18 in the world; but it infects or tumor for the HPV set up, and does not have obvious therapeutic effect.Therefore, development therapeutic HPV vaccine, carries out immunization therapy for precancerous lesion and tumor, has the broad prospect of application controlled HPV treating correlative diseases.
HPVE6, E7 cause cell the key factor transformed to occur, continuous expression in cervical cancer cell, and therefore the immunne response of being induced strong special T cell mediation by targeting E6 and E7 is mainly devoted in the research of therapeutic HPV vaccine at present.Strategy comprises: 1) epitope amino acid modifies to strengthen the affinity with MHC molecule; 2) Modified antigen transformation is to instruct its processing submission approach and efficiency; 3) introduce cytokine, chemotactic factor, costimulatory molecules develops to required type to strengthen and to control immunne response; 4) vaccine delivery approach and immune programme for children is optimized; And 5) utilize antigenic peptides/albumen, antibacterial and the different vaccine form such as virus live vector, nucleic acid and cell.But, produce effective clinical therapeutic efficacy without any therapeutic HPV vaccine for patient CIN or tumor patient so far.Therefore, we need badly one tumour immunity suppress and immunologic escape microenvironment under can the candidate vaccine of tumor specific cell immunne response of inducing potent.
Applying effective carrier, to strengthen the immunogenicity of specific antigen be important vaccinology means.Hepatitis B virus core antigen (HBcAg) can escherichia coli
e.coliin effective self assembly become virus-like particle, and the inherent characteristics of its structure makes it have very strong immunogenicity and can produce the specific antibody of high titre.Therefore HBcAg granule become one widely used present heterologous antigen and elicit humoral immune response strong vaccine carrier.In addition, the HBcAg virus-like particle presenting autoinducer molecule and antigenic peptides can tolerate by break immune, induces special autoantibody and the pathologic effect that the target molecule of successful intervention functions disorder causes in disease model.But whether HBcAg virus-like particle has as therapeutic vaccine carrier and promotes that the potential of the cellullar immunologic response of antigen-specific is determined not yet.
This research is intended to inquire into the HBcAg virus sample particle vaccines presenting HPV16E7CTLs pattern epi-position and whether has the cellullar immunologic response of inducing tumor-specific and the ability of Tumor suppression growth, specifies the potential of HBcAg virus-like particle as therapeutic vaccine carrier.
Summary of the invention
Coding E7
49-57positive and negative oligonucleotide fragment annealing renaturation obtain DNA fragmentation, and be connected into hepatitis B virus core antigen HBcAg the 78th and 79 between aminoacid with genetic engineering means, recombinant plasmid transformed is entered picking positive recombinant after escherichia coli Dh5 α, extract plasmid and carry out order-checking and identifies.
By pHBcAg-E7
49-57recombinant plasmid transformed enters Dh5 α competent cell, with IPTG abduction delivering recombiant protein HBcAg-E7
49-57, expression product collects the recombiant protein in supernatant after ultrasonication.Recombiant protein carries out purification through the sucrose density gradient centrifugation of ammonium sulfate salting-out process and 10% ~ 50%.The recombiant protein of purification carries out HPLC analysis, according to appearance time qualification recombiant protein whether assembling assembly virus-like particle and purity thereof.In addition, by electron microscopic observation assembling assembly virus-like particle (VLPs) with unassembled become the recombiant protein form of virus-like particle (non-VLPs).
By this virus-like particle with therapeutic strategies immune mouse, observe mice tumors grew situation, find with HBcAg-E7
49-57after the form immunity of virus-like particle, mice tumors grew is significantly inhibited; After observation time point terminates, collect the mouse spleen after immunity, carry out the lymphocyte number that ELISPOT detects secretion of gamma-IFN, find with HBcAg-E7
49-57after virus-like particle immunity, in Mice Body, create the lymphocyte number of the secretion of gamma-IFN of higher level.
The experiment of application immunological memory detects HBcAg-E7
49-57virus sample particle vaccines is to the protectiveness persistent period of mice; find that mice still exists immunological memory response after the third immunization for 15 weeks; after mouse inoculation tumor cell, ELISPOT detection display vaccine group significantly improves the lymphocyte level of secretion of gamma-IFN.
