AU619826B2 - A synthetic vaccine against foot and mouth disease and a process for the preparation thereof - Google Patents
A synthetic vaccine against foot and mouth disease and a process for the preparation thereof Download PDFInfo
- Publication number
- AU619826B2 AU619826B2 AU33265/89A AU3326589A AU619826B2 AU 619826 B2 AU619826 B2 AU 619826B2 AU 33265/89 A AU33265/89 A AU 33265/89A AU 3326589 A AU3326589 A AU 3326589A AU 619826 B2 AU619826 B2 AU 619826B2
- Authority
- AU
- Australia
- Prior art keywords
- membrane
- synthetic vaccine
- mouth disease
- foot
- vaccine
- 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.)
- Ceased
Links
- 241000710198 Foot-and-mouth disease virus Species 0.000 title claims description 36
- 229940126577 synthetic vaccine Drugs 0.000 title claims description 22
- 208000007212 Foot-and-Mouth Disease Diseases 0.000 title claims description 15
- 238000000034 method Methods 0.000 title claims description 12
- 238000002360 preparation method Methods 0.000 title claims description 9
- 150000001875 compounds Chemical class 0.000 claims description 34
- 238000004873 anchoring Methods 0.000 claims description 31
- 229960005486 vaccine Drugs 0.000 claims description 19
- 239000000203 mixture Substances 0.000 claims description 17
- 108090000765 processed proteins & peptides Proteins 0.000 claims description 12
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 10
- 102000004169 proteins and genes Human genes 0.000 claims description 8
- 108090000623 proteins and genes Proteins 0.000 claims description 8
- 102000004196 processed proteins & peptides Human genes 0.000 claims description 7
- 241000700605 Viruses Species 0.000 claims description 6
- 230000021615 conjugation Effects 0.000 claims description 6
- 239000012528 membrane Substances 0.000 claims description 6
- 125000000217 alkyl group Chemical group 0.000 claims description 5
- 125000004432 carbon atom Chemical group C* 0.000 claims description 4
- 239000000969 carrier Substances 0.000 claims description 4
- 238000009472 formulation Methods 0.000 claims description 4
- 102000004895 Lipoproteins Human genes 0.000 claims description 3
- 108090001030 Lipoproteins Proteins 0.000 claims description 3
- 239000002671 adjuvant Substances 0.000 claims description 3
- 150000001413 amino acids Chemical class 0.000 claims description 3
- 238000006243 chemical reaction Methods 0.000 claims description 3
- 101710132601 Capsid protein Proteins 0.000 claims description 2
- 101710197658 Capsid protein VP1 Proteins 0.000 claims description 2
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 2
- 241000124008 Mammalia Species 0.000 claims description 2
- 101710118046 RNA-directed RNA polymerase Proteins 0.000 claims description 2
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims description 2
- 101710108545 Viral protein 1 Proteins 0.000 claims description 2
- 125000002252 acyl group Chemical group 0.000 claims description 2
- 125000003342 alkenyl group Chemical group 0.000 claims description 2
- 125000000304 alkynyl group Chemical group 0.000 claims description 2
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 2
- 230000001580 bacterial effect Effects 0.000 claims description 2
- 210000004899 c-terminal region Anatomy 0.000 claims description 2
- 229910052799 carbon Inorganic materials 0.000 claims description 2
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 2
- 229910052739 hydrogen Inorganic materials 0.000 claims description 2
- 239000001257 hydrogen Substances 0.000 claims description 2
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 2
- 125000004043 oxo group Chemical group O=* 0.000 claims description 2
- 229910052760 oxygen Inorganic materials 0.000 claims description 2
- 239000001301 oxygen Substances 0.000 claims description 2
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 2
