WO2001062282A2 - Adjuvants for vaccines - Google Patents
Adjuvants for vaccines Download PDFInfo
- Publication number
- WO2001062282A2 WO2001062282A2 PCT/GB2001/000816 GB0100816W WO0162282A2 WO 2001062282 A2 WO2001062282 A2 WO 2001062282A2 GB 0100816 W GB0100816 W GB 0100816W WO 0162282 A2 WO0162282 A2 WO 0162282A2
- Authority
- WO
- WIPO (PCT)
- Prior art keywords
- adjuvant
- responses
- vaccine
- homoserine lactone
- active agent
- Prior art date
Links
- 239000002671 adjuvant Substances 0.000 title claims abstract description 30
- 229960005486 vaccine Drugs 0.000 title claims abstract description 25
- 230000004044 response Effects 0.000 claims abstract description 18
- 239000000203 mixture Substances 0.000 claims abstract description 16
- 210000002443 helper t lymphocyte Anatomy 0.000 claims abstract description 11
- QJPWUUJVYOJNMH-VKHMYHEASA-N L-homoserine lactone Chemical compound N[C@H]1CCOC1=O QJPWUUJVYOJNMH-VKHMYHEASA-N 0.000 claims abstract description 7
- 230000002708 enhancing effect Effects 0.000 claims abstract description 6
- 239000013543 active substance Substances 0.000 claims description 8
- 208000015181 infectious disease Diseases 0.000 claims description 8
- 150000001875 compounds Chemical class 0.000 claims description 7
- PHSRRHGYXQCRPU-AWEZNQCLSA-N N-(3-oxododecanoyl)-L-homoserine lactone Chemical compound CCCCCCCCCC(=O)CC(=O)N[C@H]1CCOC1=O PHSRRHGYXQCRPU-AWEZNQCLSA-N 0.000 claims description 6
- 238000004519 manufacturing process Methods 0.000 claims description 5
- 102000004169 proteins and genes Human genes 0.000 claims description 4
- 108090000623 proteins and genes Proteins 0.000 claims description 4
- 230000020192 tolerance induction in gut-associated lymphoid tissue Effects 0.000 claims description 4
- 230000002265 prevention Effects 0.000 claims description 3
- 206010044708 Trypanosomal infections Diseases 0.000 claims description 2
- 238000002560 therapeutic procedure Methods 0.000 claims description 2
- 108090000765 processed proteins & peptides Proteins 0.000 claims 1
- 201000010099 disease Diseases 0.000 description 5
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 5
- 230000002163 immunogen Effects 0.000 description 5
- 239000000427 antigen Substances 0.000 description 4
- 230000028993 immune response Effects 0.000 description 4
- 102000036639 antigens Human genes 0.000 description 3
- 108091007433 antigens Proteins 0.000 description 3
- 230000000694 effects Effects 0.000 description 3
- UKAUYVFTDYCKQA-UHFFFAOYSA-N -2-Amino-4-hydroxybutanoic acid Natural products OC(=O)C(N)CCO UKAUYVFTDYCKQA-UHFFFAOYSA-N 0.000 description 2
- 208000023275 Autoimmune disease Diseases 0.000 description 2
- 108010002350 Interleukin-2 Proteins 0.000 description 2
- 102000000588 Interleukin-2 Human genes 0.000 description 2
- 229940037003 alum Drugs 0.000 description 2
- 210000004027 cell Anatomy 0.000 description 2
- 230000036755 cellular response Effects 0.000 description 2
- 238000011260 co-administration Methods 0.000 description 2
- 239000003085 diluting agent Substances 0.000 description 2
- LOKCTEFSRHRXRJ-UHFFFAOYSA-I dipotassium trisodium dihydrogen phosphate hydrogen phosphate dichloride Chemical compound P(=O)(O)(O)[O-].[K+].P(=O)(O)([O-])[O-].[Na+].[Na+].[Cl-].[K+].[Cl-].[Na+] LOKCTEFSRHRXRJ-UHFFFAOYSA-I 0.000 description 2
- 229940079593 drug Drugs 0.000 description 2
- 239000003814 drug Substances 0.000 description 2
- 239000000284 extract Substances 0.000 description 2
- 210000000987 immune system Anatomy 0.000 description 2
- 210000002540 macrophage Anatomy 0.000 description 2
- 238000000034 method Methods 0.000 description 2
- 239000002953 phosphate buffered saline Substances 0.000 description 2
