[go: up one dir, main page]

CN1114690C - 乳头瘤假病毒及其制备方法 - Google Patents

乳头瘤假病毒及其制备方法 Download PDF

Info

Publication number
CN1114690C
CN1114690C CN01118003A CN01118003A CN1114690C CN 1114690 C CN1114690 C CN 1114690C CN 01118003 A CN01118003 A CN 01118003A CN 01118003 A CN01118003 A CN 01118003A CN 1114690 C CN1114690 C CN 1114690C
Authority
CN
China
Prior art keywords
pseudovirus
papilloma
plasmid
virus
preparation
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.)
Expired - Fee Related
Application number
CN01118003A
Other languages
English (en)
Other versions
CN1333338A (zh
Inventor
乔良
石伟
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Individual
Original Assignee
Individual
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
Priority to CN01118003A priority Critical patent/CN1114690C/zh
Application filed by Individual filed Critical Individual
Priority to JP2001321828A priority patent/JP4511090B2/ja
Publication of CN1333338A publication Critical patent/CN1333338A/zh
Priority to PCT/CN2002/000187 priority patent/WO2002092796A1/zh
Priority to US10/294,087 priority patent/US6878541B2/en
Application granted granted Critical
Publication of CN1114690C publication Critical patent/CN1114690C/zh
Priority to US11/060,034 priority patent/US7205126B2/en
Priority to US11/784,626 priority patent/US8129144B2/en
Priority to JP2007124042A priority patent/JP4472724B2/ja
Priority to US13/413,386 priority patent/US20120164173A1/en
Anticipated expiration legal-status Critical
Expired - Fee Related legal-status Critical Current

Links

Classifications

    • 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
    • C12N7/00—Viruses; Bacteriophages; Compositions thereof; Preparation or purification thereof
    • 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
    • A61P31/12—Antivirals
    • 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
    • A61P31/12—Antivirals
    • A61P31/14—Antivirals for RNA viruses
    • A61P31/18—Antivirals for RNA viruses for HIV
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00—Antineoplastic agents
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00—Antineoplastic agents
    • A61P35/02—Antineoplastic agents specific for leukemia
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P9/00—Drugs for disorders of the cardiovascular system
    • 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
    • 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
    • C12N2710/20023—Virus like particles [VLP]
    • 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
    • C12N2710/20061—Methods of inactivation or attenuation

Landscapes

  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Medicinal Chemistry (AREA)
  • General Health & Medical Sciences (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Engineering & Computer Science (AREA)
  • Pharmacology & Pharmacy (AREA)
  • General Chemical & Material Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Virology (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Genetics & Genomics (AREA)
  • Zoology (AREA)
  • Wood Science & Technology (AREA)
  • Oncology (AREA)
  • General Engineering & Computer Science (AREA)
  • Communicable Diseases (AREA)
  • Biochemistry (AREA)
  • Microbiology (AREA)
  • Immunology (AREA)
  • Biomedical Technology (AREA)
  • Biotechnology (AREA)
  • Hematology (AREA)
  • Heart & Thoracic Surgery (AREA)
  • AIDS & HIV (AREA)
  • Molecular Biology (AREA)
  • Cardiology (AREA)
  • Tropical Medicine & Parasitology (AREA)
  • Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Micro-Organisms Or Cultivation Processes Thereof (AREA)
  • Medicines Containing Material From Animals Or Micro-Organisms (AREA)

Abstract

本发明涉及一种能通过口服途径产生免疫反应的乳头瘤假病毒及其制备方法。其特点，是将人乳头瘤病毒样颗粒(HPV-VLP)或牛乳头瘤病毒样颗粒(BPV-VLP)，解离，掺入质粒(plasmids或DNA疫苗)，从新组合成人或牛乳头瘤假病毒，通过口服送入人体的粘膜和系统性淋巴组织，激活人体的免疫反应，起到防病治病的作用，此假病毒可以诱导出比基因疫苗更强的免疫反应。之外，此假病毒可以将基因送到体内淋巴组织，可以用于基因治疗。