Accompanying drawing explanation
Fig. 1 shows recombiant plasmid pHBcAg-E7
49-57plasmid construction collection of illustrative plates;
Fig. 2 shows SDS-PAGE and analyzes recombiant protein HBcAg-E7
49-57abduction delivering;
Fig. 3 shows recombiant protein HBcAg-E7
49-57the SDS-PAGE of sucrose density gradient centrifugation analyzes;
Fig. 4 shows recombiant protein HBcAg-E7
49-57the purity of virus-like particle form (VLPs) and the HPLC gel-filtration analysis of form;
Fig. 5 shows recombiant protein HBcAg-E7
49-57the non-viral purity of sample particle form (non-VLPs) and the HPLC gel-filtration analysis of form;
Fig. 6 shows electron microscopic observation to recombiant protein HBcAg-E7
49-57form the form of VLPs;
Fig. 7 shows electron microscopic observation to recombiant protein HBcAg-E7
49-57form the form of non-VLPs;
Fig. 8 shows virus sample particle vaccines significantly suppress the growth (n=9/ group) of tumor after therapeutic strategies immune mouse;
Fig. 9 shows and analyzes through ELISPOT, and virus sample particle vaccines is to significantly improve the lymphocyte level (n=5/ group) of secretion of gamma-IFN after therapeutic strategies immune mouse;
Figure 10 shows the experimental arrangement of immunological memory experiment;
Figure 11 shows and analyzes through ELISPOT, and after virus sample particle vaccines third time immunity, 15 weeks mices still exist immunne response (n=4/ group);
Figure 12 still creates significant tumor inhibitory effect (n=10/ group) after showing immune 15 weeks of third time of virus sample particle vaccines immunity;
Figure 13 shows latter 1 week of immunological memory experimental tumor inoculation, analyzes, create the lymphocyte (n=4/ group) of high-caliber secretion of gamma-IFN after virus sample particle vaccines immune mouse through ELISPOT.
Detailed description of the invention
The present invention is described in detail, so that those of ordinary skill in the art can understand the present invention better by following examples.Following embodiment only for exemplary purposes, is not intended to limit scope of the present invention.Endeavour to ensure the accuracy of Values, but should consider there is some errors and deviation.
embodiment
embodiment 1: recombinant expression plasmid phBcAg-E7
49-57 structure
Coding E7
49-57oligonucleotide sequence (normal chain: 5 '-gatctCGTGCTCACTACAACATCGTTACCTTCggatccggtg-3 '; Minus strand: 5 '-aattcaccggatccGAAGGTAACGATGTTGTAGTGAGCACGa-3 ') synthesized by Sangon Biotech (Shanghai) Co., Ltd..In the system of 10 μ l, positive and negative oligonucleotide fragment mixes annealing renaturation with the concentration 1:1 of 0.1mM, and renaturation system is specially: each 2 μ l, 10 × PCRBuffer1 μ l, the water 5 μ l of positive and negative oligonucleotide.Degeneration 30 seconds under the condition of 95 DEG C, slowly until be cooled to annealing at room temperature renaturation, thus forms the double chain DNA fragment of coding for antigens peptide.The double chain DNA fragment formed builds up between pThioHisA-HBcAg carrier B amH I and EcoR I restriction enzyme site.Carrier pThioHisA-HBcAg, is built by this room, is by transformed HBcAg(1-149 aminoacid) gene clone is in pThioHisA expression vector (Fig. 1).Linked system is: E7
49-57dNA fragmentation 2.84 μ l, pThioHisA-HBcAg carrier 6.14 μ l, 10 × T4Buffer1.5 μ l, T4 ligase 1 μ l, water: 3.5 μ l, 16 DEG C of connections are spent the night.DNA is connected product conversion and enter bacillus coli DH 5 alpha competent cell, picking positive colony qualification of checking order.
embodiment 2: recombinant expression plasmid phBcAg-E7
49-57 abduction delivering
Recombinant plasmid transformed is entered bacillus coli DH 5 alpha competent cell, picking monoclonal carries out abduction delivering, concrete grammar is, positive colony is seeded in the LB culture medium having added ampicillin (100mg/mL), cultivating after 16 hours enters in the LB culture medium of new band ampicillin with the ratio of 1:5 switching bacterium liquid, when strain growth is to logarithmic (log) phase, adds IPTG(1mmol/L) carry out abduction delivering, controlling abduction delivering temperature is 37 DEG C, abduction delivering 4 hours (Fig. 2).
embodiment 3: recombiant protein phBcAg-E7
49-57 preparation and purification
Sample after being spent the night by abduction delivering centrifugal 10 minutes with room temperature 12000g, collect thalline, to carry out ultrasonic disruption after the resuspended thalline of PBS, broken condition is 15% peak power, works 5 seconds, stops 5 seconds, continues 10 minutes.Sample after fragmentation centrifugal 10 minutes with 12000g, to collect after supernatant and to carry out 40% ammonium sulfate precipitation precipitation at room temperature 30min.12,000rpm(~ 13000g), 20 DEG C of centrifugal 10min.Discard supernatant, precipitation with 20% ammonium sulfate washing, 12,000rpm(~ 13000g), 20 DEG C of centrifugal 10min, repeated washing three times, precipitates resuspended with 500 μ lPB, 12,000rpm(~ 13000g), 20 DEG C of centrifugal 15min, collection supernatant.