- 238000012360 testing method Methods 0.000 description 2
- 241000589155 Agrobacterium tumefaciens Species 0.000 description 1
- 241000894006 Bacteria Species 0.000 description 1
- 241000588832 Bordetella pertussis Species 0.000 description 1
- 102000008186 Collagen Human genes 0.000 description 1
- 108010035532 Collagen Proteins 0.000 description 1
- 208000035473 Communicable disease Diseases 0.000 description 1
- 241000588914 Enterobacter Species 0.000 description 1
- 206010020376 Hookworm infection Diseases 0.000 description 1
- 102000008070 Interferon-gamma Human genes 0.000 description 1
- 108010074328 Interferon-gamma Proteins 0.000 description 1
- 108090000978 Interleukin-4 Proteins 0.000 description 1
- 108010002616 Interleukin-5 Proteins 0.000 description 1
- UKAUYVFTDYCKQA-VKHMYHEASA-N L-homoserine Chemical class OC(=O)[C@@H](N)CCO UKAUYVFTDYCKQA-VKHMYHEASA-N 0.000 description 1
- 241001529936 Murinae Species 0.000 description 1
- 241000498270 Necator americanus Species 0.000 description 1
- 241000588701 Pectobacterium carotovorum Species 0.000 description 1
- 108010033276 Peptide Fragments Proteins 0.000 description 1
- 102000007079 Peptide Fragments Human genes 0.000 description 1
- 241000589516 Pseudomonas Species 0.000 description 1
- 241000607720 Serratia Species 0.000 description 1
- 230000024932 T cell mediated immunity Effects 0.000 description 1
- 102000009270 Tumour necrosis factor alpha Human genes 0.000 description 1
- 108050000101 Tumour necrosis factor alpha Proteins 0.000 description 1
- 241000607598 Vibrio Species 0.000 description 1
- 241000607734 Yersinia <bacteria> Species 0.000 description 1
- 230000004913 activation Effects 0.000 description 1
- 238000009175 antibody therapy Methods 0.000 description 1
- 238000013459 approach Methods 0.000 description 1
- 230000002238 attenuated effect Effects 0.000 description 1
- 210000003719 b-lymphocyte Anatomy 0.000 description 1
- 230000001580 bacterial effect Effects 0.000 description 1
- 239000012620 biological material Substances 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- 229920001436 collagen Polymers 0.000 description 1
- 210000001151 cytotoxic T lymphocyte Anatomy 0.000 description 1
- 210000003979 eosinophil Anatomy 0.000 description 1
- 238000009472 formulation Methods 0.000 description 1
- 229940044627 gamma-interferon Drugs 0.000 description 1
- -1 homoserine lactone compound Chemical class 0.000 description 1
- 208000029437 hookworm infectious disease Diseases 0.000 description 1
- 230000008105 immune reaction Effects 0.000 description 1
- 230000036039 immunity Effects 0.000 description 1
- 230000006698 induction Effects 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 244000005700 microbiome Species 0.000 description 1
- 201000006417 multiple sclerosis Diseases 0.000 description 1
- 206010039073 rheumatoid arthritis Diseases 0.000 description 1
- 239000000021 stimulant Substances 0.000 description 1
- 238000007910 systemic administration Methods 0.000 description 1
- 230000009885 systemic effect Effects 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
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
- A61K39/39—Medicinal preparations containing antigens or antibodies characterised by the immunostimulating additives, e.g. chemical adjuvants
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
- A61P37/02—Immunomodulators
- A61P37/04—Immunostimulants
-
- 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
- A61K2039/505—Medicinal preparations containing antigens or antibodies comprising antibodies
-
- 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
-
- 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
Definitions
- This invention relates to adjuvants for vaccines.