Description

乳头瘤假病毒及其制备方法
本发明涉及一种能通过口服途径产生免疫反应的乳头瘤假病毒及其制备方法。此假病毒可以用于疫苗来预防和治疗粘膜致病菌感染或粘膜肿瘤，此假病毒也可用于基因治疗。
我们都知道病原微生物和人体免疫机能缺陷是导致许多疾病的根源，人体经常遭受病原微生物的侵袭及人体内部暗藏的肿瘤的破坏。因此，人体也需要一种机体抵抗力或免疫力来抵抗病原微生物的入侵感染和机体内部的病变。目前临床使用的疫苗是通过皮下或肌肉注射，从而产生特异的免疫反应，导致对这种疾病的抵抗能力，使以后不再得这种病。但是，这些疫苗往往是皮下或肌肉注入人体后，只能产生系统性免疫反应，而不能产生粘膜免疫反应。这样的疫苗往往不能预防和治疗粘膜传染的致病菌。但是，许多致病菌是由粘膜传染的，比如：艾兹病。
本发明的目的就是研究出一种不会致病的类似病毒的假病毒，将用于治疗和预防疾病的基因或DNA疫苗注入病毒外壳内，通过口服的途径送入人体的粘膜和系统性淋巴组织，激活人体的免疫反应，起到防病治病的作用。
本发明所说的乳头瘤假病毒是将人乳头瘤病毒样颗粒(HPV-VLP)或牛乳头瘤病毒样颗粒(BPV-VLP)，解离，掺入质粒(plasmids)，从新组合成人或牛乳头瘤假病毒。正常病毒是由一个外壳和壳内的DNA构成，而发明所说的这个乳头瘤假病毒只有一个病毒的外壳，而无壳内的病毒的DNA。如果将DNA疫苗放入这个病毒外壳内，就可以通过口服送入人体内。本发明所述的DNA疫苗只是一段DNA片段，不是病毒的DNA，若把这个DNA片段皮下或肌肉注射人体内，就可以诱导系统免疫反应。含有DNA疫苗的病毒外壳就是本发明所述的假病毒。此假病毒的制备方法如下：
(1)将乳头瘤病毒样颗粒与解离缓冲液混合，体积混合比为1∶1，培养60min，室温；解离缓冲液：乙二醇二(β-氨基乙醚)四乙酸(EGTA)20mM，二硫苏糖醇(DTT)40mM，氯化钠(NaCl)300mM，三(羟甲基)氨基甲烷盐酸盐(Tris-HCl)(PH8.0)100mM；
(2)加入1/10体积的质粒：0.5-1μg/μl的质粒；
(3)逐渐加入终止缓冲液，终止缓冲液为：氯化钙(CaCl2)25mM，二甲基亚砜(DMSO)20％体积百分比；
(4)混合好的混合液放在4℃过夜。
此假病毒不致病，可用于基因治疗，即将所要表达的基因插入质粒，装入病毒样颗粒，此假病毒即可将此基因经口服送入肠粘膜及系统淋巴组织，还有粘膜上皮组织。更重要的是此假病毒可以用作疫苗，将抗原的基因装入质粒，然后合成假病毒，经口服，可产生保护性的免疫反应。这一点与其他疫苗不同，是因为许多疫苗只能皮下或肌肉注射而不能口服。只能产生系统性免疫反应但不能产生粘膜免疫反应。因为许多致病菌是通过粘膜传染，所以只有此假病毒才可能产生有效的免疫反应来防止或治疗粘膜的致病菌的感染。这些致病菌包括细菌，比如沙门氏菌等。还有病毒，比如HIV(人免疫缺陷病毒)等。同时此病毒还可以用于诱导抗肿瘤免疫反应来治疗肿瘤，特别是粘膜肿瘤，比如结肠肿瘤。假病毒能诱导比基因疫苗更强的免疫反应。
实施例1首先将人乳头瘤病毒的外壳与解离缓冲液按1∶1体积混合、培养60min，室温，解离缓冲液为：乙二醇二(β-氨基乙醚)四乙酸(EGTA)20mM，二硫苏糖醇(DTT)40mM，氯化钠(NaCl)300mM，三(羟甲基)氨基甲烷盐酸盐(Tris-HCl)(PH8.0)100mM；然后加入1/10体积的质粒：0.51μg/μl的PCI-GLP-LCMV质粒，再将终止缓冲液逐步加入，终止缓冲液为：氯化钙(CaCl2)25mM，二甲基亚砜(DMSO)20％体积百分比，将混合好的混合液放在4℃过夜。用假病毒对C57BL6小鼠做免疫试验，用皮下注射方式注入小鼠体内，同时也将此种质粒直接注入其他小鼠的体内与其作对比试验，用Cr51释放试验，或r干扰素分泌试验(Elispot)。测出假病毒可以诱导出比质粒诱导出更多的特异性细胞毒细胞。因此在诱导细胞免疫反应上，假病毒疫苗比基因疫苗效用高。
实施例2
首先将牛乳头瘤病毒的外壳与解离缓冲液按1∶1体积混合、培养60min，室温，解离缓冲液为：乙二醇二(β-氨基乙醚)四乙酸(EGTA)20mM，二硫苏糖醇(DTT)40mM，氯化钠(NaCl)300mM，三(羟甲基)氨基甲烷盐酸盐(Tris-HCl)(PH8.0)100mM，然后加入1/10体积的1.0μg/μl的携带绿色荧光蛋白GLP的基因的质粒，再将终止缓冲液逐步加入，终止缓冲液为：氯化钙(CaCl2)25mM，二甲基亚砜(DMSO)20％体积百分比，将混合好的混合液放在4℃过夜。用此假病毒让小鼠口服(使用胃管)，然后检测GLP的表达。我们可以在肠粘膜、肠粘膜淋巴结，脾脏检测出GLP.此假病毒可以携带基因到粘膜及系统淋巴系统。因此，可以用于基因治疗。若用质粒本身口服则测不到GLP.
实施例3
用与实施例1同样的方法制备含有HPV16E7质粒的假病毒经口服来免疫动物，可诱导出粘膜及系统E7特异性的细胞毒细胞，然而直接用此质粒本身，则诱导不出免疫反应。因此此假病毒可以用于诱导粘膜及系统免疫反应。
实施例4
用于实施例1、2同样的方法制备含有HPV和BPV质粒的假病毒，然后用含有HPV的假病毒经口服免疫小鼠，然后用含有BPV的假病毒来感染小鼠，发现HPV假病毒可以防止BPV假病毒的感染。此假病毒可以用于提供免疫保护。
实施例5
用实施例1或实施例2的方法制备含有白介素-II的假病毒，用于提高粘膜反应的效率。经过口服进入肠粘膜淋巴组织和其他淋巴组织，提高对粘膜免疫诱导的效率。

