EP1206278A2 - Peptidgemisch und impfstoff gegen eine chronische virale infektion - Google Patents
Peptidgemisch und impfstoff gegen eine chronische virale infektionInfo
- Publication number
- EP1206278A2 EP1206278A2 EP00969241A EP00969241A EP1206278A2 EP 1206278 A2 EP1206278 A2 EP 1206278A2 EP 00969241 A EP00969241 A EP 00969241A EP 00969241 A EP00969241 A EP 00969241A EP 1206278 A2 EP1206278 A2 EP 1206278A2
- Authority
- EP
- European Patent Office
- Prior art keywords
- hepatitis
- virus
- mixture
- peptide
- amino acids
- 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.)
- Withdrawn
Links
- 108090000765 processed proteins & peptides Proteins 0.000 title claims abstract description 87
- 239000000203 mixture Substances 0.000 title claims abstract description 46
- 229960005486 vaccine Drugs 0.000 title claims abstract description 24
- 230000001684 chronic effect Effects 0.000 title abstract description 10
- 230000009385 viral infection Effects 0.000 title abstract description 6
- 208000036142 Viral infection Diseases 0.000 title abstract description 5
- 102000004196 processed proteins & peptides Human genes 0.000 claims abstract description 35
- 101710132601 Capsid protein Proteins 0.000 claims abstract description 32
- 150000001413 amino acids Chemical class 0.000 claims abstract description 24
- 208000002672 hepatitis B Diseases 0.000 claims abstract description 24
- 241000700605 Viruses Species 0.000 claims abstract description 23
- 108010067390 Viral Proteins Proteins 0.000 claims abstract description 17
- 208000037581 Persistent Infection Diseases 0.000 claims abstract description 11
- 108090000623 proteins and genes Proteins 0.000 claims abstract description 10
- 125000003275 alpha amino acid group Chemical group 0.000 claims abstract description 9
- 102000004169 proteins and genes Human genes 0.000 claims abstract description 9
- 208000005176 Hepatitis C Diseases 0.000 claims abstract description 6
- 238000000034 method Methods 0.000 claims abstract description 5
- 241001529453 unidentified herpesvirus Species 0.000 claims abstract description 5
- 239000008194 pharmaceutical composition Substances 0.000 claims abstract description 4
- 239000003085 diluting agent Substances 0.000 claims description 4
- 239000003981 vehicle Substances 0.000 claims description 4
- 239000003814 drug Substances 0.000 claims description 3
- 239000003937 drug carrier Substances 0.000 claims description 3
- 210000001744 T-lymphocyte Anatomy 0.000 abstract description 25
- 210000000612 antigen-presenting cell Anatomy 0.000 abstract description 8
- 230000002163 immunogen Effects 0.000 abstract description 5
- 241000700721 Hepatitis B virus Species 0.000 description 22
- 208000015181 infectious disease Diseases 0.000 description 9
- 241000699670 Mus sp. Species 0.000 description 6
- 239000000427 antigen Substances 0.000 description 6
- 230000004044 response Effects 0.000 description 6
- 108010002350 Interleukin-2 Proteins 0.000 description 5
- 102000036639 antigens Human genes 0.000 description 5
- 108091007433 antigens Proteins 0.000 description 5
- 238000002649 immunization Methods 0.000 description 5
- 230000003612 virological effect Effects 0.000 description 5
- IQFYYKKMVGJFEH-XLPZGREQSA-N Thymidine Chemical compound O=C1NC(=O)C(C)=CN1[C@@H]1O[C@H](CO)[C@@H](O)C1 IQFYYKKMVGJFEH-XLPZGREQSA-N 0.000 description 4
- 230000003053 immunization Effects 0.000 description 4
- 108090000695 Cytokines Proteins 0.000 description 3
- 102000004127 Cytokines Human genes 0.000 description 3
- 108090000790 Enzymes Proteins 0.000 description 3
- 102000004190 Enzymes Human genes 0.000 description 3
- 241000282412 Homo Species 0.000 description 3
- 241000725303 Human immunodeficiency virus Species 0.000 description 3
- 230000005867 T cell response Effects 0.000 description 3
- 210000004027 cell Anatomy 0.000 description 3
- 210000002443 helper t lymphocyte Anatomy 0.000 description 3
- 230000028993 immune response Effects 0.000 description 3
- 238000000338 in vitro Methods 0.000 description 3
- 241000713772 Human immunodeficiency virus 1 Species 0.000 description 2
- 108010071384 Peptide T Proteins 0.000 description 2
- 102000007056 Recombinant Fusion Proteins Human genes 0.000 description 2
- 108010008281 Recombinant Fusion Proteins Proteins 0.000 description 2