- 229910052717 sulfur Inorganic materials 0.000 claims description 2
- 239000011593 sulfur Substances 0.000 claims description 2
- 239000003643 water by type Substances 0.000 claims description 2
- 101900061472 Foot-and-mouth disease virus Capsid protein VP1 Proteins 0.000 claims 1
- 208000030194 mouth disease Diseases 0.000 claims 1
- 229960005030 other vaccine in atc Drugs 0.000 claims 1
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 9
- 241001465754 Metazoa Species 0.000 description 9
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 6
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 6
- 239000011347 resin Substances 0.000 description 6
- 229920005989 resin Polymers 0.000 description 6
- SECXISVLQFMRJM-UHFFFAOYSA-N N-Methylpyrrolidone Chemical compound CN1CCCC1=O SECXISVLQFMRJM-UHFFFAOYSA-N 0.000 description 5
- 239000013543 active substance Substances 0.000 description 5
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 5
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 4
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 4
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 4
- WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 3
- 108010028921 Lipopeptides Proteins 0.000 description 3
- SJRJJKPEHAURKC-UHFFFAOYSA-N N-Methylmorpholine Chemical compound CN1CCOCC1 SJRJJKPEHAURKC-UHFFFAOYSA-N 0.000 description 3
- DKGAVHZHDRPRBM-UHFFFAOYSA-N Tert-Butanol Chemical compound CC(C)(C)O DKGAVHZHDRPRBM-UHFFFAOYSA-N 0.000 description 3
- 230000015572 biosynthetic process Effects 0.000 description 3
- 230000008878 coupling Effects 0.000 description 3
- 238000010168 coupling process Methods 0.000 description 3
- 238000005859 coupling reaction Methods 0.000 description 3
- UAOMVDZJSHZZME-UHFFFAOYSA-N diisopropylamine Chemical compound CC(C)NC(C)C UAOMVDZJSHZZME-UHFFFAOYSA-N 0.000 description 3
- 230000000694 effects Effects 0.000 description 3
- 238000000926 separation method Methods 0.000 description 3
- HVCNXQOWACZAFN-UHFFFAOYSA-N 4-ethylmorpholine Chemical compound CCN1CCOCC1 HVCNXQOWACZAFN-UHFFFAOYSA-N 0.000 description 2
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 2
- YNJBLTDKTMKEET-ZLUOBGJFSA-N Cys-Ser-Ser Chemical compound SC[C@H](N)C(=O)N[C@@H](CO)C(=O)N[C@@H](CO)C(O)=O YNJBLTDKTMKEET-ZLUOBGJFSA-N 0.000 description 2
- NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 description 2
- 238000004458 analytical method Methods 0.000 description 2
- 210000004027 cell Anatomy 0.000 description 2
- IJKVHSBPTUYDLN-UHFFFAOYSA-N dihydroxy(oxo)silane Chemical compound O[Si](O)=O IJKVHSBPTUYDLN-UHFFFAOYSA-N 0.000 description 2
- 238000002649 immunization Methods 0.000 description 2
- 230000003053 immunization Effects 0.000 description 2
- 230000003472 neutralizing effect Effects 0.000 description 2
- 239000012071 phase Substances 0.000 description 2
- 239000008363 phosphate buffer Substances 0.000 description 2
- 239000002904 solvent Substances 0.000 description 2
- 238000003786 synthesis reaction Methods 0.000 description 2
- UMRUUWFGLGNQLI-QFIPXVFZSA-N (2s)-2-(9h-fluoren-9-ylmethoxycarbonylamino)-6-[(2-methylpropan-2-yl)oxycarbonylamino]hexanoic acid Chemical compound C1=CC=C2C(COC(=O)N[C@@H](CCCCNC(=O)OC(C)(C)C)C(O)=O)C3=CC=CC=C3C2=C1 UMRUUWFGLGNQLI-QFIPXVFZSA-N 0.000 description 1
- VVQIIIAZJXTLRE-QMMMGPOBSA-N (2s)-2-amino-6-[(2-methylpropan-2-yl)oxycarbonylamino]hexanoic acid Chemical compound CC(C)(C)OC(=O)NCCCC[C@H](N)C(O)=O VVQIIIAZJXTLRE-QMMMGPOBSA-N 0.000 description 1
- NKUHWWPUOXOIIR-CRCLSJGQSA-N (4r)-5-amino-4-[[(2s)-2-azaniumylpropanoyl]amino]-5-oxopentanoate Chemical compound C[C@H](N)C(=O)N[C@@H](C(N)=O)CCC(O)=O NKUHWWPUOXOIIR-CRCLSJGQSA-N 0.000 description 1
- 125000003088 (fluoren-9-ylmethoxy)carbonyl group Chemical group 0.000 description 1
- BDNKZNFMNDZQMI-UHFFFAOYSA-N 1,3-diisopropylcarbodiimide Chemical compound CC(C)N=C=NC(C)C BDNKZNFMNDZQMI-UHFFFAOYSA-N 0.000 description 1