Claims (3)

1.一种乳头瘤假病毒的制备方法，其特征在于：
(1)首先将人乳头瘤病毒样颗粒或牛乳头瘤病毒样颗粒与解离缓冲液1∶1体积混合，解离缓冲液为：乙二醇二(β-氨基乙醚)四乙酸(EGTA)20mM，二硫苏糖醇(DTT)40mM，氯化钠(NaCl)300mM，三(羟甲基)氨基甲烷盐酸盐(Tris-HCl)(PH8.0)100mM；
(2)加入1/10体积的质粒：0.5-1μg/μl的质粒；
(3)逐渐加入终止缓冲液，终止缓冲液为：氯化钙(CaCl2)25mM，二甲基亚砜(DMSO)20％体积百分比；
(4)混合好的混合液放在4℃过夜。
2.根据权利要求1所述的乳头瘤假病毒的制备方法，其特征在于：可将抗原基因插入质粒合成假病毒来制作疫苗。
3.根据权利要求1所述的乳头瘤假病毒的制备方法所制备的一种乳头瘤假病毒，其特征在于：它是由人乳头瘤病毒样颗粒或牛乳头瘤病毒样颗粒解离然后参入质粒，重新组合而成的人或牛乳头瘤假病毒。
CN01118003A 2001-05-15 2001-05-15 乳头瘤假病毒及其制备方法 Expired - Fee Related CN1114690C (zh)

Priority Applications (8)

Application Number Priority Date Filing Date Title
CN01118003A CN1114690C (zh) 2001-05-15 2001-05-15 乳头瘤假病毒及其制备方法
JP2001321828A JP4511090B2 (ja) 2001-05-15 2001-10-19 Ｄｎａプラスミドワクチン用アジュバンド及びその調製方法
PCT/CN2002/000187 WO2002092796A1 (en) 2001-05-15 2002-03-22 Papilloma pseud-virus and it's preparation
US10/294,087 US6878541B2 (en) 2001-05-15 2002-11-14 Papilloma pseudo-virus and preparation
US11/060,034 US7205126B2 (en) 2001-05-15 2005-02-17 Papilloma pseudovirus and preparation
US11/784,626 US8129144B2 (en) 2001-05-15 2007-04-09 Papilloma pseudovirus and preparation
JP2007124042A JP4472724B2 (ja) 2001-05-15 2007-05-09 パピロマウイルス偽ウイルス及びその調製方法
US13/413,386 US20120164173A1 (en) 2001-05-15 2012-03-06 Papilloma Pseudovirus and Preparation

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
CN01118003A CN1114690C (zh) 2001-05-15 2001-05-15 乳头瘤假病毒及其制备方法

