WO2021042947A1 - Conception et utilisation de vaccin à adn minicercle - Google Patents

Conception et utilisation de vaccin à adn minicercle Download PDF

Info

Publication number
WO2021042947A1
WO2021042947A1 PCT/CN2020/108419 CN2020108419W WO2021042947A1 WO 2021042947 A1 WO2021042947 A1 WO 2021042947A1 CN 2020108419 W CN2020108419 W CN 2020108419W WO 2021042947 A1 WO2021042947 A1 WO 2021042947A1
Authority
WO
WIPO (PCT)
Prior art keywords
antigen
hpv
vector
protein
seq
Prior art date
Application number
PCT/CN2020/108419
Other languages
English (en)
Chinese (zh)
Inventor
谌平
谢亦武
陈志英
Original Assignee
深圳新诺微环生物科技有限公司
Priority date (The priority date 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 date listed.)
Filing date
Publication date
Application filed by 深圳新诺微环生物科技有限公司 filed Critical 深圳新诺微环生物科技有限公司
Publication of WO2021042947A1 publication Critical patent/WO2021042947A1/fr

Links

Images

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
    • A61K39/02—Bacterial antigens
    • A61K39/07—Bacillus
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
    • A61P31/04—Antibacterial agents
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00—Antineoplastic agents
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • C07K14/005—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from viruses
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • C07K14/195—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from bacteria
    • C07K14/32—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from bacteria from Bacillus (G)
    • 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
    • A61K2039/53—DNA (RNA) vaccination
    • 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
    • A61K2039/555—Medicinal preparations containing antigens or antibodies characterised by a specific combination antigen/adjuvant
    • A61K2039/55511—Organic adjuvants
    • 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
    • A61K2039/57—Medicinal preparations containing antigens or antibodies characterised by the type of response, e.g. Th1, Th2
    • A61K2039/575—Medicinal preparations containing antigens or antibodies characterised by the type of response, e.g. Th1, Th2 humoral response
    • 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
    • C12N2710/20022—New viral proteins or individual genes, new structural or functional aspects of known viral proteins or genes