- Vaccines are a powerful tool in modern medical practice. They provide an effective, cost-efficient, method of preventing disease, and may also be used to stimulate the immune system in response to an existing infection. Modern vaccines are being developed to ensure enhanced immune responses to infection. Typically, vaccines require co-administration with an adjuvant.
- Adjuvants are stimulants used with specific antigens in vaccine compositions to induce powerful and disease- appropriate immune responses to the vaccine.
- mycobacterial antigens are routinely used to boost cell -mediated immunity as a component of Freund ' s complete adjuvant.
- extracts from Corynehacterium parvurn and Bordetella pertussi s are commonly used.
- T-helper 1 (Thl) cells secrete interleukin 2 (IL-2) and ⁇ -interferon, leading to an activation of cytotoxic T-cells and macrophages .
- T-helper 2 (Th2) cells secrete IL-4 and IL-5, which assist B cells and eosinophils .
- N-acyl homoserine lactones have been isolated from a number of bacteria, such as P otohacterium (Vibrio) fischeri , Pseudomonas aeruingosa, Erwinia carotovora,
- the present invention is based on the realisation that a T-helper 1 (Thl) response to vaccine compositions is not always appropriate, and that a T-helper 2 (Th2) response is preferable m some cases.
- a vaccine composition comprises an active agent (immunogen) and an adjuvant, wherein the adjuvant is capable of reducing T- helper cell type-1 responses and enhancing T-helper cell type-2 responses.
- the adjuvant described above is used m the manufacture of a vaccine composition for the prevention or treatment of infection .
- a homoserine lactone is used m the manufacture of a composition for oral administration with an active agent, to induce oral tolerance to the active agent.
- the adjuvants used m the present invention comprise compounds that are capable of reducing T-helper cell type-1 responses and enhancing T-helper cell type-2 responses. Although specific compounds that have these effects are provided m the specification, it is possible for the skilled person to identify further compounds by testing compounds for the desired effects . With knowledge of an appropriate test, it is possible for the skilled person to use conventional combinatorial chemistry-based approaches to identify further compounds that may have activity m the adjuvant compositions.
- the adjuvants of the invention promote the T-helper 2 response. This may be characterised by measuring IgGl m the presence of the adjuvant of the invention, and comparing this to that obtained using alum or phosphate buffered saline as the adjuvant. The adjuvants also reduce the T-helper 1 response m comparison to that observed for the same immunogen using alum or phosphate buffered saline as the adjuvant.
- the T-helper 1 response may be characterised by measuring IgG2a.
- a preferred embodiment of the invention is the use of N-acyl homoserine lactones (AHL') m the adjuvant compositions.
- AHL' N-acyl homoserine lactones
- OdDHL is most preferred.
- OdDHL suppresses tumour necrosis factor ⁇ (TNF ) and mterleukm-12 (IL-12) production by macrophages, leading to a reduction m Thl cell responses. Further, IgGl and IgE responses, m murine and human tissue cultures, respectively, are promoted.
- TNF tumour necrosis factor ⁇
- IL-12 mterleukm-12
- the adjuvants may be prepared for separate or co- administration with the vaccine.
- the adjuvant and vaccine are co-administered m the one composition.
- the vaccine may be any appropriate vaccine for the treatment/prevention of a particular disease, m particular any disease for which an enhanced Th2 response is desirable.
- the disease is a nematodal infection or a trypanosomal infection, e.g. infection by Necator americanus .
- the vaccine may be prepared by techniques known in the art. Appropriate immunogens will also be known to those skilled in the art. Immunogens may be of any suitable biological material that is capable of eliciting the appropriate immune response.
- the immunogen may be an attenuated microorganism or a protein or peptide fragment of sufficient size to generate the unique immune reaction against an infecting agent.
- the immunogen may be an antibody, e.g.
- Vaccines for hookworm infections are disclosed in Sen et al . , Vaccine, 2000; 18:1096-1102, m Ghosh et al . The Journal of Infectious Diseases, 1999; 180:1674-1681, and in Taylor et al . , J. Exp . Med . , 2000; 191 (8 ): 1429-1436.
- the type and concentrations of the vaccine and the adjuvant may be readily determined by a person skilled in the art.