Publications (2)

Publication Number Publication Date
CN1333338A CN1333338A (zh) 2002-01-30
CN1114690C true CN1114690C (zh) 2003-07-16

Family

ID=4662911

Family Applications (1)

Application Number Title Priority Date Filing Date
CN01118003A Expired - Fee Related CN1114690C (zh) 2001-05-15 2001-05-15 乳头瘤假病毒及其制备方法

Country Status (4)

Country Link
US (3) US6878541B2 (zh)
JP (2) JP4511090B2 (zh)
CN (1) CN1114690C (zh)
WO (1) WO2002092796A1 (zh)

Families Citing this family (18)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN1114690C (zh) * 2001-05-15 2003-07-16 乔良 乳头瘤假病毒及其制备方法
US20120164173A1 (en) * 2001-05-15 2012-06-28 Liang Qiao Papilloma Pseudovirus and Preparation
CA2604909A1 (en) 2005-04-15 2006-10-26 The Government Of The United States Of America, As Represented By The Se Cretary, Department Of Health And Human Services Methods and compositions for producing an enhanced immune response to a human papillomavirus immunogen
WO2008140961A2 (en) * 2007-05-08 2008-11-20 The Government Of The U.S.A, As Represented By The Secretary, Department Of Health And Human Services Papillomavirus pseudoviruses for detection and therapy of tumors
EP3427755B1 (en) 2009-04-13 2020-10-21 INSERM - Institut National de la Santé et de la Recherche Médicale Hpv particles and uses thereof
WO2011039646A2 (en) 2009-09-30 2011-04-07 Inserm (Institut National De La Sante Et De La Recherche Medicale) Papilloma virus -like particles for targeted gene delivery
ES2632431T3 (es) 2009-10-30 2017-09-13 Ntf Therapeutics, Inc. Moléculas de neurturina mejoradas
WO2013119877A1 (en) 2012-02-07 2013-08-15 Aura Biosciences, Inc. Virion-derived nanospheres for selective delivery of therapeutic and diagnostic agents to cancer cells
US8835387B2 (en) 2012-02-16 2014-09-16 Atyr Pharma, Inc. Histidyl-tRNA synthetases for treating autoimmune and inflammatory diseases
US10117947B2 (en) 2013-09-18 2018-11-06 Aura Biosciences, Inc. Virus-like particle conjugates for diagnosis and treatment of tumors
MA43134A (fr) 2015-10-30 2018-09-05 Aleta Biotherapeutics Inc Compositions et méthodes de transduction tumorale
BR112018008783A8 (pt) 2015-10-30 2019-02-26 Aleta Biotherapeutics Inc terapia-alvo de câncer
JP7115982B2 (ja) 2015-10-30 2022-08-09 アレタ・バイオセラピューティクス・インコーポレイテッド 癌の治療のための組成物及び方法
US10751398B2 (en) * 2016-10-07 2020-08-25 Loyola University Chicago Inflammasome activators and methods of use to treat tumors
SG11201912480SA (en) * 2017-06-23 2020-01-30 Pathovax Llc Chimeric virus-like particles and uses thereof as antigen-specific redirectors of immune responses
KR20250044945A (ko) 2017-11-06 2025-04-01 더 유나이티드 스테이츠 오브 어메리카, 애즈 리프리젠티드 바이 더 세크러테리, 디파트먼트 오브 헬쓰 앤드 휴먼 서비씨즈 기존의 미생물 면역을 활용한 암 치료
EP3710468A1 (en) 2017-11-14 2020-09-23 Fraunhofer Gesellschaft zur Förderung der angewandten Forschung e.V. Non-human papillomaviruses for gene delivery in vitro and in vivo
WO2020139978A1 (en) 2018-12-27 2020-07-02 Verimmune Llc Conjugated virus-like particles and uses thereof as anti-tumor immune redirectors