Definitions

  • the invention belongs to the field of biomedicine, and specifically relates to a minicircle (MC) DNA carrier, and more specifically to the design and application of a minicircle (MC) DNA vaccine.
  • Vaccines refer to biological agents that can stimulate the body to effectively produce acquired immunity against specific diseases, and are generally composed of inactivated or attenuated pathogens, toxins, pathogenic proteins or peptides.
  • the technology closest to the present invention is a plasmid-based DNA vaccine.
  • plasmid-based DNA vaccine With the development of immunology, research has found that direct introduction of recombinant plasmids carrying antigen-encoding genes into humans or animals, using host cells to synthesize antigen proteins, can induce the body to produce antigen-specific humoral and cellular immune responses, thereby preventing or treating diseases .
  • DNA vaccines have distinct advantages, and there are more and more preclinical and clinical research reports. But so far, there is no human DNA vaccine product approved for marketing. Compared with traditional vaccines, DNA vaccines have low immunogenicity and are difficult to provoke a sufficiently effective immune response. In addition, plasmids carry resistance screening genes, and the potential safety hazards such as the spread of resistance genes caused by this cannot be ignored.
  • DNA itself has no or very low immunogenicity.
  • the source of DNA vaccine immunogenicity essentially refers to the encoded antigen protein.
  • the low transfection efficiency of plasmids in vivo and the limited antigen protein produced in the host body are the fundamental reasons for the low immunogenicity of DNA vaccines. Because the minicircle DNA removes the prokaryotic backbone DNA components in the plasmid, the vector is greatly reduced, which is conducive to in vivo transfection. More importantly, due to the removal of the "transgene silencing effect", the expression of minicircle DNA in vivo is much higher than that of plasmids.
  • the invention utilizes the Minicircle (MC) DNA vector to encode the antigen gene, which can mediate the high-efficiency expression of the antigen protein in the body, enhance the immunogenicity of the DNA vaccine, and can also avoid the safety problem caused by the resistance gene.
  • MC Minicircle
  • the present invention relates to a minicircle (MC) DNA carrier, and the use of the minicircle DNA carrier to express antigens or antigen fragments in the body to stimulate the body to produce specific humoral immunity (antibody) and cellular immune responses, thereby preventing or treating infectious diseases and Related cancers.
  • MC minicircle
  • the present invention provides a recombinant gene vector expressing an antigen or an antigen fragment, wherein the recombinant gene vector contains the coding gene of the antigen or antigen fragment.
  • the antigen is selected from pathogen specific antigens.
  • the recombinant gene vector is selected from a non-viral vector or a viral vector.
  • the non-viral vector is selected from a standard plasmid or other circular expression cassettes, or the viral vector is selected from a retroviral vector, a lentiviral vector, an adenovirus vector and an adeno-associated virus vector.
  • the pathogenic microorganism-specific antigen or antigen fragment is selected from the group consisting of Bacillus anthracis protective antigen (Protective Antigen, PA), human papillomavirus (HPV) early protein (E6 or E7) antigen, HPV late protein (L1 or L2) Antigen, the non-viral vector is selected from a minicircle DNA vector, or the viral vector is selected from an adeno-associated virus vector.
  • Bacillus anthracis protective antigen Protective Antigen, PA
  • HPV human papillomavirus
  • E6 or E7 antigen
  • HPV late protein L1 or L2
  • the non-viral vector is selected from a minicircle DNA vector
  • the viral vector is selected from an adeno-associated virus vector.
  • the amino acid sequence of the Bacillus anthracis PA antigen is shown in SEQ ID NO: 2; the HPV early protein antigen is selected from the HPV E6/E7 chimeric protein antigen, and its amino acid sequence is shown in SEQ ID NO: 3.
  • the HPV late protein antigen is selected from (1) HPV L1 protein antigen, and its amino acid sequence is shown in SEQ ID NO: 4, (2) HPV L2 protein antigen, and its amino acid sequence is shown in SEQ ID NO: 5.
  • the Bacillus anthracis PA antigen has an amino acid sequence that is at least 90%, 95%, 98% or 99% homologous to the sequence shown in SEQ ID NO: 2, and has the same amino acid sequence as the previous Bacillus anthracis PA antigen.
  • the HPV E6/E7 chimeric protein antigen has an amino acid sequence that is at least 90%, 95%, 98% or 99% homologous to the sequence shown in SEQ ID NO: 3, and has an amino acid sequence that is similar to the previous HPV E6/E7 Synthetic protein antigen;
  • the HPV L1 protein antigen has an amino acid sequence that is at least 90%, 95%, 98%, or 99% homologous to the sequence shown in SEQ ID NO: 4, and has the same function as the previous HPV L1 protein antigen The same function;
  • the HPV L2 protein antigen has an amino acid sequence with at least 90%, 95%, 98% or 99% homology with the sequence shown in SEQ ID NO: 5, and has the same function as the previous HPV L2 protein antigen
  • the HPV L1/L2 chimeric protein antigen has an amino acid sequence that is at least 90%, 95%, 98%, or 99% homologous to the sequence shown in SEQ ID NO: 6, and has an amino acid sequence that is chimeric with the previous
  • the nucleotide sequence of the Bacillus anthracis PA antigen-encoding gene is shown in SEQ ID NO: 7; the nucleotide sequence of the HPV E6/E7 chimeric protein antigen-encoding gene is shown in SEQ ID NO: 8
  • the nucleotide sequence of the gene encoding the HPV L1 protein antigen is shown in SEQ ID NO: 9; the nucleotide sequence of the HPV L2 protein antigen encoding gene is shown in SEQ ID NO: 10; the HPV The nucleotide sequence of the gene encoding the L1/L2 chimeric protein antigen is shown in SEQ ID NO: 11.
  • the Bacillus anthracis PA antigen-encoding gene has a nucleotide sequence that is at least 90%, 95%, 98%, or 99% homologous to the sequence shown in SEQ ID NO: 7, and encodes the resulting Bacillus anthracis
  • the PA antigen has the same function as the previous Bacillus anthracis PA antigen
  • the HPV E6/E7 chimeric protein antigen coding gene has at least 90%, 95%, 98% or 99% homology with the sequence shown in SEQ ID NO: 8
  • the encoded HPV E6/E7 chimeric protein antigen has the same function as the previous HPV E6/E7 chimeric protein antigen