- the composition may comprise 10 mg/ml of a vaccine and 100 ⁇ M homoserine lactone in the adjuvant, together with a pharmaceutically acceptable diluent.
- concentrations of vaccine will be m the range comprising of 10 mg - 10 ⁇ g/ml
- the adjuvant may be m the range of 10-100 ⁇ M .
- Acceptable diluents will be known to the skilled person, based on conventional adjuvant formulations.
- the vaccine may be administered by any convenient means, m particular, by oral, systemic or parentoral routes, or a combination of these.
- Oral tolerance may therefore be desirable m the present invention m the treatment of autoimmune disorders, where a patient's immune system is attacking self -antigens .
- the administration of a homoserine lactone compound together with autoantigens, via the oral route may induce tolerance to the autoantigens, resulting m reduced severity of the autoimmune disorder.
- the treatment may comprise collagen or myelm proteins as the autoantigen, to treat rheumatoid arthritis and multiple sclerosis, respectively.
- the induction of oral tolerance may be desirable for any protein-based therapy, e.g. antibody therapy.
- the homoserine compounds may therefore induce tolerance to antibodies, thereby enhancing their therapeutic efficacy.
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- Health & Medical Sciences (AREA)
- Immunology (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical & Material Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- Epidemiology (AREA)
- Mycology (AREA)
- Microbiology (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Organic Chemistry (AREA)
- Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
Abstract
Vaccine compositions comprise an adjuvant capable of reducing T-helper cell type-1 responses and enhancing T-helper cell type-2 responses. The adjuvant preferably comprises a homoserine lactone.
Description
ADJUVANTS
Field of the Invention
This invention relates to adjuvants for vaccines. Background of the Invention
Vaccines are a powerful tool in modern medical practice. They provide an effective, cost-efficient, method of preventing disease, and may also be used to stimulate the immune system in response to an existing infection. Modern vaccines are being developed to ensure enhanced immune responses to infection. Typically, vaccines require co-administration with an adjuvant.
Adjuvants are stimulants used with specific antigens in vaccine compositions to induce powerful and disease- appropriate immune responses to the vaccine.
They are often materials derived from bacterial extracts. For example, mycobacterial antigens are routinely used to boost cell -mediated immunity as a component of Freund ' s complete adjuvant. Similarly, extracts from Corynehacterium parvurn and Bordetella pertussi s are commonly used.
Part of the immune response includes a T-helper cell response, of which there are two types. T-helper 1 (Thl) cells secrete interleukin 2 (IL-2) and γ-interferon, leading to an activation of cytotoxic T-cells and macrophages . T-helper 2 (Th2) cells secrete IL-4 and IL-5, which assist B cells and eosinophils .
N-acyl homoserine lactones have been isolated from a number of bacteria, such as P otohacterium (Vibrio) fischeri , Pseudomonas aeruingosa, Erwinia carotovora,
Agrobacterium tumefaciens and others from the Serratia,
Enterobacter and Yersinia genera. The immunogenic effect of one such AHL, N- (3 -oxododecanoyl) -L-homoserine lactone
(OdDHL) , is illustrated in Telford et al , Infection and Immunity, 1998; 66(1): 36-42.
Summary of tne Invention
The present invention is based on the realisation that a T-helper 1 (Thl) response to vaccine compositions is not always appropriate, and that a T-helper 2 (Th2) response is preferable m some cases.
According to the present invention, a vaccine composition comprises an active agent (immunogen) and an adjuvant, wherein the adjuvant is capable of reducing T- helper cell type-1 responses and enhancing T-helper cell type-2 responses.
According to a second aspect of the invention, the adjuvant described above is used m the manufacture of a vaccine composition for the prevention or treatment of infection . According to a third aspect of the invention, a homoserine lactone is used m the manufacture of a composition for oral administration with an active agent, to induce oral tolerance to the active agent. Description of the Invention The adjuvants used m the present invention comprise compounds that are capable of reducing T-helper cell type-1 responses and enhancing T-helper cell type-2 responses. Although specific compounds that have these effects are provided m the specification, it is possible for the skilled person to identify further compounds by testing compounds for the desired effects . With knowledge of an appropriate test, it is possible for the skilled person to use conventional combinatorial chemistry-based approaches to identify further compounds that may have activity m the adjuvant compositions.