After SDS-PAGE analyzes, recombiant protein carries out purification through the sucrose density gradient centrifugation of 10% ~ 50%, and the sample after centrifugal successively samples from top to bottom, every layer of 1ml(Fig. 3).The recombiant protein of purification carries out HPLC analysis, and pillar is SRTSEC-1000, flow velocity 0.2ml/min, and mobile phase is PBS.According to appearance time qualification recombiant protein assembling assembly virus-like particle (Fig. 4) and unassembled one-tenth virus-like particle (non-VLPs) (Fig. 5).In addition, by the recombiant protein of purification after phosphotungstic acid negative staining, electron microscopic observation virus-like particle (VLPs) (Fig. 6) and non-viral sample granule (Fig. 7).
embodiment 4 mouse transplanting tumor model is set up and therapeutic strategies immunologic intervention
Right side of mice subcutaneous injection mixing BasementMembraneMatrix(BDBioscience) 1 × 10
5tC-1 cell, sets up mice HPV neoplasm transplantation.In curative test, mice is inoculated tumour cell first, mice tumors grew carries out vaccine immunity to during 2mm, mice is divided into five groups of i.e. PBS group (s.c.), NP group (s.c.), B4-VLPs group (s.c.), B4-noneVLPs groups (s.c.), often organize 9 mices, immunizing dose is 50 μ g, every only 100 μ l, immunity 3 times, every minor tick 1 week.Mouse tumor size was measured once every three days.(Fig. 8).After tumor inoculation 63 days, the lymphocyte of application ELISPOT test kit (reach section for) the specific secretion of gamma-IFN of detectable antigens, application E7
49-57peptide stimulates, and operating procedure is carried out to specifications.Remove mouse spleen with every porocyte number for 3 × 10
5individual paving to 96 porocyte culture plate, and apply the small peptide E7 of 5 μ g/ml
49-57carry out stimulated in vitro, 37 DEG C, 5%CO
216-20h(Fig. 9 is cultivated) in incubator.
embodiment 5hBcAg-E7
49-57 the persistence of the immunological memory that therapeutic vaccine causes
Mice is divided into four groups, immune programme for children is as Figure 10, be respectively: (1) vaccine group: 10 first immune virus sample particle vaccines of mice, immunity three times, every minor tick one week, immunizing dose is 50 μ g, immunne response situation is observed according to test set result, inoculated tumour cell TC-1 after last immune 15 weeks, gets 4 mouse spleens and carries out immunology detection (Figure 13) after one week, residue mice continues to observe tumor size (Figure 12).(2) vehicle group: first 10 mices inject NP as vehicle Control group, inject three times, every minor tick one week, injected dose is 50 μ g, immunne response situation is observed according to test set result, inoculated tumour cell TC-1 after last immune 15 weeks, gets 4 mouse spleens and carries out immunology detection after two weeks, residue mice continues to observe tumor size.Within after inoculated tumour cell 10 weeks, get residue mouse spleen, tumor carries out follow-up immunization detection; (3) PBS group: first 10 mices inject PBS as blank group, inject three times, every minor tick one week, immunne response situation is observed according to test set result, inoculated tumour cell TC-1 after last immune 15 weeks, get 4 mouse spleens after two weeks and carry out immunology detection, residue mice continues to observe tumor size.Within after inoculated tumour cell 10 weeks, get residue mouse spleen, tumor carries out follow-up immunization detection; (4) test set: 16 mouse immune B4 vaccines, immunity three times, every minor tick one week, immunizing dose is 50 μ g, get four test points after last immunity and observe mouse immune response situation, within 2 weeks, 5 weeks, 7 weeks and 15 weeks, detect after being respectively last immunity.The spleen that 4 mices are got in each detection carries out ELISPOT analysis, observes mouse immune response situation (Figure 11).
Claims (3)
1. a hepatitis B virus core antigen virus-like particle (HBcAg) can as the carrier of tumor therapeutic vaccine, it is characterized in that: tumor antigen presentation can be brought out the stronger cellullar immunologic response for institute's antigen-presenting behind HBcAg surface in body, induction body produces effective immunological memory, has significant inhibitory action to the tumor that human papilloma virus infection causes.