- ASOKPJOREAFHNY-UHFFFAOYSA-N 1-Hydroxybenzotriazole Chemical compound C1=CC=C2N(O)N=NC2=C1 ASOKPJOREAFHNY-UHFFFAOYSA-N 0.000 description 1
- BWMMKQPATDUYKB-IHRRRGAJSA-N Arg-Tyr-Asn Chemical compound NC(N)=NCCC[C@H](N)C(=O)N[C@H](C(=O)N[C@@H](CC(N)=O)C(O)=O)CC1=CC=C(O)C=C1 BWMMKQPATDUYKB-IHRRRGAJSA-N 0.000 description 1
- IYVSIZAXNLOKFQ-BYULHYEWSA-N Asn-Asp-Val Chemical compound [H]N[C@@H](CC(N)=O)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](C(C)C)C(O)=O IYVSIZAXNLOKFQ-BYULHYEWSA-N 0.000 description 1
- 241000283690 Bos taurus Species 0.000 description 1
- 241000700198 Cavia Species 0.000 description 1
- 241000700199 Cavia porcellus Species 0.000 description 1
- 241000699800 Cricetinae Species 0.000 description 1
- BWGNESOTFCXPMA-UHFFFAOYSA-N Dihydrogen disulfide Chemical compound SS BWGNESOTFCXPMA-UHFFFAOYSA-N 0.000 description 1
- 238000002965 ELISA Methods 0.000 description 1
- KDXKERNSBIXSRK-UHFFFAOYSA-N Lysine Natural products NCCCCC(N)C(O)=O KDXKERNSBIXSRK-UHFFFAOYSA-N 0.000 description 1
- 239000004472 Lysine Substances 0.000 description 1
- AWJGUZSYVIVZGP-YUMQZZPRSA-N Pro-Val Chemical compound CC(C)[C@@H](C(O)=O)NC(=O)[C@@H]1CCCN1 AWJGUZSYVIVZGP-YUMQZZPRSA-N 0.000 description 1
- 238000012300 Sequence Analysis Methods 0.000 description 1
- NLQUOHDCLSFABG-GUBZILKMSA-N Ser-Arg-Arg Chemical compound NC(N)=NCCC[C@H](NC(=O)[C@H](CO)N)C(=O)N[C@@H](CCCN=C(N)N)C(O)=O NLQUOHDCLSFABG-GUBZILKMSA-N 0.000 description 1
- 241000282887 Suidae Species 0.000 description 1
- RHQDFWAXVIIEBN-UHFFFAOYSA-N Trifluoroethanol Chemical compound OCC(F)(F)F RHQDFWAXVIIEBN-UHFFFAOYSA-N 0.000 description 1
- 108010067390 Viral Proteins Proteins 0.000 description 1
- 239000002253 acid Substances 0.000 description 1
- 238000007792 addition Methods 0.000 description 1
- 125000003277 amino group Chemical group 0.000 description 1
- 230000002788 anti-peptide Effects 0.000 description 1
- 230000000903 blocking effect Effects 0.000 description 1
- 238000009395 breeding Methods 0.000 description 1
- 230000001488 breeding effect Effects 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- 238000004587 chromatography analysis Methods 0.000 description 1
- 238000003776 cleavage reaction Methods 0.000 description 1
- 238000009833 condensation Methods 0.000 description 1
- 230000005494 condensation Effects 0.000 description 1
- 229940028617 conventional vaccine Drugs 0.000 description 1
- 238000001816 cooling Methods 0.000 description 1
- 238000000502 dialysis Methods 0.000 description 1
- 229940043279 diisopropylamine Drugs 0.000 description 1
- BGRWYRAHAFMIBJ-UHFFFAOYSA-N diisopropylcarbodiimide Natural products CC(C)NC(=O)NC(C)C BGRWYRAHAFMIBJ-UHFFFAOYSA-N 0.000 description 1
- 238000010790 dilution Methods 0.000 description 1
- 239000012895 dilution Substances 0.000 description 1
- 239000000839 emulsion Substances 0.000 description 1
- 239000000706 filtrate Substances 0.000 description 1
- 238000010438 heat treatment Methods 0.000 description 1
- 238000004128 high performance liquid chromatography Methods 0.000 description 1
- 239000012456 homogeneous solution Substances 0.000 description 1
- 230000002779 inactivation Effects 0.000 description 1
- 208000015181 infectious disease Diseases 0.000 description 1
- 238000011081 inoculation Methods 0.000 description 1
- 210000003734 kidney Anatomy 0.000 description 1
- 230000003902 lesion Effects 0.000 description 1
- 125000003588 lysine group Chemical group [H]N([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])(N([H])[H])C(*)=O 0.000 description 1
- 125000000325 methylidene group Chemical group [H]C([H])=* 0.000 description 1
- 150000007530 organic bases Chemical class 0.000 description 1
- 230000003647 oxidation Effects 0.000 description 1
- 238000007254 oxidation reaction Methods 0.000 description 1
- 238000010647 peptide synthesis reaction Methods 0.000 description 1