- 230000004913 activation Effects 0.000 description 2
- 230000001154 acute effect Effects 0.000 description 2
- 208000037621 acute hepatitis C virus infection Diseases 0.000 description 2
- 239000002671 adjuvant Substances 0.000 description 2
- 230000000840 anti-viral effect Effects 0.000 description 2
- IQFYYKKMVGJFEH-UHFFFAOYSA-N beta-L-thymidine Natural products O=C1NC(=O)C(C)=CN1C1OC(CO)C(O)C1 IQFYYKKMVGJFEH-UHFFFAOYSA-N 0.000 description 2
- 230000005540 biological transmission Effects 0.000 description 2
- 231100000844 hepatocellular carcinoma Toxicity 0.000 description 2
- 206010073071 hepatocellular carcinoma Diseases 0.000 description 2
- 210000001165 lymph node Anatomy 0.000 description 2
- 229940127073 nucleoside analogue Drugs 0.000 description 2
- 230000035755 proliferation Effects 0.000 description 2
- 230000005570 vertical transmission Effects 0.000 description 2
- FWMNVWWHGCHHJJ-SKKKGAJSSA-N 4-amino-1-[(2r)-6-amino-2-[[(2r)-2-[[(2r)-2-[[(2r)-2-amino-3-phenylpropanoyl]amino]-3-phenylpropanoyl]amino]-4-methylpentanoyl]amino]hexanoyl]piperidine-4-carboxylic acid Chemical compound C([C@H](C(=O)N[C@H](CC(C)C)C(=O)N[C@H](CCCCN)C(=O)N1CCC(N)(CC1)C(O)=O)NC(=O)[C@H](N)CC=1C=CC=CC=1)C1=CC=CC=C1 FWMNVWWHGCHHJJ-SKKKGAJSSA-N 0.000 description 1
- DWRXFEITVBNRMK-UHFFFAOYSA-N Beta-D-1-Arabinofuranosylthymine Natural products O=C1NC(=O)C(C)=CN1C1C(O)C(O)C(CO)O1 DWRXFEITVBNRMK-UHFFFAOYSA-N 0.000 description 1
- 108020004705 Codon Proteins 0.000 description 1
- 101710091045 Envelope protein Proteins 0.000 description 1
- 206010016654 Fibrosis Diseases 0.000 description 1
- 241000711549 Hepacivirus C Species 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
- 108090001005 Interleukin-6 Proteins 0.000 description 1
- 206010067125 Liver injury Diseases 0.000 description 1
- 208000001940 Massive Hepatic Necrosis Diseases 0.000 description 1
- 241001529936 Murinae Species 0.000 description 1
- 241000699666 Mus <mouse, genus> Species 0.000 description 1
- 101710144111 Non-structural protein 3 Proteins 0.000 description 1
- 101710188315 Protein X Proteins 0.000 description 1
- 102100021696 Syncytin-1 Human genes 0.000 description 1
- 206010058874 Viraemia Diseases 0.000 description 1
- 229940121357 antivirals Drugs 0.000 description 1
- 238000003556 assay Methods 0.000 description 1
- 230000006399 behavior Effects 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 239000000969 carrier Substances 0.000 description 1
- 238000001516 cell proliferation assay Methods 0.000 description 1
- 239000006285 cell suspension Substances 0.000 description 1
- 229940030156 cell vaccine Drugs 0.000 description 1
- 230000036755 cellular response Effects 0.000 description 1
- 229920002678 cellulose Polymers 0.000 description 1
- 239000001913 cellulose Substances 0.000 description 1
- 231100000749 chronicity Toxicity 0.000 description 1
- 230000007882 cirrhosis Effects 0.000 description 1
- 208000019425 cirrhosis of liver Diseases 0.000 description 1
- 238000002648 combination therapy Methods 0.000 description 1
- 150000001875 compounds Chemical class 0.000 description 1
- 239000012228 culture supernatant Substances 0.000 description 1
- 201000010099 disease Diseases 0.000 description 1
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 229940044627 gamma-interferon Drugs 0.000 description 1
- 231100000753 hepatic injury Toxicity 0.000 description 1
- 230000001900 immune effect Effects 0.000 description 1
- 238000001727 in vivo Methods 0.000 description 1
- 230000003993 interaction Effects 0.000 description 1
- 230000021633 leukocyte mediated immunity Effects 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 210000004185 liver Anatomy 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 238000010172 mouse model Methods 0.000 description 1
- 210000002826 placenta Anatomy 0.000 description 1
- 238000002360 preparation method Methods 0.000 description 1
- 230000037452 priming Effects 0.000 description 1
- 230000003248 secreting effect Effects 0.000 description 1
- 238000013207 serial dilution Methods 0.000 description 1
- 230000001568 sexual effect Effects 0.000 description 1
- 210000000952 spleen Anatomy 0.000 description 1
- 238000010561 standard procedure Methods 0.000 description 1
- 239000006228 supernatant Substances 0.000 description 1
