WO2011079817A1 - Dendrimère de tuftsine et protéine de matrice de la grippe, et son utilisation - Google Patents

Dendrimère de tuftsine et protéine de matrice de la grippe, et son utilisation Download PDF

Info

Publication number
WO2011079817A1
WO2011079817A1 PCT/CN2010/080595 CN2010080595W WO2011079817A1 WO 2011079817 A1 WO2011079817 A1 WO 2011079817A1 CN 2010080595 W CN2010080595 W CN 2010080595W WO 2011079817 A1 WO2011079817 A1 WO 2011079817A1
Authority
WO
WIPO (PCT)
Prior art keywords
branched
lys
influenza
influenza virus
tuftsin
Prior art date
Application number
PCT/CN2010/080595
Other languages
English (en)
Chinese (zh)
Inventor
张智清
刘晓宇
郭建强
徐一
韩苏
姚立红
陈爱珺
Original Assignee
中国疾病预防控制中心病毒病预防控制所
元森泰生物科技（天津）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 中国疾病预防控制中心病毒病预防控制所, 元森泰生物科技（天津）有限公司 filed Critical 中国疾病预防控制中心病毒病预防控制所
Publication of WO2011079817A1 publication Critical patent/WO2011079817A1/fr

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
    • A61K39/145—Orthomyxoviridae, e.g. influenza virus
    • 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
    • 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
    • A61P31/16—Antivirals for RNA viruses for influenza or rhinoviruses
    • 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
    • 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
    • A61K2039/55516—Proteins; Peptides
    • 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
    • A61K2039/64—Medicinal preparations containing antigens or antibodies characterised by the architecture of the carrier-antigen complex, e.g. repetition of carrier-antigen units
    • A61K2039/645—Dendrimers; Multiple antigen peptides
    • 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
    • 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
    • C12N2760/00—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA ssRNA viruses negative-sense
    • C12N2760/00011—Details
    • C12N2760/16011—Orthomyxoviridae
    • C12N2760/16022—New viral proteins or individual genes, new structural or functional aspects of known viral proteins or genes
    • 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
    • C12N2760/00—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA ssRNA viruses negative-sense
    • C12N2760/00011—Details
    • C12N2760/16011—Orthomyxoviridae
    • C12N2760/16034—Use of virus or viral component as vaccine, e.g. live-attenuated or inactivated virus, VLP, viral protein