- 108010053725 prolylvaline Proteins 0.000 description 1
- 125000006239 protecting group Chemical group 0.000 description 1
- 238000000746 purification Methods 0.000 description 1
- 238000001953 recrystallisation Methods 0.000 description 1
- 102220006727 rs113994181 Human genes 0.000 description 1
- 230000007017 scission Effects 0.000 description 1
- KKNIUBFRGPFELP-UHFFFAOYSA-N secretolin Chemical compound N=1C=CNC=1CC(N)C(=O)NC(CO)C(=O)NC(CC(O)=O)C(=O)NCC(=O)NC(C(C)O)C(=O)NC(C(=O)NC(C(=O)NC(CO)C(=O)NC(CCC(O)=O)C(=O)NC(CC(C)C)C(=O)NC(CO)C(=O)NC(CCCNC(N)=N)C(=O)NC(CC(C)C)C(=O)NC(CCCNC(N)=N)C(=O)NC(CC(O)=O)C(=O)NC(CO)C(=O)NC(C)C(=O)NC(CCCNC(N)=N)C(=O)NC(CC(C)C)C(=O)NC(CCC(N)=O)C(=O)NC(CCCNC(N)=N)C(=O)NC(CC(C)C)C(=O)NC(CC(C)C)C(=O)NC(CCC(N)=O)C(=O)NCC(=O)NC(CC(C)C)C(=O)NC(C(C)C)C(O)=O)C(C)O)CC1=CC=CC=C1 KKNIUBFRGPFELP-UHFFFAOYSA-N 0.000 description 1
- 239000013049 sediment Substances 0.000 description 1
- 125000003607 serino group Chemical group [H]N([H])[C@]([H])(C(=O)[*])C(O[H])([H])[H] 0.000 description 1
- XZKQVQKUZMAADP-UHFFFAOYSA-N serinyl-serine Chemical compound OCC(N)C(=O)NC(CO)C(O)=O XZKQVQKUZMAADP-UHFFFAOYSA-N 0.000 description 1
- 210000002966 serum Anatomy 0.000 description 1
- 239000002356 single layer Substances 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 239000007790 solid phase Substances 0.000 description 1
- 239000000243 solution Substances 0.000 description 1
- 238000000527 sonication Methods 0.000 description 1
- 241000894007 species Species 0.000 description 1
- 238000010186 staining Methods 0.000 description 1
- 238000003756 stirring Methods 0.000 description 1
- 238000010254 subcutaneous injection Methods 0.000 description 1
- 239000007929 subcutaneous injection Substances 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 238000006467 substitution reaction Methods 0.000 description 1
- 125000004213 tert-butoxy group Chemical group [H]C([H])([H])C(O*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- HNKJADCVZUBCPG-UHFFFAOYSA-N thioanisole Chemical compound CSC1=CC=CC=C1 HNKJADCVZUBCPG-UHFFFAOYSA-N 0.000 description 1
- 238000002255 vaccination Methods 0.000 description 1
- 238000005406 washing Methods 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
- A61P37/00—Drugs for immunological or allergic disorders
-
- 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
- C12N2770/00—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA ssRNA viruses positive-sense
- C12N2770/00011—Details
- C12N2770/32011—Picornaviridae
- C12N2770/32111—Aphthovirus, e.g. footandmouth disease virus
- C12N2770/32122—New viral proteins or individual genes, new structural or functional aspects of known viral proteins or genes
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Organic Chemistry (AREA)
- Medicinal Chemistry (AREA)
- General Health & Medical Sciences (AREA)
- Biophysics (AREA)
- General Chemical & Material Sciences (AREA)
- Genetics & Genomics (AREA)
- Gastroenterology & Hepatology (AREA)
- Molecular Biology (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Virology (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Immunology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Biochemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
- Peptides Or Proteins (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Medicinal Preparation (AREA)
Description
Form COMMONWEALTH OF AUSTRALIA PATENTS ACT 1952-69 COMPLETE SPECIFICATION
(ORIGINAL)
Class Int. Class Application Number: Lodged: Complete Specification Lodged: Accepted: Published: Priority: o Rdig.ed Art: 0 0 I o HOECHST AKTIENGESELLSCHAFT bJame of Applicant: Address of Applicant: 0 Actual Inventor: 'Address for Service: 0 50 Bruningstrasse, D-6230 Frankfurt/Main Republic of Germany 80, Federal KARL-HEINZ WIESMULLER, GUNTER HESS and GUNTHER JUNG EDWD. WATERS SONS, 50 QUEEN STREET, MELBOURNE, AUSTRALIA, 3000.