- 230000002459 sustained effect Effects 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 238000002560 therapeutic procedure Methods 0.000 description 1
- 229940104230 thymidine Drugs 0.000 description 1
- 238000011830 transgenic mouse model Methods 0.000 description 1
- 230000029812 viral genome replication Effects 0.000 description 1
Classifications
-
- 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
- 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
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/12—Antivirals
- A61P31/20—Antivirals for DNA viruses
- A61P31/22—Antivirals for DNA viruses for herpes 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
- A61K2039/57—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
- A61K38/00—Medicinal preparations containing 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
- C12N2730/00—Reverse transcribing DNA viruses
- C12N2730/00011—Details
- C12N2730/10011—Hepadnaviridae
- C12N2730/10111—Orthohepadnavirus, e.g. hepatitis B virus
- C12N2730/10122—New viral proteins or individual genes, new structural or functional aspects of known viral proteins or genes
Definitions
- Peptide mixture and vaccine against a chronic viral infection Peptide mixture and vaccine against a chronic viral infection.
- the present invention relates to a peptide mixture and vaccine against a chronic infection caused by a virus, such as hepatitis B, hepatitis C, GB virus-C, HIV and Herpes viruses.
- the peptide mixture is a multiple peptide T helper cell immunogen comprising overlapping peptides spanning the amino acid sequence of a viral protein of the infecting virus.
- the peptide mixture or the vaccine is useful for the treatment of the chronic infection in a patient.
- Background of the invention The CD4+ T helper cell response has been found to be essential in controlling the infection in several chronic viral diseases. Examples are the hepatitis B virus (HBV; Jung M.C.
- HBV hepatitis B virus
- HBV infection is a well documented cause for many types of liver injuries, including cirrhosis and hepatocellular carcinoma (HCC).
- HCC hepatocellular carcinoma
- the major routes for HBV transmission are vertical and sexual. When infected vertically, the infant has a 95% chance of developing a chronic infection whereas, when infected as an adult, the chance for chronicity is less than 5%.
- HBV lifecycle has effectively adopted to the human host by means of vertical transmission.
- HBV surface antigen HBV surface antigen
- HBeAg HBV surface antigen
- HBsAg-specific immune responses are highly effective in preventing HBV infections.
- Vaccines of today are based on the HBsAg and are effective in preventing new HBV infections in both neonates and adults.
- CD4+ T cells In acute and resolving chronic HBV infections activation of HBcAg- and HBeAg-specific, but not HBsAg-specific, CD4+ T cells have been found. These responses are almost never seen during non-resolving chronic HBV infections.
- the HBcAg- and HBeAg-specific CD4+ T cell response in contrast to the HBsAg- specific response, plays a pivotal role in the clearance of HBV infections.
- Nucleoside analogues have recently been introduced as an effective means to reduce the viral load in patients with chronic HBV infections. Almost all treated patients relapse after treatment stop with respect to both liver enzymes and the viral load. In contrast, around 30% of the patients treated with ⁇ -interferon ( ⁇ -IFN) show a permanent response to HBV. Simultaneous with the ⁇ -IFN induced clearance a HBcAg- and HBeAg-specific CD4+ T cell response can be detected.
- nucleoside analogue therapy may be effective in transiently reducing the viral replication additional means to activate the endogenous immune response to HBV proteins are needed to increase the sustained response rate.
- APCs professional antigen presenting cells
- peptides derived from HBcAg have been found to be recognized by specific T cells in murine models.
- the peptide 120-131 primes H-2 S restricted T cells
- peptide 129-140 primes H-2 b restricted T cells
- the peptide 85-96 primes H-2 d restricted T cells
- the peptide 100-120 primes H-2 f restricted T cells (Milich, Immunology Today 9:380-386, 1988).
- immunization of mice with the respective peptide primes T cells that recognize HBcAg digested by APCs.