  • the HPV L1 protein antigen encoding gene has the same function as SEQ ID NO: 9
  • This application also provides a method for preparing the aforementioned recombinant gene vector, the specific steps include:
  • the recombinant gene vector contains the gene encoding the antigen.
  • the antigen is selected from pathogen specific antigens or antigen fragments.
  • the recombinant gene vector is selected from a non-viral vector or a viral vector.
  • the non-viral vector is selected from a standard plasmid or other circular expression cassettes, or the viral vector is selected from a retroviral vector, a lentiviral vector, an adenovirus vector and an adeno-associated virus vector.
  • the pathogenic microorganism-specific antigen is selected from the group consisting of Bacillus anthracis PA antigen, HPV early protein (E6 or E7) antigen, HPV late protein (L1 or L2) antigen, and the non-viral vector is selected from minicircle DNA vector, Or the viral vector is selected from adeno-associated viral vectors.
  • the HPV early protein antigen is selected from HPV E6/E7 chimeric protein antigen; the HPV late protein antigen is selected from (1) HPV L1 protein antigen, (2) HPV L2 protein antigen or (3) HPV L1/L2 chimeric protein antigen. Binding protein antigen.
  • the application also provides a host cell, which contains the aforementioned recombinant gene vector.
  • the host cell includes a bacterial cell, a yeast cell, an insect cell, or a mammalian cell.
  • the application also provides a pharmaceutical composition, which comprises the aforementioned recombinant gene carrier and a pharmaceutically acceptable carrier.
  • the pharmaceutical composition can be made into a pharmaceutical preparation according to conventional methods. During the preparation process, it is preferable to mix or dilute the recombinant gene carrier with a pharmaceutically acceptable carrier.
  • a pharmaceutically acceptable carrier When the carrier serves as a diluent, it can be solid, semi-solid or liquid.
  • the preparation is selected from the form of tablets, pills, powders, capsules, suspensions, emulsions, solutions, aerosols, injection solutions and the like.
  • Suitable carriers, excipients or diluents include water, lactose, glucose, sucrose, sorbitol, mannitol, calcium silicate, cellulose, polyvinylpyrrolidone, methyl hydroxybenzoate, propyl hydroxybenzoate, talc , Magnesium stearate and mineral oil.
  • the formulation may also include fillers, anticoagulants, lubricants, moisturizers, flavoring agents, emulsifiers, preservatives, and the like.
  • the application also provides the use of the recombinant gene vector, the host cell, or the pharmaceutical composition in the preparation of a medicine for the treatment of diseases.
  • the disease is selected from infectious diseases or cancer.
  • infectious disease is selected from Bacillus anthracis infection or HPV infection
  • cancer is selected from cancers related to pathogenic microorganisms, such as cervical cancer, liver cancer, and nasopharyngeal cancer.
  • the positive effects of the present invention include: the use of the minicircle DNA carrier can mediate the high-efficiency expression of the antigen protein in the body, enhance the immunogenicity of the DNA vaccine, and at the same time can avoid the safety problem caused by the resistance gene.
  • Figure 1 Map of Bacillus anthracis PA antigen minicircle DNA vector.
  • Figure 2 HPV E6/E7 chimeric protein antigen minicircle DNA vector map.
  • Figure 3 HPV L1/L2 chimeric protein antigen minicircle DNA vector map.
  • FIG. 4 Western Blot detects the expression level of the Bacillus anthracis PA antigen minicircle DNA vector (MC.PA), which is significantly higher than the expression level of the plasmid (PL.PA).
  • MC.PA Bacillus anthracis PA antigen minicircle DNA vector
  • PL.PA plasmid
  • Figure 5 Bacillus anthracis PA antigen minicircle DNA carrier vaccine immunized mice, induced the mice to produce PA antigen-specific IgG antibodies, the level is equivalent to protein vaccine + aluminum adjuvant.
  • the target gene is selected from Bacillus anthracis PA, HPV E6/E7 chimeric protein, HPV L1 protein, HPV L2 protein or HPV L1/L2 chimeric protein and other coding gene sequences (such as SEQ ID NO : 7-11).
  • the target gene fragment is subcloned between the attB and attP sites of the minicircle DNA empty vector to construct the minicircle DNA parent plasmid.
  • the minicircle DNA parent plasmid contains attB and attP recombination sites, 32 tandem repeated I-SceI restriction sites (I-SceI*32), kana resistance gene, and SV40 DNA nuclear targeting sequence (DNA nuclear targeting sequence, DTS) ), CMV promoter/enhancer, chimeric intron, target gene, bovine growth factor (bovine growth hormone, bGH) poly A signal.
  • the minicircle DNA parent plasmid is transformed into genetic engineering E coli bacteria ZYCY10P3S2T (Nature Biotechnology 2010, 28:1287-9).
  • ZYCY10P3S2T expresses ⁇ C31 recombinase and an endonuclease that recognizes the I-SceI site.
  • the minicircle DNA parent plasmid undergoes DNA recombination at the attB/attP recombination site to form two small circular DNA molecules: i) Minicircle DNA (only containing the target gene expression box and 36-bp AttR site); ii) a small circle composed of plasmid backbone DNA (containing I-SceI restriction site).
  • minicircle formed by the plasmid backbone DNA and the unrecombined residual minicircle DNA parent plasmid are linearized under the action of I-SceI endonuclease, and then degraded by DNase, leaving only the minicircle DNA in the ZYCY10P3S2T bacteria.
  • Electrophoresis After adding an appropriate amount of loading buffer to the protein sample, heat it in boiling water for 3-5 minutes to denature the protein. After cooling, add the sample to the sample hole of the SDS-PAGE gel and electrophoresis at 80-100V for 1 hour.
  • Transfer membrane Use a wet transfer membrane device (Bio-Rad, USA) to transfer the membrane at 300 mA for 1 hour to transfer the protein from the SDS-PAGE gel to the PVDF membrane.
  • Example 4 Bacillus anthracis PA antigen minicircle DNA (MC.PA) mouse immunization experiment
  • mice were immunized according to the grouping scheme, blood was collected regularly every 4 weeks (day 28, 56 and 84), and the serum anthrax PA specific antibody level of the mice was detected by ELISA.
  • FIG. 5 Mouse immunization results show: intramuscular injection of MC.PA microcircle DNA (+EP) can induce the body to produce a large number of antibodies specific to Bacillus anthracis PA.
  • the antibody level is equivalent to that of protein vaccine (+ aluminum hydroxide adjuvant), and the type of antibody Mainly IgG1 and IgG2a subtypes.