Definitions

  • the invention relates to a branched polypeptide with an immunologically active peptide as a carrier and a derivative thereof and application thereof, in particular to a branched polypeptide having immunogenicity of influenza virus.
  • the invention provides a branched polypeptide and a derivative thereof and an application thereof, and one of the objects is to provide a A highly immunogenic branched polypeptide.
  • Hydroxylation, carboxylation, carbonylation, methylation, acetylation, phosphorylation, esterification or glycosylation may be carried out on the amino acid side chain group of the branched polypeptide, at the amino terminus or the carboxy terminus, Branched polypeptide derivatives.
  • the branched polypeptide can be reacted with an acid or a base to form a pharmaceutically acceptable salt compound.
  • An equivalent change can be made to the branched polypeptide of the present invention to obtain the following branched polypeptide:
  • Another object of the invention is to provide the use of said branched polypeptides and derivatives thereof.
  • the sputum influenza virus includes H1N1 influenza virus, H2N2 influenza virus, H3N2 influenza virus, H5N1 influenza virus, H7N7 influenza virus, and H9N2 influenza virus.
  • Figure 1 is a schematic diagram of the branched (M2e) 4- Tuft sin structure.
  • Figure 2 shows the results of the branched (M2e) 4-Tuftsin HPLC analysis.
  • Figure 3 shows the results of the branched (M2e) 4-Tuftsin mass spectrometry.
  • Figure 6 shows the titer of M2e antibody in serum of immunized mice by ELISA.
  • Figure 9 is a schematic diagram of the branched (M2e) 8- Tuftsin structure.
  • Figure 10 shows the results of ELISA for detection of branched (M2e) 8- Tuftsin antigenicity.
  • Figure 11 shows the binding of FITC-labeled branched (M2e) 8-Tuftsin to macrophages (400
  • Figure 12 is a graph showing the titer of serum M2e antibody in mice by Example 2 ELISA.
  • Figure 14 is a graph showing the results of detecting the lung viral load of the mouse of Example 1. The best way to achieve this embodiment 1
  • the four-branched polypeptide (M2e) 4- Tuftsin shown in Figure 1 was synthesized by solid phase synthesis using a peptide synthesizer.
  • the structural formula of the branched peptide from N-terminus to C-terminus was (Ser- Leu-Leu- Thr-Glu_Va 1- Glu-Thr-Pro-Ile-Arg-Asn-Glu-Trp-Gly-Cys-Arg-Cys-Asn-As-Ser-Se r-Asp ) 4 - ( Lys ) 2 - Lys- Thr- Lys-Pro_Arg.
  • the structural formula of the branched peptide (M2e) 4-G4 from the N-terminus to the C-terminus is ( Ser- Leu_Leu_Thr-Glu-Val-Glu-Thr-Pro-I le-Arg-Asn-Glu-Trp-Gly-Cys-Arg-Cys- Asn-Asp-Ser-Ser -Asp) 4 - (Lys) -Lys-Gly-Gly-Gly-Gly-Gly 0
  • the above 96-well plates were divided into two groups of 48 wells each.
  • FITC-labeled branched (M2e) 4-Tuftsin One group was added with FITC-labeled branched (M2e) 4-Tuftsin, and the final concentration of branched (M2e) 4-Tuftsin was 0.5 mol/L; the other group was added with FITC-labeled branched peptide (M2e)4 per well.
  • - G4 branched (M2e) 4- G4 with a final concentration of 0.5 ⁇ mol/L, mixed, cultured at 4 °C 20 minutes.
  • PBS group was injected with PBS and the inside muscle of each Al 10 ⁇ 1 in the two hind legs of mice (0H) 3 mixture of adjuvant, PBS with Al (0H) 3 adjuvant and PBS A1 (03 ⁇ 4 3 adjuvant The volume ratio is 1:1.
  • the M2e monomer group was prepared by injecting 10 ⁇ l of M2e monomer and Al(0H) 3 adjuvant into the inner muscles of the hind legs of the mice, and the concentration of the M2e monomer in the influenza vaccine was 5 ug/10 ul. The total amount of M2e monomer injected per mouse was 10 ⁇ g/head.
  • the 4_Tuftsin group was prepared by injecting 10 ⁇ l of branched (M2e)4-Tuftsin and Al(OH) 3 adjuvant into the inner muscles of the hind legs of the mice.
  • the influenza vaccine was branched (M2e).
  • 4- Tufts in total injection volume is 10 ⁇ ⁇ / only.
  • the 4-G4 group was injected with 10 ⁇ M of branched peptide (M2e) in the inner muscles of the hind legs of the mice.
  • 4-G4 and Al (OH) 3 adjuvant, branched peptide (M2e) 4-G4 and Al (OH) 3 adjuvant in a mixture of branched peptide (the M2e) 4_G4 concentration of 5ug / 10ul o branched peptide (the M2e) of each mouse was injected 4-G4 total 10 ⁇ ⁇ / only.
  • mice Each group of mice was immunized twice, with each immunization interval of two weeks.
  • Serum anti-M2e antibody titers were measured by ELISA on the 14th day after immunization of mice in different immunization groups.
  • mice in each group were sacrificed to obtain spleens, and spleen lymphocytes were isolated for ELISP0T test.