- these peptides represent true T cell sites.
- No similar immunisation experiments have been performed in humans.
- several peptides (1-25 and 61-85) derived from HBcAg have been found to be recognized by T cells from HBV infected humans (Jung et al., J Virol 69:3358-3368).
- the determining factor for which peptides are to be presented by the host is determined by the MHC HLA genotype of the host.
- Each MHC/HLA molecule can only bind and present one or a few peptides from each viral protein. Subsequently, a T cell vaccine based on one single peptide is limited to only one or a few HLA classes.
- a T cell immunogen or vaccine that would activate virus-specific T cells regardless of the host HLA genotype would be universally useful and most desirable, particularly for the treatment of non-resolving chronic virus infections.
- the present invention is based on a multiple peptide T helper cell immunogen containing a complete viral protein in the form of overlapping synthetic peptides.
- the length of the sequences binding to different HLA class II molecules varies from 10-15 amino acids.
- the present invention is directed to a vaccine against a vaccine against a chronic infection caused by a virus comprising a mixture of 10 to 30 amino acids (aa) long peptides each with a 5 to 25 aa overlap of the adjacent overlapping peptide spanning the amino acid sequence of a viral protein of said virus, and a vehicle.
- the vehicle to be used is selected by the vaccine manufacturer from vehicles accepted for use in human medicaments, and suitable candidates for the selection are provided in e.g. the European or US Pharmacopoeia.
- the invention is also directed to a peptide mixture comprising 10 to 30 amino acids
- the virus is selected from Hepatitis B, Hepatitis C, GB virus-C, HIV and Herpes viruses
- the viral protein is selected from proteins comprising conserved regions. For example, conserved regions are found in hepatitis B core antigen, hepatitis C core antigen and enzyme, GB virus- C enzyme and envelope protein and HIV I core antigens p24 and pi 7.
- the virus is Hepatitis B
- the viral protein is the hepatitis B core antigen.
- the mixture of peptides consists of 15 to 25 amino acids (aa) long peptides each with a 10 to 15 aa overlap of the adjacent overlapping peptide spanning the amino acids 1 to
- the mixture is composed of seventeen 20 to 23 aa long peptides spanning the amino acids 1 to 183 of the hepatitis B core antigen (HBcAg), e.g. seventeen peptides having the amino acid sequences SEQ ID NO: 1 to 17 disclosed in the Sequence listing and in Table 1.
- the invention is further directed to a peptide mixture according to the invention for use as a medicament.
- the invention is additionally directed to a pharmaceutical composition
- a pharmaceutical composition comprising a peptide mixture according to the invention and a pharmaceutically acceptable carrier and/or diluent.
- the pharmaceutically acceptable carrier and/or diluent to be used are/is selected from carriers and/or diluents known to be acceptable for human use, and suitable candidates for the selection are provided in e.g. the European or US Pharmacopoeia.
- the invention is also directed to a method of treating a chronic infection caused by a virus in a patient comprising administering to the patient one or several immunologically effective dosages of a vaccine according to the invention or a peptide mixture according to the invention.
- the virus is Hepatitis B It should be understood that the vaccine, the peptide mixture, or the pharmaceutical composition according to the invention may be used together with other antiviral compounds as combination therapy.
- Table 1 corresponding to the aa sequence of HBcAg sybtype ayw (Galibert et al., 1979, Nature 281:646-648) were synthesized by standard techniques (Sallberg et al., 1991, Immunology Letters 30: 59-68) using an automated synthesizer (Syro, MyltiSynTech, Germany). Preparation of the immunogens and immunizations
- Murine proliferation assays were performed as described previously [Sallberg, 1997 #152; Zhang, 1997 #151]. In brief, 50 ⁇ g recombinant protein was emulsified 1:1 in CFA was injected at 100 ⁇ l doses in groups of 5 -10 mice at the base of the tail. The mice were sacrificed 10 days later and draining lymphnodes were removed. Single cell suspensions were prepared in Clicks media and plated on microtiter plates at 6 x 10 cells per well. Recombinant protein was added in serial dilutions. Supernatant was taken after 24 hours for IL-2 and after 48 hours for IL-4, IL-5, IL-6 and ⁇ -IFN.
- Cytokine concentrations were measured by EIA according to the manual (Endogen, Cambridge, MA). After 72 hours 3H- labeled thymidine (TdR; Amersham) was added, 16 hours later the labeled cells were harvested onto cellulose filters, quenched and the level of 3H-thymidine ([3H]TdR) uptake was determined by liquid scintillation using a beta-counter.