Landscapes

  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Organic Chemistry (AREA)
  • General Health & Medical Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Veterinary Medicine (AREA)
  • Public Health (AREA)
  • Animal Behavior & Ethology (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Genetics & Genomics (AREA)
  • Biophysics (AREA)
  • Gastroenterology & Hepatology (AREA)
  • Biochemistry (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Chemical & Material Sciences (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Molecular Biology (AREA)
  • Oncology (AREA)
  • Communicable Diseases (AREA)
  • Virology (AREA)
  • Immunology (AREA)
  • Microbiology (AREA)
  • Mycology (AREA)
  • Epidemiology (AREA)
  • Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
  • Peptides Or Proteins (AREA)
  • Micro-Organisms Or Cultivation Processes Thereof (AREA)

Abstract

L'invention concerne la conception et l'utilisation d'un vaccin à ADN minicercle. Spécifiquement, l'invention concerne un vecteur d'ADN minicercle pour exprimer des antigènes spécifiques ou des fragments d'antigène de micro-organismes pathogènes in vivo. Le vecteur d'ADN minicercle peut médier des protéines d'antigène à exprimer efficacement in vivo, l'immunogénicité de vaccins à ADN est améliorée et, dans le même temps, le problème de sécurité provoqué par des gènes de résistance peut être évité. Le vecteur d'ADN minicercle peut être utilisé pour prévenir et/ou traiter des maladies infectieuses communes ainsi que des cancers associés et présente les avantages d'une expression d'antigène plus forte et d'une sécurité plus élevée.
PCT/CN2020/108419 2019-09-03 2020-08-11 Conception et utilisation de vaccin à adn minicercle WO2021042947A1 (fr)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
CN201910825875.8 2019-09-03
CN201910825875.8A CN110564751A (zh) 2019-09-03 2019-09-03 微环dna疫苗设计及应用

Publications (1)

Publication Number Publication Date
WO2021042947A1 true WO2021042947A1 (fr) 2021-03-11

Family

ID=68777446

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/CN2020/108419 WO2021042947A1 (fr) 2019-09-03 2020-08-11 Conception et utilisation de vaccin à adn minicercle

Country Status (2)