Family Cites Families (8)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
DE19526752C2 (de) * 1995-07-21 1997-08-07 Lutz Prof Dr Gissmann Hocheffiziente Bildung von Papillomavirusähnlichen Partikeln
FR2749323B1 (fr) * 1996-06-04 1998-07-10 Pasteur Merieux Serums Vacc Pseudo-particules virales utiles en tant que vecteur de delivrance d'acide nucleique
DE69734829D1 (de) * 1996-07-17 2006-01-12 Us Health Infektiöse pseudovirale papillomavirus partikel
ES2268787T3 (es) * 1997-09-05 2007-03-16 Medimmune, Inc. Metodo in vitro de desmontaje/embalaje de particulas similares a virus (vlp) de papilomavirus.
GB9806666D0 (en) * 1998-03-27 1998-05-27 Stanley Margaret Antigen preparation and use
CN1241636A (zh) * 1999-07-05 2000-01-19 第一军医大学珠江医院 抗hpv16e6核酶质粒及其在人乳头瘤病毒与肿瘤治疗中的应用
GB0007231D0 (en) * 2000-03-24 2000-05-17 Chiron Spa Modified rna for gene delivery
CN1114690C (zh) 2001-05-15 2003-07-16 乔良 乳头瘤假病毒及其制备方法

Also Published As

Publication number Publication date
WO2002092796A1 (en) 2002-11-21
JP4511090B2 (ja) 2010-07-28
JP2003024058A (ja) 2003-01-28
US8129144B2 (en) 2012-03-06
CN1333338A (zh) 2002-01-30
US7205126B2 (en) 2007-04-17
JP4472724B2 (ja) 2010-06-02
US6878541B2 (en) 2005-04-12
US20050142115A1 (en) 2005-06-30
US20030129728A1 (en) 2003-07-10
US20100255027A1 (en) 2010-10-07
JP2007211026A (ja) 2007-08-23

Similar Documents

Publication Publication Date Title
CN1114690C (zh) 乳头瘤假病毒及其制备方法
JP5153984B2 (ja) 口蹄疫に対するワクチン
CN108567974B (zh) 一种防治新型鹅星状病毒的灭活疫苗及其制备方法
CN1284883A (zh) 增强核酸接种的免疫应答的方法
EP2802349B1 (en) Immunogenic hpv l2-containing vlps and related compositions and methods
US6368602B1 (en) Mucosal immunization against hepatitis A virus (HAV) through rectal administration of HAV vaccine
CN105497886A (zh) 乙肝核心抗原病毒样颗粒作为肿瘤治疗性疫苗载体的应用
JP2003523401A (ja) 粘膜体表面に接触させてワクチン抗原を包含する物質の効果を調節する新規非抗原性粘膜アジュバント処方
JP7777890B2 (ja) Ｃｃｌ１１の用途
BR112019027488A2 (pt) partículas semelhantes a vírus quiméricas e usos destas como redirecionadores de respostas imunológicas antígeno-específicos
CN116200394A (zh) CpG寡聚脱氧核苷酸及其应用
US20110142873A1 (en) Bioactive purified hspe7 compositions
CN116763933A (zh) mRNA疫苗递送载体、mRNA疫苗及其制备方法和应用
Lu et al. Enhanced protective immune response of foot-and-mouth disease vaccine through DNA-loaded virus-like particles
CN119113096A (zh) 防治SARS-CoV-2变异株JN.1、BA.2.86和XBB谱系的重组蛋白疫苗、联合用药物及用途
Somavarapu et al. Oral plasmid DNA delivery systems for genetic immunisation
CN102266551B (zh) 可用于治疗人或动物免疫相关性疾病的白介素-4治疗性疫苗
CN114470186B (zh) 一种可吸入式纳米新冠疫苗的制备方法
US20120164173A1 (en) Papilloma Pseudovirus and Preparation
CN107456574B (zh) 一种无佐剂单剂量HBsAg纳米凝胶疫苗及其制备方法
KR102092258B1 (ko) 광감각제가 접합된 고분자를 유효성분으로 포함하는 면역증강제, 바이러스 감염 또는 암 예방 또는 치료용 백신 조성물
CN105727278B (zh) 一种羊口疮重组蛋白抗原疫苗及其制备方法
Shi et al. Astragalus Polysaccharide Nanoemulsion: A Promising Adjuvant for Foot‐And‐Mouth Disease Virus‐Like Particle Vaccines
CN1322120C (zh) 乙肝乙脑双价疫苗
KR20120076396A (ko) 독성약화된 토끼 믹소마바이러스를 기본으로 한 모노파라뮤니티 유발인자

Legal Events

Date Code Title Description
C10 Entry into substantive examination
SE01 Entry into force of request for substantive examination
C06 Publication
PB01 Publication
C14 Grant of patent or utility model
GR01 Patent grant
REG Reference to a national code

Ref country code: HK

Ref legal event code: GR

Ref document number: 1057795

Country of ref document: HK

C17 Cessation of patent right
CF01 Termination of patent right due to non-payment of annual fee

Granted publication date: 20030716

Termination date: 20140515