- TdR 3H- labeled thymidine
- mice Groups of five mice were immunized with 200 ⁇ g of the peptide mixture in adjuvant as described. Ten days later the mice were sacrificed, spleens were removed and recall cultures were set. Immunization with the peptide mixture clearly primed H-2b restricted T cells which recognize the previously described T cell site at residues 129-140 previously described (Milich, Immunology Today 9:380-386, 1988). Importantly, the peptide mixture primes T cells which recognize the peptides generated by APC processing and presentation of native like recombinant HBcAg (kindly provided by Dr Darrell Peterson, Commonwealth
- Antigen (peptide no) IL-2 ⁇ lFN ( ⁇ cpm)
- NKA a cell line whose proliferation is proportional to the presence of IL-2 in the culture supernatant. Thus, a sensitive indicator for the presence of IL-2.
- ⁇ cpm the [3H] thymidine uptake determined as counts per minute (cpm) with addition of recall antigens minus the cpm with media alone.
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| SE9903031 | 1999-08-27 | ||
| SE9903031A SE9903031D0 (sv) | 1999-08-27 | 1999-08-27 | Peptide mixture and vaccine against a chronic viral infection |
| PCT/EP2000/008124 WO2001016163A2 (en) | 1999-08-27 | 2000-08-21 | Peptide mixture and vaccine against a chronic viral infection |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| EP1206278A2 true EP1206278A2 (de) | 2002-05-22 |
Family
ID=20416772
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| EP00969241A Withdrawn EP1206278A2 (de) | 1999-08-27 | 2000-08-21 | Peptidgemisch und impfstoff gegen eine chronische virale infektion |
Country Status (5)
| Country | Link |
|---|---|
| EP (1) | EP1206278A2 (de) |
| JP (1) | JP2003508409A (de) |
| AU (1) | AU7903100A (de) |
| SE (1) | SE9903031D0 (de) |
| WO (1) | WO2001016163A2 (de) |
Families Citing this family (15)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| FR2824326B1 (fr) * | 2001-05-04 | 2004-03-19 | Commissariat Energie Atomique | Melange de peptides issus des proteines e6 et/ou e7 de papillomavirus et leurs applications |
| US7351413B2 (en) | 2002-02-21 | 2008-04-01 | Lorantis, Limited | Stabilized HBc chimer particles as immunogens for chronic hepatitis |
| EP1638993A4 (de) * | 2003-06-10 | 2007-05-09 | Univ Melbourne | Immunmodulierende zusammensetzungen, anwendungen davon und verfahren zu deren herstellung |
| GB0608368D0 (en) * | 2006-04-28 | 2006-06-07 | Isis Innovation | Process for making Oligopeptides |
| RU2490024C2 (ru) | 2006-06-28 | 2013-08-20 | Статенс Серум Инститьют | Расширение спектра т клеток для включения субдоминантных эпитопов путем вакцинации с антигенами, доставленными как белковые фрагменты или пептидные коктейли |
| US9481912B2 (en) | 2006-09-12 | 2016-11-01 | Longhorn Vaccines And Diagnostics, Llc | Compositions and methods for detecting and identifying nucleic acid sequences in biological samples |
| US8097419B2 (en) | 2006-09-12 | 2012-01-17 | Longhorn Vaccines & Diagnostics Llc | Compositions and method for rapid, real-time detection of influenza A virus (H1N1) swine 2009 |
| US8080645B2 (en) | 2007-10-01 | 2011-12-20 | Longhorn Vaccines & Diagnostics Llc | Biological specimen collection/transport compositions and methods |
| US11041215B2 (en) | 2007-08-24 | 2021-06-22 | Longhorn Vaccines And Diagnostics, Llc | PCR ready compositions and methods for detecting and identifying nucleic acid sequences |
| WO2009029686A1 (en) * | 2007-08-27 | 2009-03-05 | Longhorn Vaccines & Diagnostics Llc | Immunogenic compositions and methods |
| US10004799B2 (en) | 2007-08-27 | 2018-06-26 | Longhorn Vaccines And Diagnostics, Llc | Composite antigenic sequences and vaccines |
| EP2106803A1 (de) | 2008-04-04 | 2009-10-07 | Fondazione Centro San Raffaele del Monte Tabor | Verfahren zum Entwurf von sich überlappenden Peptiden und Verwendungen der Peptide zur Messung von T-Zell Antworten in HIV Patienten |