2. this hepatitis B virus core antigen virus-like particle is as the structure of therapeutic vaccine against cervical cancer carrier, and its method is: by encoding, the hepatitis B virus core antigen HBcAg blocked is cloned into pThioHisA carrier, then by E7
49-57positive and negative oligonucleotide sequence DNA fragmentation of being formed after annealing renaturation 78-79 of being inserted into HBcAg be between aminoacid, obtain recombiant plasmid pHBcAg-E7
49-57.
3. this hepatitis B virus core antigen virus-like particle is as the application of therapeutic vaccine against cervical cancer carrier, it is characterized in that: described is presented E7
49-57hepatitis B virus core antigen virus-like particle according to the inoculum concentration of 50 μ g, subcutaneous vaccination.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201510972747.8A CN105497886A (en) | 2015-12-23 | 2015-12-23 | Application of HBcAg (hepatitis B core antigen) virus-like particle serving as cancer therapeutic vaccine carrier |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201510972747.8A CN105497886A (en) | 2015-12-23 | 2015-12-23 | Application of HBcAg (hepatitis B core antigen) virus-like particle serving as cancer therapeutic vaccine carrier |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN105497886A true CN105497886A (en) | 2016-04-20 |
Family
ID=55706433
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201510972747.8A Pending CN105497886A (en) | 2015-12-23 | 2015-12-23 | Application of HBcAg (hepatitis B core antigen) virus-like particle serving as cancer therapeutic vaccine carrier |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN105497886A (en) |
Cited By (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN106620679A (en) * | 2016-12-27 | 2017-05-10 | 中国医学科学院医学生物学研究所 | Tumor vaccine with IL-33 (interleukin-33) used as therapeutic target |
| CN106806890A (en) * | 2016-12-28 | 2017-06-09 | 中国医学科学院医学生物学研究所 | Recombinant human VEGF polypeptide tumor vaccine |
| CN106905434A (en) * | 2017-02-28 | 2017-06-30 | 国药中生生物技术研究院有限公司 | A kind of recombination fusion protein comprising hoof bat hepatitis B core protein and its preparation method and application |
| CN112852852A (en) * | 2019-11-27 | 2021-05-28 | 中国医学科学院医学生物学研究所 | OX40 epitope recombinant virus-like particle and preparation method and application thereof |
| CN113150082A (en) * | 2020-12-29 | 2021-07-23 | 中国医学科学院医学生物学研究所 | Construction method of virus-like particle vaccine presenting peptide epitope of different regions of RBM of SARS-COV-2 |
Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1903363A (en) * | 2006-08-02 | 2007-01-31 | 中国农业大学 | Mosaic type virus-like particle DNA vaccine |
| CN101942013A (en) * | 2010-07-07 | 2011-01-12 | 中国人民解放军第三军医大学 | HLA-DR9 restrictive regulatory T cell epitope of Hepatitis B virus core antigen and e antigen and application thereof |
| CN102988976A (en) * | 2012-12-18 | 2013-03-27 | 中国人民解放军第三军医大学 | Hepatitis B virus core antigen-DNA (deoxyribonucleic acid) compound vaccine and preparation method thereof |
-
2015
- 2015-12-23 CN CN201510972747.8A patent/CN105497886A/en active Pending
Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1903363A (en) * | 2006-08-02 | 2007-01-31 | 中国农业大学 | Mosaic type virus-like particle DNA vaccine |
| CN101942013A (en) * | 2010-07-07 | 2011-01-12 | 中国人民解放军第三军医大学 | HLA-DR9 restrictive regulatory T cell epitope of Hepatitis B virus core antigen and e antigen and application thereof |
| CN102988976A (en) * | 2012-12-18 | 2013-03-27 | 中国人民解放军第三军医大学 | Hepatitis B virus core antigen-DNA (deoxyribonucleic acid) compound vaccine and preparation method thereof |
Non-Patent Citations (2)
| Title |
|---|
| QIONG LONG ET.AL: "Virus-like particles presenting interleukin-33 molecules immunization characteristics and potentials of blocking IL-33/st2 pathway in allergic airway inflammation", 《HUMAN VACCINES&IMMUNOTHERAPEUTICS》 * |
| 褚晓洁等: "基于HPV16E7蛋白CTLs抗原肽的病毒样颗粒治疗性疫苗的构建", 《中国生物工程杂志》 * |
Cited By (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN106620679A (en) * | 2016-12-27 | 2017-05-10 | 中国医学科学院医学生物学研究所 | Tumor vaccine with IL-33 (interleukin-33) used as therapeutic target |
| CN106806890A (en) * | 2016-12-28 | 2017-06-09 | 中国医学科学院医学生物学研究所 | Recombinant human VEGF polypeptide tumor vaccine |