  • the ELISP0T method was used to detect the number of cells secreting IFN- ⁇ after stimulation of splenic lymphocytes with M2e polypeptide, which indirectly reflected the specific response of mouse Thl cells after immunization.
  • ELISP0T test The results of ELISP0T test are shown in Fig. 7.
  • the average spleen lymphocytes produced 6 spots per 1 ⁇ 10 ⁇ cells
  • the M2e monomer group spleen lymphocytes produced 46 spots per 1 ⁇ 10 ⁇ cells.
  • (M2e) 4- Tuftsin group spleen lymphocytes produced an average of 254 spots per 1 ⁇ 10 6 cells
  • (M2e) 4-G4 group spleen lymphocytes produced an average of 156 spots per 1 ⁇ 10 6 cells .
  • each group of remaining mice was challenged with the influenza virus PR8 strain, and the influenza virus attack method was as follows: The mice were anesthetized by the CO 2 inhalation method, and then 10 drops were directly dropped into the nostrils on both sides thereof. LD 5 .
  • the influenza virus PR8 strain of virus fluid makes it fully inhaled.
  • 2 mice in each group were sacrificed to take the lungs, weighed, and the lung tissue suspension was prepared. After serial dilution, the MDCK cells were inoculated and the influenza virus titer (TCID 5 ) was determined. Pulmonary viral load assays showed lg TCID 5 in the PBS group.
  • mice After the challenge, the survival of each group of mice was observed daily, and the survival rate was measured 14 days after the challenge. The mice that died within 24 hours of the challenge were considered as accidental death.
  • mice Nine mice died after challenge with PBS, and 7 mice died from M2e monomer.
  • the octahedral polypeptide (M2e) 8- Tuftsin shown in Figure 9 was synthesized by solid phase synthesis using a peptide synthesizer.
  • the structural formula of the branched peptide from N to C was (Ser- Leu-Leu- Thr-Glu_Va 1- Glu-Thr-Pro-Ile-Arg-Asn-Glu-Trp-Gly-Cys-Arg-Cys-Asn-As-Ser-Se r-Asp ) s - ( Lys ) - ( Lys ) 2 - ys_Thr- ys- Pro- Arg.
  • the branched polypeptides synthesized above were subjected to high performance liquid chromatography and mass spectrometry.
  • peptide synthesized by the peptide synthesizer was a branched polypeptide designed by us, which was named as branched (M2e) 8- Tuftsin with a molecular weight of 22251 Da.
  • Branched (M2e) 8-Tuf ts in concentrations of 0.0625 ⁇ ⁇ , 0.125 ⁇ g, 0.25 ⁇ g, 0.5 ⁇ g, and 1 ⁇ g were individually coated into wells of an ELISA plate, and recombinant avian influenza expressed in E. coli
  • the virus ⁇ 2 protein was used as a positive control.
  • Mouse anti- ⁇ 2 polyclonal antibody was used as primary antibody and secondary antibody was alkaline Phosphatase labeled goat anti-mouse immunoglobulin IgG antibody.
  • the ELISA results are shown in Figure 10.
  • the branched (M2e) 8-Tuf tsin specifically recognizes and binds to the anti-M2 polyclonal antibody when the branched (M2e) 8-Tuftsin coating is 0.0625 ⁇ g/well to 0.25. In the g/pore range, the absorbance value is proportional to it, and the branch (M2e) 8- Tuftsin amount is between 0.25 ⁇ g/well and 1 ⁇ g/well, and the absorbance value reaches the plateau.
  • Description Branched (M2e) 8-Tuftsin has influenza A virus M2 antigen activity.
  • the structural formula of the branched peptide (M2e) 8-G4 from the N-terminus to the C-terminus is ( Ser- Leu-Leu-Thr-Glu-Val - Glu - Thr - Pro - I le-Arg-Asn-Glu-Trp-Gly-Cys- Arg-Cys-Asn-Asp-Ser-Ser -Asp ) 8 - ( Lys ) 4- ( Lys ) Plant! ⁇ ys - Gly - Gly - Gly - Gly - Gly.
  • fluorescein FITC-labeled branched (M2e) 8-Tuftsin macrophage was determined using fluorescein FITC-labeled branched peptide (M2e) 8-G4 as a control.
  • the specific method is as follows:
  • BALB/c mouse peritoneal macrophages were cultured in 96-well plate 1640 medium at 37 ° C 5% C0 2 for 7 h, 2 X 107 ml peritoneal macrophages per well, and the upper suspension cells were discarded. Wall macrophages were cultured at 4 ° C for 40 minutes.
  • the above 96-well plates were divided into two groups of 48 wells each.
  • FITC-labeled branched (M2e) 8- Tuftsin One group was added with FITC-labeled branched (M2e) 8- Tuftsin, and the final concentration of branched (M2e) 8-Tuftsin was 0.5 m ⁇ l/L; the other group was added with FITC-labeled branched peptide (M2e) per well.
  • 8-G4 branched (M2e) 8- G4 with a final concentration of 0.5 ⁇ mol/L, mixed and incubated at 4 ° C for 20 minutes.
  • the cells were then washed twice with 1640 medium, and the washed cells were observed under an Olympus 1X-51FL fluorescence microscope.
  • Figure 11A is an image of the FITC-labeled branched (M2e) 8-Tuftsin and mouse peritoneal macrophages after incubation