Complete Specification for the invention entitled: A SYNTHETIC VACCINE AGAINST FOOT AND MOUTH DISEASE AND A PROCESS FOR THE PREPARATION THEREOF The following statement is a full description of this invention, including the best method of performing it known to 1.
VI
HOECHST AKTIENGESELLSCHAFT HOE 88/F 091 Dr. WN/rh Description A synthetic vaccine against foot and mouth disease and a process for the preparation thereof The present invention relates to a vaccine against foot and mouth disease and a process for the preparation thereof.
Foot and mouth disease (FMD) causes great losses 4n cattle breeding, despite vaccines which have now been available for a long time. One reason for the occurrence of foot and mouth disease at present is the unreliability of classical vaccines which contain killed or inactivated o O* FMD viruses: the inactivation of the virus is occasioni .O ally incomplete so that "post-vaccination" outbreaks of FMD may occur (cf. Bbhm, Strohmaier, Tierarztl. Umschau 39, 3 8 (1984)). This danger does not exist with 00 Os j o synthetic FMD vaccines because in the latter only partial 0 0 sequences of certain viral proteins, which do not have the function of an intact virus, are used.
120 Although synthetic FMD vaccines already exist (cf.
European Patent Application 0,204,480) they are still in need of improvement.
It has now been found that particularly effective FMD vaccines can be prepared using membrane-anchoring compounds and certain partial sequences of the FMD virus.
I Although the preparation of synthetic vaccines is mentioned in German Offenlegungsschrift DE 3,546,150 Al as one of many possible uses of membrane anchor/active substance conjugates, it was not to be expected that the conjugates of membrane-anchoring compounds and partial sequences of the FMD virus (membrane anchor/active substance conjugates) would exhibit the exceptional activity which has been found on administration of relatively small amounts of vaccine.
2 Furthermore, the said vaccines are distinguished, surprisingly, by providing an adequate protection even after a single administration of the vaccine. Moreover, they have the advantage by comparison with conventional vaccines that virtually unliimited storage without cooling is possible.
Accordingly, the invention relates to a synthetic vaccine against foot and mouth disease, which vaccine comprises a conjugate of at least one membrane-anchoring compound and at least one partial sequence of a protein of the foot and mouth disease virus.
0 0 900 0 0 00 00 00 0000 00 0 O 0 S15 00 00 0 0 0 o0 0 0 0 0 0 0000 0 0 00 0 0 00 *0o2 0 0 0 0 125 0* Membrane-anchoring compounds are compounds which can be embedded in biological or synthetic membranes.
Further information on membrane-anchoring compounds is to be found in the German Offenlegungsschrift 3,546,150 already cited and in G. Jung et al. in "Peptides, Structure and Function", V.J. Hruby and D.H. Rich, pages 179 to 182, Pierce Chem. Co. Rockford, Illinois, (1983).
Preferred membrane anchor/active substance conjugates are those in which a membrane-anchoring compound and an active substance, i.e. a partial sequence of an FMD virus, are linked together covalently.