| CN106905434A (en) * | 2017-02-28 | 2017-06-30 | 国药中生生物技术研究院有限公司 | A kind of recombination fusion protein comprising hoof bat hepatitis B core protein and its preparation method and application |
| CN106905434B (en) * | 2017-02-28 | 2021-01-26 | 国药中生生物技术研究院有限公司 | Recombinant fusion protein containing hepialus hepatitis virus core protein and preparation method and application thereof |
| CN112852852A (en) * | 2019-11-27 | 2021-05-28 | 中国医学科学院医学生物学研究所 | OX40 epitope recombinant virus-like particle and preparation method and application thereof |
| CN112852852B (en) * | 2019-11-27 | 2023-07-25 | 中国医学科学院医学生物学研究所 | OX40 epitope recombinant virus-like particle and preparation method and application thereof |
| CN113150082A (en) * | 2020-12-29 | 2021-07-23 | 中国医学科学院医学生物学研究所 | Construction method of virus-like particle vaccine presenting peptide epitope of different regions of RBM of SARS-COV-2 |
| CN113150082B (en) * | 2020-12-29 | 2022-11-08 | 中国医学科学院医学生物学研究所 | Method for constructing virus-like particle vaccine presenting peptide epitopes in different regions of RBM of SARS-COV-2 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| Ellis | New technologies for making vaccines | |
| Massa et al. | Anti-cancer activity of plant-produced HPV16 E7 vaccine | |
| AU2012210612B2 (en) | CyaA-carried polypeptide(s) and use to induce both therapeutic and prophylactic immune responses | |
| CN105497886A (en) | Application of HBcAg (hepatitis B core antigen) virus-like particle serving as cancer therapeutic vaccine carrier | |
| US20200246443A1 (en) | Therapeutic cancer vaccine targeted to haah (aspartyl-[asparaginyl]-beta-hydroxylase) | |
| Seo et al. | Optimal induction of HPV DNA vaccine-induced CD8+ T cell responses and therapeutic antitumor effect by antigen engineering and electroporation | |
| Kang et al. | Enhancement of protein vaccine potency by in vivo electroporation mediated intramuscular injection | |
| CN113633764A (en) | Novel corona DNA vaccine containing adjuvant | |
| CN106632694A (en) | Recombinant protein and medicine composition and application thereof | |
| Partidos et al. | The bare skin and the nose as non-invasive routes for administering peptide vaccines | |
| CN102286104B (en) | Gene for encoding HPV (human papilloma virus) 6-type L2N120E7E6 fusion protein, expression vectors, method, bacteria strain and application | |
| Daemi et al. | Different domains of glycoprotein 96 influence HPV16 E7 DNA vaccine potency via electroporation mediated delivery in tumor mice model | |
| CN111548395A (en) | Bivalent multi-epitope recombinant virus-like particle of foot-and-mouth disease virus and application thereof | |
| CN103864936A (en) | HPV18 type L2NE7E6 fusion protein gene, and expression vector, preparation method, strain and use thereof | |
| Garmory et al. | DNA vaccines for biodefence | |
| Mahdy et al. | Development of a recombinant vaccine against foot and mouth disease utilizing mutant attenuated Listeria ivanovii strain as a live vector | |
| Kumar et al. | DNA vaccine: a modern biotechnological approach towards human welfare and clinical trials | |
| JP2019142947A (en) | Mono- or multivalent botulinum neurotoxin vaccine using heavy chain from serotypes of clostridium botulinum | |
| WO2022105880A1 (en) | Fusion gene, recombinant novel coronavirus high-efficiency immune dna vaccine, construction method therefor and use thereof | |
| CN103087198B (en) | MRSA (Methicillin Resistant Staphylococcus Aureus) vaccine recombinant protein antigen I1C and preparation method and application thereof | |
| KR20180068937A (en) | Soluble Multi-Epitope Antigen of Foot-and-Mouth Disease Virus and Uses Thereof | |
| KR101975895B1 (en) | Soluble Multi-Epitope Antigen of Foot-and-Mouth Disease Virus and Uses Thereof | |
| CN102000330B (en) | Nucleic acid vaccine adjuvant and construction method thereof | |
| CN104402974A (en) | Polypeptide with mucosal immunity adjuvant activity, and application of polypeptide in preparation of mucosal immunity adjuvant | |
| FI3737397T3 (en) | Cancer vaccines targeting prame and uses thereof |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| C10 | Entry into substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| WD01 | Invention patent application deemed withdrawn after publication | ||
| WD01 | Invention patent application deemed withdrawn after publication |
Application publication date: 20160420 |