Country Link
CN (1) CN110564751A (fr)
WO (1) WO2021042947A1 (fr)

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US11324839B2 (en) 2019-09-18 2022-05-10 Intergalactic Therapeutics, Inc. b Synthetic DNA vectors and methods of use

Families Citing this family (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN110564751A (zh) * 2019-09-03 2019-12-13 深圳新诺微环生物科技有限公司 微环dna疫苗设计及应用
WO2024140767A1 (fr) * 2022-12-29 2024-07-04 仁景(苏州)生物科技有限公司 Molécule polynucléotidique pour la prévention ou le traitement de maladies liées à une infection par le vph

Citations (8)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN104587490A (zh) * 2014-09-25 2015-05-06 中国人民解放军第四五八医院 治疗性hbv微环dna疫苗及其制备方法
US20180094050A1 (en) * 2016-10-05 2018-04-05 Duke University Vaccines against her3 antigens and methods of using the same
US20180092989A1 (en) * 2016-10-05 2018-04-05 Duke University Mitochondrial antiviral signaling (mavs) protein compositions and methods of using the same
CN108424925A (zh) * 2018-03-07 2018-08-21 江苏润洁生物科技有限公司 一种治疗性hpv核酸疫苗
CN108424926A (zh) * 2018-03-07 2018-08-21 江苏润洁生物科技有限公司 一种用于预防hpv感染的核酸疫苗
CN108949791A (zh) * 2017-10-26 2018-12-07 深圳新诺微环生物科技有限公司 微环dna表达抗hpv治疗性工程抗体及其应用
CN109536521A (zh) * 2018-11-26 2019-03-29 吉林农业大学 一种微环dna及其制备方法与应用
CN110564751A (zh) * 2019-09-03 2019-12-13 深圳新诺微环生物科技有限公司 微环dna疫苗设计及应用

Family Cites Families (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN104342453A (zh) * 2013-08-06 2015-02-11 深圳先进技术研究院 含基因工程抗体基因表达盒的微环dna重组母质粒、含该表达盒的微环dna及应用
CN104561069A (zh) * 2013-10-23 2015-04-29 深圳先进技术研究院 含重组嵌合抗原受体基因表达盒的微环dna重组母质粒、含该表达盒的微环dna及应用
CN108728463A (zh) * 2017-04-14 2018-11-02 深圳新诺微环生物科技有限公司 一种表达IgG抗体的微环DNA载体及其制备方法和应用
CN108410823B (zh) * 2018-03-26 2019-11-01 安徽中盛溯源生物科技有限公司 一种微环游离型载体高效重编程血液细胞生成iPSC的方法

Patent Citations (8)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN104587490A (zh) * 2014-09-25 2015-05-06 中国人民解放军第四五八医院 治疗性hbv微环dna疫苗及其制备方法
US20180094050A1 (en) * 2016-10-05 2018-04-05 Duke University Vaccines against her3 antigens and methods of using the same
US20180092989A1 (en) * 2016-10-05 2018-04-05 Duke University Mitochondrial antiviral signaling (mavs) protein compositions and methods of using the same
CN108949791A (zh) * 2017-10-26 2018-12-07 深圳新诺微环生物科技有限公司 微环dna表达抗hpv治疗性工程抗体及其应用
CN108424925A (zh) * 2018-03-07 2018-08-21 江苏润洁生物科技有限公司 一种治疗性hpv核酸疫苗
CN108424926A (zh) * 2018-03-07 2018-08-21 江苏润洁生物科技有限公司 一种用于预防hpv感染的核酸疫苗
CN109536521A (zh) * 2018-11-26 2019-03-29 吉林农业大学 一种微环dna及其制备方法与应用
CN110564751A (zh) * 2019-09-03 2019-12-13 深圳新诺微环生物科技有限公司 微环dna疫苗设计及应用

Non-Patent Citations (2)

* Cited by examiner, † Cited by third party
Title
HU CHUN-SHENG , ZHANG TONG ,ZHANG QING-LIN: "Research Progress of Minicircle DNA", LETTERS IN BIOTECHNOLOGY, vol. 22, no. 1, 30 January 2011 (2011-01-30), pages 104 - 107+112, XP008182107, ISSN: 1009-0002, DOI: 10.3969/j.issn.1009-0002.2011.01.024 *
RAO GUI-RONG , ZHANG HUAN-JING ,HUANG BIN ,CHEN GUANG-MING ,WANG HONG-MIN ,YANG FU-QIANG: "Construction, Identification and Pharmacodynamics Research on a Minicircle DNA Recombinant Plasmid of HBV", INFECTIOUS DISEASE INFORMATION, vol. 28, no. 2, 30 April 2015 (2015-04-30), pages 88 - 91+98, XP055788405, ISSN: 1007-8134 *