Particularly suitable membrane anchor/active substance conjugates have proven to be those in which the membraneanchoring compound is a lipoprotein. Very particularly suitable are membrane-anchoring compounds of the following formulae R -CO-0-CH 2 R'-CO-0-CH*
I
(CH2n
(IH
2 )n
A
R"-CO-NH-CH*-CO-X
R -CO-NH-CH*-CO-X R -O-CH 2 R'-0-6H* (CH2n
H
2 )n
A
(IH
2)m
R"-CO-NH-CH*-CO-X
R -O-CO-OH 2 R'-0-CO-CH* A (CH 2 )m H (CH2
R"-CO-NH-CH*-CO-X
II. III, -3 R -CO-CH 2
B
1 -C 0-OH.
R -Nil-CO-CH R' -NH-CO-OH (OH)n (dH2) B A A A (CH (OH 2 (Cm R"-CO-NH-CH -CO-X R"-CO-NH-CH -OO-X B"-NH-OO-OH -O-X IV. V. VI.
B-CmI 1 2 B -CH*
(CH
o A 4 0 (O B -CC- N H 000 'a 00
VI
0 0 a 0 O 0 0 0 a0 a00 in whi4ch A can be sulfur, oxygen, disulfide methylene (-CH 2 or -NH-; n =0 to 5, m 1 or 2; C* is an asymmetric carbon atom with the R~ or S conf ig-uration, R, R' and R" are identical or different and each is hydrogen or an alkyl, alkenyl or alkynyl group which has 7 to 25 carbon atoms and which can be substituted by hydroxyl, amino, oxo, acyl, alkyl or cycloalkyl groups, B in formula VI can have the meaning of each of the
-(CH
2 )n-(substituted alkyl) radicals listed in formulae I-V, and RI and R 2 are identical or different and have the same meanings as R, R' and R" but can also be -OR, -O-COR, -COOR, NHCOR or -CONHR, where X is a chain of 1 to 10 amino acids to which the partial sequence of the virus is bonded.
Examples of these to be particularly emphasized are: N-termini occuring in bacterial lipoprotein, such as, for example: Y-Ser-Ser-Ser-Asn, Y-Ile-Leu-Leu-Ala, Y-Ala-Asn- Asn-Gln, Y-Asn-Ser-Asn-Ser, Y-Gly-Ala-Met-Ser, Y-Gln-Ala- Asn-Tyr, Y-Gln-Val-Asn-Asn, Y-Asp-Asn-Ser-Ser, where Y can be one of the radicals listed under formula I to VII.
15 These lipopentapeptides can also be used in shortened ,t form (lipodi, lipotri or lipotetrapeptides) as membranei anchoring compound. Very particularly preferred is Npalmitoyl-S-[2,3-(bispalmitoyloxy)propyl]-cysteinyl- S, seryl-serine (Pam 3 Cys-Ser-Ser), N-palmitoyl-S-[2,3-(bis- 0 a palmitoyloxy)propyl]-cysteinyl-seryl-glycine and Npalmitoyl-S-[2,3-(bispalmitoyloxy)propyl]-cysteinylo @09a alanyl-D-isoglutamine. Examples of other preferred membrane-anchoring compounds are to be found in German Offenlegungsschrift 3,546,150.
Many different partial sequences can be employed as the partial sequences of the FMD virus which are bonded to o.oa the membrane-anchoring compound. The following partial 04 sequences are preferred: SPartial sequence -(134-154) -(135-154) -(134-158) -(134-160) -(141-160) -(141-158) -(200-213) -(200-210) -(161-180) it being possible to use the sequences of all known ili:ii serotypes and subtypes. Examples of serotypes which may be indicated in this connection are: Serotype A:
A
5 Westerwald 134 160 NKYSTGGP RRGDMGSAAARAAI(QLP 161 180 ASFNYGAI HAlTIHELLVRM 200 213 RHKQKI IAPARQLL
A
12 'USA 134 160
NKYSASGSG-VRGDFGSLAPRVARQLP
161 180
ASFNYGAIKAETIHELLVRM
200 212 RHKQKI IAPGKQL 0 00a 000 06 0 06) 00 0 0 0 0 Serotype C: C3. Oberbayern 134 160 TTY TAST RGDLAHLTAT RAGHLP 161 180 TSFNFGAUXAETI TGLLVAM 200 213
RHKQPLVAPAKQLL
060 0v~fl 0 0gC.~J 66 0 0 00 o 0 0 6 06 00CC 0 066060 0 0 006 o25 0 00 Serotype 0: 01 Xauf beuren 01 Lausanne 02 Normandy 0 Wuppertal 0 Israel 01 Kaufbeuren 01 Kaufbeuren 134
CRYNRNAVPNLRGDLQVLAQKVARTLP
CRYSRNAVPNLRGDLQVLAQKVARTLP
RRYSRI4AVPNVRGDLQALGQKARTLP CLYSDARVSNVRGDLQVLAQKAERALj
CRYGNVAVTNVRGDLQVLAQKAERAILP
200 213
RHKQKIVAPVKQTL
161 180
TSFNYGAIKATRVTELLYRM
160 Particularly suitable synthetic vaccines are those which are composed of a mixture of peptides from various sero- 6 and/or subtypes of the foot and mouth disease virus, each of which is covalently bonded to the membrane-anchoring compound(s).