| CN102060929A (zh) * | 2010-06-07 | 2011-05-18 | 夏书奇 | T细胞免疫平衡肽 |
| US10286050B2 (en) * | 2013-12-13 | 2019-05-14 | The United States Of America, As Represented By The Secretary, Department Of Health And Human Services | Multi-epitope TARP peptide vaccine and uses thereof |
| WO2020247858A1 (en) * | 2019-06-07 | 2020-12-10 | Oregon Health & Science University | Hepatitis b virus-specific t cell responses |
Family Cites Families (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB9201139D0 (en) * | 1992-01-20 | 1992-03-11 | Connaught Lab | Synthetic peptides for a rubella vaccine |
| NZ299048A (en) * | 1992-03-06 | 1998-09-24 | Innogenetics Sa Nv | Modified peptides corresponding to immunologically useful epitopes in hiv, hcv and htlv and their use especially when biotinylated |
| WO1996022067A2 (en) * | 1994-12-27 | 1996-07-25 | United Biomedical, Inc. | Peptide ratchet libraries for ctl-inducing vaccines and therapeutics |
-
1999
- 1999-08-27 SE SE9903031A patent/SE9903031D0/xx unknown
-
2000
- 2000-08-21 AU AU79031/00A patent/AU7903100A/en not_active Abandoned
- 2000-08-21 WO PCT/EP2000/008124 patent/WO2001016163A2/en not_active Application Discontinuation
- 2000-08-21 EP EP00969241A patent/EP1206278A2/de not_active Withdrawn
- 2000-08-21 JP JP2001519724A patent/JP2003508409A/ja active Pending
Non-Patent Citations (1)
| Title |
|---|
| See references of WO0116163A2 * |
Also Published As
| Publication number | Publication date |
|---|---|
| WO2001016163A2 (en) | 2001-03-08 |
| SE9903031D0 (sv) | 1999-08-27 |
| JP2003508409A (ja) | 2003-03-04 |
| WO2001016163A3 (en) | 2001-09-07 |
| AU7903100A (en) | 2001-03-26 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| Mizukoshi et al. | Cellular immune responses to the hepatitis B virus polymerase | |
| Locarnini et al. | The hepatitis B virus and common mutants | |
| US7763589B2 (en) | Compositions and methods for treating intracellular diseases | |
| WO2001016163A2 (en) | Peptide mixture and vaccine against a chronic viral infection | |
| JP3857305B2 (ja) | 慢性ウイルス性肝臓病に対する治療薬として用いる組成物 | |
| US7368118B2 (en) | Peptides for inducing cytotoxic T lymphocyte responses to hepatitis B virus | |
| Murray et al. | Protective immunisation against hepatitis B with an internal antigen of the virus | |
| US20110263822A1 (en) | Composition for the prophylaxis and treatment of hbv infections and hbv-mediated diseases | |
| EP1375511B1 (de) | Peptide zum Induzieren einer Antwort der zytotoxischen T-Lymphozyten gerichtet gegen das Hepatitis-B-Virus | |
| US6297048B1 (en) | Hepatitis therapeutics | |
| EP0534618B1 (de) | Peptide, die die zytotoxische T-Lymphozyte Antwort gegen Hepatitis-B-Virus induzieren | |
| EP0625204B1 (de) | Hepatistherapeutikum | |
| US5840303A (en) | Peptides for inducing cytotoxic T lymphocyte responses to hepatitis B virus | |
| ES2393963T3 (es) | Expresión de HBcAg y utilizaciones terapéuticas y de diagnóstico | |
| CA2156416C (en) | Peptides for inducing cytotoxic t lymphocyte responses to hepatitis b virus | |
| Harrison | Genetic variants of HBV | |
| Gerlich | Giessen | |
| Murray et al. | S.) zyxwvutsrqpo | |
| Harrison et al. | Hepatitis B virus and hepatitis delta virus |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PUAI | Public reference made under article 153(3) epc to a published international application that has entered the european phase |
Free format text: ORIGINAL CODE: 0009012 |
|
| 17P | Request for examination filed |
Effective date: 20020225 |
|
| AX | Request for extension of the european patent |
Free format text: AL;LT;LV;MK;RO;SI |
|
| 17Q | First examination report despatched |
Effective date: 20030702 |
|
| STAA | Information on the status of an ep patent application or granted ep patent |
Free format text: STATUS: THE APPLICATION IS DEEMED TO BE WITHDRAWN |
|
| 18D | Application deemed to be withdrawn |
Effective date: 20031113 |