The adjuvants of the invention promote the T-helper 2 response. This may be characterised by measuring IgGl m the presence of the adjuvant of the invention, and comparing this to that obtained using alum or phosphate buffered saline as the adjuvant. The adjuvants also reduce the T-helper 1 response m comparison to that observed for the same immunogen using alum or phosphate buffered saline
as the adjuvant. The T-helper 1 response may be characterised by measuring IgG2a.
A preferred embodiment of the invention is the use of N-acyl homoserine lactones (AHL') m the adjuvant compositions. The use of OdDHL is most preferred.
OdDHL suppresses tumour necrosis factor α (TNF ) and mterleukm-12 (IL-12) production by macrophages, leading to a reduction m Thl cell responses. Further, IgGl and IgE responses, m murine and human tissue cultures, respectively, are promoted.
The adjuvants may be prepared for separate or co- administration with the vaccine. Preferably, the adjuvant and vaccine are co-administered m the one composition.
The vaccine may be any appropriate vaccine for the treatment/prevention of a particular disease, m particular any disease for which an enhanced Th2 response is desirable. In a further preferred embodiment, the disease is a nematodal infection or a trypanosomal infection, e.g. infection by Necator americanus . The vaccine may be prepared by techniques known in the art. Appropriate immunogens will also be known to those skilled in the art. Immunogens may be of any suitable biological material that is capable of eliciting the appropriate immune response. The immunogen may be an attenuated microorganism or a protein or peptide fragment of sufficient size to generate the unique immune reaction against an infecting agent. Alternatively, the immunogen may be an antibody, e.g. a monoclonal antibody, raised against an appropriate antigen. Vaccines for hookworm infections are disclosed in Sen et al . , Vaccine, 2000; 18:1096-1102, m Ghosh et al . The Journal of Infectious Diseases, 1999; 180:1674-1681, and in Taylor et al . , J. Exp . Med . , 2000; 191 (8 ): 1429-1436.
The type and concentrations of the vaccine and the adjuvant may be readily determined by a person skilled in the art. For example, the composition may comprise 10 mg/ml of a vaccine and 100 μM homoserine lactone in the
adjuvant, together with a pharmaceutically acceptable diluent. Typically, concentrations of vaccine will be m the range comprising of 10 mg - 10 μg/ml , and the adjuvant may be m the range of 10-100 μM . Acceptable diluents will be known to the skilled person, based on conventional adjuvant formulations.
The vaccine may be administered by any convenient means, m particular, by oral, systemic or parentoral routes, or a combination of these. For example, it is now established that tolerance to the systemic administration of certain drugs may be enhanced by first administering the drug through the oral route. Oral tolerance may therefore be desirable m the present invention m the treatment of autoimmune disorders, where a patient's immune system is attacking self -antigens . In this aspect, the administration of a homoserine lactone compound together with autoantigens, via the oral route, may induce tolerance to the autoantigens, resulting m reduced severity of the autoimmune disorder. For example the treatment may comprise collagen or myelm proteins as the autoantigen, to treat rheumatoid arthritis and multiple sclerosis, respectively. However, the induction of oral tolerance may be desirable for any protein-based therapy, e.g. antibody therapy. The homoserine compounds may therefore induce tolerance to antibodies, thereby enhancing their therapeutic efficacy.
Claims
1. A vaccine composition comprising an active agenc and an adjuvant, wherein the adjuvant is capable of reducing T- helper cell type-1 responses and enhancing T-helper cell type-2 responses.
2. A composition according to claim 1, wherein the adjuvant comprises a homoserine lactone.
3 A composition according to claim 1, wherein the adjuvant comprises N- (3 -oxododecanoyl ) -L-homoserine lactone.
4 A composition according to any preceding claim, for use m therapy.
5. Use of a compound capable of reducing T-helper cell type-1 responses and enhancing T-helper cells type-2 responses as an adjuvant m the manufacture of a vaccine for the prevention or treatment of infection.