Particularly preferred synthetic vaccines are those which are composed of a mixture of sequences VP1 134-160 of serotypes 0, A and C, bonded to the membrane-anchoring compound N-palmitoyl-S-[2,3-(bispalmitoyloxy)propyl]cysteinyl-seryl-serine.
When the sequence 134-154 from serotype 0 and the sequence 134-155 from serotype A are used, the latter can, as long as it contains C-terminal lysine, be linked covalently via the e-amino group to the membrane-anchoring compound.
C P Particularly suitable synthetic vaccines according to the invention have proven to be those which contain the partial sequence of FMD virus VP 1 (135-154).
Additionally particularly preferred is a vaccine composed of N-palmitoyl-S-[2,3-(bispalmitoyloxy)propyl]-cysteinyl- Sseryl-seryl-VP 1 (135-154), i.e. the compound of the 20 formula below.
S°135 ArgTyr Asn'A Asn Asp Val T h Ala 0*0 t: (Asn Gy Leu tp o I pro Val li Ser Arg Arg l s Co0
A
la
CH
2
-CH-CH
2
CH
2
-CH
6 0 N H Gin C- C:O 0-C .s 7 The membrane-anchoring compounds can, in principle, be in the form of R,S or R,R diastereomers or of a mixture of diastereomers. However, it has emerged that the vaccines which contain a R,R-diastereomeric membrane-anchoring compound have particularly high activity.
The invention additionally relates to a process for the preparation of a synthetic vaccine, which comprises bonding partial sequences of the FMD virus by a conjugation reaction to the membrane-anchoring compound. The conjugation reaction can be, for example, a condensation, addition, substitution, oxidation or disulfide formation, Preferred conjugation methods are indicated in Example 1.
Further conjugation methods are described in German Offenlegungsschrift 3,546,150 which has already been *o .'15 cited.
0 to 0 a The preparation of the membrane-anchoring compounds is O likewise described in detail in the last-mentioned German 0 0 0 oo Offenlegungsschrift.
0 0 0 0 0 The separation of the diastereomers, which is necessary °00,'20 where appropriate, can also be carried out by a variety o .o of methods as described, for example, in Hoppe-Seyler's Z. Physiolog. Chem. 364 (1983) 593. A preferred separation process is described in Example 2.
0002 The partial sequences of the particular FMD proteins can be constructed in a variety of ways known from the literature, cf., for example, Winsch et al. in Houben- Weyl, vol. 15/1,2, Stuttgart, Thieme-Verlag or Wunsch in Angew. Chem. 83 (1971), 773, E. Gross and J. Meienhofer (editors), The Peptides, vol. 1 (1979), 2 (1979), 3 (1981) and 5 (1983), Academic Press, New York, or German Offenlegungsschrift 3,546,150. A preferred process for the preparation of a partial sequence and of a conjugate is explained in more detail in Example 3.
The invention additionally relates to pharmaceutical or 8 veterinary medical formulations which contain a conjugate of membrane-anchoring compound and partial sequence of a FMD virus. Besides a solvent, there is normally no additional need for additional auxiliaries and carriers or adjuvants for the formulations according to the invention. However, in some cases, it may be worthwhile to add such auxiliaries and/or carriers as well as, where appropriate, adjuvants to the formulations according to the invention. The relevant substances are mixed and dispensed by processes known to those skilled in the art.