Cited By (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US11324839B2 (en) 2019-09-18 2022-05-10 Intergalactic Therapeutics, Inc. b Synthetic DNA vectors and methods of use
US11602569B2 (en) 2019-09-18 2023-03-14 Intergalactic Therapeutics, Inc. Synthetic DNA vectors and methods of use
US11684680B2 (en) 2019-09-18 2023-06-27 Intergalactic Therapeutics, Inc. Synthetic DNA vectors and methods of use
US11766490B2 (en) 2019-09-18 2023-09-26 Intergalactic Therapeutics, Inc. Synthetic DNA vectors and methods of use

Also Published As

Publication number Publication date
CN110564751A (zh) 2019-12-13

Similar Documents

Publication Publication Date Title
CN116143938B (zh) 一种covid-19亚单位疫苗及其制备方法与应用
WO2021042947A1 (fr) Conception et utilisation de vaccin à adn minicercle
CN111662389A (zh) 一种SARS-CoV-2的融合蛋白及其疫苗组合物
CN111778264B (zh) 基于新型腺病毒载体Sad23L和/或Ad49L的新型冠状病毒肺炎疫苗
CN109182380B (zh) 杆状病毒表达的猪瘟e2亚单位疫苗的制备方法及应用
CN112011521A (zh) 一种重组新城疫病毒载体新型冠状病毒疫苗候选株及其构建方法和应用
CN113201507A (zh) 一种重组的伪狂犬病病毒及其疫苗组合物
CN111548395A (zh) 一种口蹄疫病毒二价多表位重组病毒样颗粒及其应用
CN110951699A (zh) 表达犬瘟热病毒结构蛋白的重组狂犬病病毒及其应用
KR101919002B1 (ko) 구제역 바이러스의 가용성 다가 항원단백질 및 이의 용도
CN113528549B (zh) 编码新型冠状病毒b.1.351突变株抗原的dna分子、dna疫苗及应用
WO2023142647A1 (fr) Vaccin thérapeutique à base d'acide nucléique d'un nouveau type contre le virus du papillome humain (vhp)
CN116024237A (zh) 一种用于预防裂谷热的mRNA疫苗及其制备方法
CN114437236B (zh) 一种重组非洲猪瘟病毒多表位融合蛋白、制备及其应用
CN115094088A (zh) 一种pSFV-flagX-CMV复制子质粒、制备方法和鸡尾酒混合疫苗
CN109568574B (zh) sPD1蛋白和/或sPD1基因作为免疫佐剂的应用
KR101845571B1 (ko) 전통적 돼지열에 대한 마커 백신
CN111514287A (zh) 甲型流感通用型dna疫苗及其制备方法和应用
CN104651316A (zh) 一种重组猪圆环病毒病毒样颗粒及其制备方法
CN116904489B (zh) 一种鸭坦布苏病毒核酸疫苗及应用
CN114573667B (zh) SARS-CoV-2病毒B.1.1.529突变株DNA疫苗及应用
CN114807225B (zh) 一种抗羊口疮和绵羊痘的重组dna疫苗及其重组质粒
CN109207504B (zh) 一种有效免疫ib与nd的唾液乳酸杆菌的制备方法
CN118436773A (zh) 基于BCG载体的SARS-CoV-2多表位决定簇重组活疫苗及制备方法
CN116063406A (zh) 一种猫传染性鼻气管炎疫苗及其制备方法和应用

Legal Events

Date Code Title Description
121 Ep: the epo has been informed by wipo that ep was designated in this application

Ref document number: 20861188

Country of ref document: EP

Kind code of ref document: A1

NENP Non-entry into the national phase

Ref country code: DE

122 Ep: pct application non-entry in european phase

Ref document number: 20861188

Country of ref document: EP

Kind code of ref document: A1

122 Ep: pct application non-entry in european phase

Ref document number: 20861188

Country of ref document: EP

Kind code of ref document: A1