6. Use according to claim 5, wherein the vaccine is for the treatment of a nematodal infection or a trypanosomal infection.
7. Use according to claim 5 or claim 6, wherein the compound is a homoserine lactone .
8. Use of a homoserine lactone m the manufacture of a composition for oral administration with an active agent, to induce oral tolerance to the active agent.
9. Use according to claim 8, wherein the active agent is a protein or peptide.
10. Use according to claim 8 or claim 9, wherein the active agent is an autoantigen.
11. Use according to claim 8 or claim 9, wherein the active agent is an antibody.
12. Use according to any of claims 7 to 11, wherein the homoserine lactone is N- (3 -oxododecanoyl ) -L-homoserine lactone .
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| AU33971/01A AU3397101A (en) | 2000-02-25 | 2001-02-26 | Adjuvants |
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| GB0004530.2 | 2000-02-25 | ||
| GBGB0004530.2A GB0004530D0 (en) | 2000-02-25 | 2000-02-25 | Adjuvants |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| WO2001062282A2 true WO2001062282A2 (en) | 2001-08-30 |
| WO2001062282A3 WO2001062282A3 (en) | 2001-12-27 |
Family
ID=9886439
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| PCT/GB2001/000816 WO2001062282A2 (en) | 2000-02-25 | 2001-02-26 | Adjuvants for vaccines |
Country Status (3)
| Country | Link |
|---|---|
| AU (1) | AU3397101A (en) |
| GB (1) | GB0004530D0 (en) |
| WO (1) | WO2001062282A2 (en) |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US7135181B2 (en) | 2000-02-21 | 2006-11-14 | Pharmexa A/S | Method for down-regulation of amyloid |
| EP3299029A1 (en) | 2001-08-20 | 2018-03-28 | H. Lundbeck A/S | Novel method for down-regulation of amyloid |
Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5776974A (en) * | 1993-07-02 | 1998-07-07 | The University Of Nottingham | Immunosuppressant compounds |
-
2000
- 2000-02-25 GB GBGB0004530.2A patent/GB0004530D0/en not_active Ceased
-
2001
- 2001-02-26 AU AU33971/01A patent/AU3397101A/en not_active Abandoned
- 2001-02-26 WO PCT/GB2001/000816 patent/WO2001062282A2/en active Application Filing
Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5776974A (en) * | 1993-07-02 | 1998-07-07 | The University Of Nottingham | Immunosuppressant compounds |
Non-Patent Citations (2)
| Title |
|---|
| SEN L ET AL: "HOOKWORM BURDEN REDUCTIONS IN BALB/C MICE VACCINATED WITH RECOMBINANT ANCYLOSTOMA SECRETED PROTEINS (ASPS) FROM ANCYLOSTOMA DUODENALE, ANCYLOSTOMA CANINUM AND NECATOR AMERICANUS" VACCINE, BUTTERWORTH SCIENTIFIC. GUILDFORD, GB, vol. 18, no. 11/12, January 2000 (2000-01), pages 1096-1102, XP001005230 ISSN: 0264-410X cited in the application * |
| TELFORD G ET AL: "THE PSEUDOMONAS AERUGINOSA QUORUM-SENSING SIGNAL MOLECULE N-(3-OXODODENCANOYL)-L-HOMOSERINE LACTONE HAS IMMUNOMODULATORY ACTIVITY" INFECTION AND IMMUNITY, AMERICAN SOCIETY FOR MICROBIOLOGY. WASHINGTON, US, vol. 66, no. 1, January 1998 (1998-01), pages 36-42, XP001007928 ISSN: 0019-9567 cited in the application * |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US7135181B2 (en) | 2000-02-21 | 2006-11-14 | Pharmexa A/S | Method for down-regulation of amyloid |
| EP3299029A1 (en) | 2001-08-20 | 2018-03-28 | H. Lundbeck A/S | Novel method for down-regulation of amyloid |
Also Published As
| Publication number | Publication date |
|---|---|
| GB0004530D0 (en) | 2000-04-19 |
| WO2001062282A3 (en) | 2001-12-27 |
| AU3397101A (en) | 2001-09-03 |
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