  • Figure 11B is the FI TC-labeled branch ( M2 e) Image of 8 -Tuf tsin and mouse peritoneal macrophages after incubation with ultraviolet light, green fluorescence was observed on the cell surface, and the results of Fig. 11A and Fig.
  • mice Six-week-old female BALB/c mice were randomly divided into three groups: PBS group, (M2e) 8-Tuftsin group, and (M2e) 8-G4 group, 20 BALB/c mice in each group.
  • (M2e) 8-Tuftsin group is a flu vaccine prepared by injecting 30 ⁇ l of branched (M2e) 8-Tuftsin and incomplete Freund's adjuvant into the skin of the two hind legs of the mice.
  • M2e) 8- Tuftsin concentration was 5ug/30uL.
  • the total amount of branching (M2e) 8- Tuftsin injected per mouse was 10Og/mo.
  • mice Each group of mice was immunized three times, with each immunization interval of three weeks.
  • mice in each group were sacrificed to obtain spleens, and spleen lymphocytes were isolated for ELISP0T test.
  • the number of cells that specifically stimulate M2e-stimulated IFN- ⁇ by ELISP0T method indirectly reflects the specific response function of 'Th” and murine Th 1 cells.
  • the ELISP0T method uses the Quick Spot Human IFN- ⁇ ELISP0T pre-coated kit.
  • the branched (M2e) 8-Tuftsin can induce cellular immunity in mice, and the number of spots produced is significantly different from the number of spots induced by PBS (P ⁇ 0.05), while the control branch peptide (M2e) 8-G4 is induced. The number of spots is significantly lower than that of the branch peptide containing Tuftsin.
  • influenza virus PR8 14 days after the third immunization, the remaining mice were challenged with the influenza virus PR8 strain.
  • the influenza virus PR8 challenge method was as follows: The mice were anesthetized by CO 2 inhalation, and then rapidly instilled into the nostrils on both sides. ⁇ 1 5 times TCID 5 . Influenza virus PR8 virus solution, allowing it to be inhaled adequately. On the 5th day after challenge, 5 mice in each group were sacrificed to take lungs, weighed, and lung tissue suspensions were prepared. After serial dilution, MDCK cells were inoculated and TCID 5 was determined. .
  • Pulmonary viral load assay results are shown in Figure 14, PBS group lg TCID 5 . Is 6.53, (M2e) 8-Tuftsin&lg TCID 5 . It is 5.53, (M2e)8 - G4 group lg TCID 5 . The result was 5.89. This result showed that the lung virus load of the mice with branching peptide containing Tuftsin was the lowest, which was significantly different from that of the PBS group (P ⁇ 0.05), indicating that the replication of the virus in this group of mice was effectively inhibited. .
  • mice inoculated with the control branch peptide (M2e) 8-G4 had 1 on the 8th day. Death, while mice inoculated with branched (M2e) S-Tuftsin did not die, indicating that the two branched peptide immunizations have protective effects on mice.
  • branched polypeptide derivative which is on the amino acid side chain group of branched (M2e)4-11! ⁇ 3111 and branched ( ⁇ 126) 8-Tuftsin, and an amino terminal.
  • a derivative obtained by hydroxylation, carboxylation, coagulation, methylation, acetylation, phosphorylation, esterification or glycosylation at the carboxy terminus is also provided.
  • branched (M2e) 4-Tuftsin and branched (M2e) 8-Tuftsin pharmaceutically acceptable salts which are branched (M2e) 4-Tuf ts in and branched ( M2e) 8-Tuftsin is available as a raw material in combination with prior art preparation methods.
  • the branched (M2 e) 4-Tuf tsin and the branched (M2 e) 8-Tuf tsin proposed by the present invention can be used for preparing a vaccine, in particular, preparing an influenza A virus vaccine, and further, the influenza A virus It is an H1N1 influenza virus, an H2N2 influenza virus, an H3N2 influenza virus, an H5N1 influenza virus, an H7N7 influenza virus or an H9N2 influenza virus.
  • the present invention also proposes a vaccine comprising branched (M2e) 4-Tuf tsin or branched (M2e) 8-Tuftsin as an active component.
  • the vaccine is a sputum influenza virus vaccine.
  • influenza A virus vaccine is an H1N1 influenza virus vaccine, an H2N2 influenza virus vaccine, an H3N2 influenza virus vaccine, an H5N1 influenza virus vaccine, an H7N7 influenza virus vaccine or an H9N2 influenza virus. vaccine.
  • the branched polypeptide of the present invention can be prepared into an influenza vaccine.
  • the branched polypeptide of the present invention can specifically bind to an M2 polyclonal antibody, and can specifically bind to macrophages to promote treatment of antigen presenting cells.
  • the vaccine prepared from the branched polypeptide of the present invention induces an animal immune response with high efficiency and protects the animal from viral infection.

Landscapes

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

Abstract

La présente invention concerne un dendrimère ou son dérivé qui comprend le domaine extracellulaire de la protéine 2 de matrice de la grippe, un liant et la TUFTSINE. La formule du dendrimère est (AAN)8-(Lys)4-(Lys)2-Lys-Thr-Lys-Pro-Arg ou (AAN)4-(Lys)2-Lys-Thr-Lys-Pro-Arg, la séquence d'acides aminés de AAN étant de préférence Ser-Leu-Leu-Thr-Glu-Val-Glu-Thr-Pro-Ile-Arg-Asn-Glu-Trp-Gly-Cys-Arg-Cys-Asn-Asp-Ser-Ser-Asp. Le dendrimère peut être utilisé pour détecter des anticorps polyclonaux de la protéine 2 de matrice de la grippe et pour stimuler les macrophages afin qu'ils activent les cellules présentatrices d'antigène. La présente invention concerne en outre un vaccin comprenant le dendrimère ou son dérivé pour inhiber le virus de la grippe.
PCT/CN2010/080595 2009-12-31 2010-12-31 Dendrimère de tuftsine et protéine de matrice de la grippe, et son utilisation WO2011079817A1 (fr)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
CN200910312897 2009-12-31
CN200910312897.0 2009-12-31

Publications (1)

Publication Number Publication Date
WO2011079817A1 true WO2011079817A1 (fr) 2011-07-07

Family

ID=44226186

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/CN2010/080595 WO2011079817A1 (fr) 2009-12-31 2010-12-31 Dendrimère de tuftsine et protéine de matrice de la grippe, et son utilisation

Country Status (2)

Country Link
CN (1) CN102153654B (fr)
WO (1) WO2011079817A1 (fr)

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2017058114A1 (fr) * 2015-10-01 2017-04-06 Nanyang Technological University Ligature de peptides médiée par la butelase

Families Citing this family (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN103961685B (zh) * 2014-01-09 2016-05-11 中国人民解放军总医院第一附属医院 一种用于脓毒症治疗的t-肽免疫调节剂
CN105085637A (zh) * 2014-05-07 2015-11-25 北京英诺泰生物技术有限公司 一种多肽化合物及其应用
CN106317216B (zh) * 2016-09-21 2019-07-19 南京农业大学 一种促进h9n2禽流感疫苗免疫效果的活性肽及应用
CN108196073B (zh) * 2018-03-13 2019-09-13 江苏浩欧博生物医药股份有限公司 一种测定抗环瓜氨酸肽抗体的试剂盒及其应用

Citations (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0225648A2 (fr) * 1985-12-13 1987-06-16 Yeda Research And Development Company, Ltd. Composition de matière à activité antigénique fortement accrue
EP0450715A1 (fr) * 1990-04-02 1991-10-09 ENIRICERCHE S.p.A. Composés immunogènes, procédé en vue de leur synthèse et leur utilisation dans des vaccins contre la malaria
CN101007846A (zh) * 2006-01-24 2007-08-01 韩苏 一种t8合成产物及其用途
CN101007842A (zh) * 2006-01-24 2007-08-01 韩苏 一种t4合成产物及其用途
CN101015690A (zh) * 2006-02-08 2007-08-15 河南省生物工程技术研究中心 广谱流行性感冒疫苗的研制和应用
WO2009026465A2 (fr) * 2007-08-21 2009-02-26 Dynavax Technologies Corporation Composition et procédés de fabrication et d'utilisation de protéines de la grippe

Family Cites Families (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2003064452A2 (fr) * 2002-01-29 2003-08-07 MAX-PLANCK-Gesellschaft zur Förderung der Wissenschaften e.V. Methode de preparation de polypeptides hautement ramifies
CN101085806A (zh) * 2006-06-07 2007-12-12 韩苏 一种合成方式及其产物的用途

Patent Citations (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0225648A2 (fr) * 1985-12-13 1987-06-16 Yeda Research And Development Company, Ltd. Composition de matière à activité antigénique fortement accrue
EP0450715A1 (fr) * 1990-04-02 1991-10-09 ENIRICERCHE S.p.A. Composés immunogènes, procédé en vue de leur synthèse et leur utilisation dans des vaccins contre la malaria
CN101007846A (zh) * 2006-01-24 2007-08-01 韩苏 一种t8合成产物及其用途
CN101007842A (zh) * 2006-01-24 2007-08-01 韩苏 一种t4合成产物及其用途
CN101015690A (zh) * 2006-02-08 2007-08-15 河南省生物工程技术研究中心 广谱流行性感冒疫苗的研制和应用
WO2009026465A2 (fr) * 2007-08-21 2009-02-26 Dynavax Technologies Corporation Composition et procédés de fabrication et d'utilisation de protéines de la grippe

Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2017058114A1 (fr) * 2015-10-01 2017-04-06 Nanyang Technological University Ligature de peptides médiée par la butelase
US11091786B2 (en) 2015-10-01 2021-08-17 Nanyang Technological University Butelase-mediated peptide ligation

Also Published As

Publication number Publication date
CN102153654A (zh) 2011-08-17
CN102153654B (zh) 2012-10-10

Similar Documents

Publication Publication Date Title
JP6826027B2 (ja) インフルエンザ抗原送達用のベクターおよび構築体
US10137190B2 (en) Nucleic acid molecules encoding ferritin-hemagglutinin fusion proteins
AU570929B2 (en) Broad spectrum influenza antisera
JP7183149B2 (ja) 安定化されたグループ２インフルエンザヘマグルチニンステム領域三量体およびその使用
US4625015A (en) Broad spectrum influenza antisera
CN104066446A (zh) 流感病毒疫苗及其用途
WO2011079817A1 (fr) Dendrimère de tuftsine et protéine de matrice de la grippe, et son utilisation
US9198965B2 (en) Peptide adjuvant for influenza vaccination
CN110003314B (zh) H1n1流感病毒血凝素可诱发广谱保护性抗体的表位肽及其应用
US10195266B2 (en) Versatile influenza virus vaccine composition
Stropkovská et al. Broadly cross-reactive monoclonal antibodies against HA2 glycopeptide of Influenza A virus hemagglutinin of H3 subtype reduce replication of influenza A viruses of human and avian origin
KR101557191B1 (ko) 넓은 범위의 방어능력을 갖는 인플루엔자 단독 또는 보강 백신
CN101087808A (zh) 流行性感冒病毒蛋白质的组合物及其使用方法
US20120156242A1 (en) An Antigenic Peptide Derived From Influenza Virus And A Method For Selecting Anti-Influenza Virus Antibody
CN103705917A (zh) M2e合成肽猪流感病毒通用疫苗及其应用
KR20130001559A (ko) 넓은 범위의 교차 방어능력을 갖는 신규한 보강 인플루엔자 백신

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: 10840604

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: 10840604

Country of ref document: EP

Kind code of ref document: A1