The amount of vaccine necessary for reliable immunization of an animal depends on the species, on the membraneanchoring compound(s) and on the partial sequence(s) of the FMD virus and should be determined empirically in the individual case. For example, sufficient for reliable immunization of a guinea pig against FMD virus serotype OK is a single administration of about 100 500 pg of vaccine according to the invention, without further Si, auxiliaries or carriers.
4 9 The invention additionally relates to the use of the described vaccine for raising antibodies in mammals.
a a a Example 1 Conjugation of peptides/proteins with Pam 3 Cys-Ser-Ser-OSu or Pam 3 Cys-Ser-Ser-OH 025 1. Peptides and proteins soluble in DMF 2 pmol of peptide/protein are dissolved in 0.5-1 ml of DMF, and 8 pmol (9.2 mg) of solid Pam 3 Cys-Ser-Ser- OSu are added. A homogeneous solution is obtained by gentle heating and sonication, and 4 pmol of organic base (N-ethylmorpholine) are added. After stirring for 12 h, 1 2 ml of chloroform: methanol are added, and the mixture is cooleu in an ice bath for 2 h.
The sediment is taken up with 1 ml of cold chloro- 9 form:methanol washed in tert.butanol/water (sonicate if necessary) and freeze-dried.
2. Peptides and proteins soluble in water 2 pmol of peptide/protein are dissolved in 0.8 ml of water, and 4 pmol (4.5 mg) Pam 3 Cys-Ser-Ser-OH are added. The mixture is thoroughly sonicated until an emulsion is produced and a pH of 5.0 to 5.5 is set up. After 5 mg of EDC (l-3-dimethylaminopropyl)-3ethylcarbodiimide hydrochloride) dissolved in 100 pl of H 2 0 has been added the mixture is stirred at room temperature for 18 h and then dialyzed twice against 1 1 of distilled H20 each time. The contents of the dialysis tube are freeze-dried.
SExample 2 Separation of the diastereomers of N-palmitoyl-S-[2,3- (bispalmitoyloxy)propyl]-cysteine tert.-butyl ester S(PamaCys-OBu t 2 g of Pam 3 Cys-OBu t are dissolved in 10 ml of mobile phase, dichloromethane/ethyl acetate and loaded onto a column (length 120 cm, diameter 4 cm) packed with MN silica gel 60, 0.063-0.2 mm/70 230 mesh ASTM. At a drop rate of 2 drops/sec, 350 fractions each of 10 ml are Scollected, and an aliquot of each fraction is checked for Pam 3 Cys-OBu t after chromatography on silica gel 60 plates in dichloromethane/ethyl acetate (20:1) and staining with ch:Lorine/TDM reagent.
Fractions 280 315 contain the R,R diastereomer, fractions 316 335 contain a mixture of R,R and R,S, and fractions 336 354 contain the R,S diastereomer of Pam 3 Cys-OBu t After the solvent has been evaporated off in a rotary evaporator and the residue has been taken up in warm tert.-butanol and freeze-dried, 600 mg of R,R-, 370 mg of a mixture of R,R- and and 540 mg of R,S- Pam 3 Cys-OBu t are obtained.
L 1 10 Example 3 Synthesis of N-palmitoyl-S- (bispalmitoyloxy)propyl]cysteinyl-seryl-seryl-VP 1 (135-154) The VP 1 peptide sequence of FMD virus serotype 0 1 K was synthesised by solid-phase peptide synthesis. F-ioc-amino acids were used. The following side-chain protective groups were used: Lys(Boc), His(Fmoc), Arg(Mtr), Ser(tBu), Asp(OtBu), Tyr(tBu). Starting from 1. g of (pbenzoyloxybenzyl alcohol)- resin loaded with Fmoc- Lys(Boc)-OH, (0.47 mmol/g), the following synthesis cycles were performed: N-Activation with 55 piperidine in N-methylpyrrolidone S' (1 x 2 min, 1 x 5 min), preactivation of Fmoc-A-A-OH mmol) in N-methylpyrrolidone (6 ml) with diisopropylcarbodiimide (1.5 mmol) and l-hydroxybenzotriazole mmol) with subsequent coupling for 1.5 h. Washing with N-ethylmorpholine (5 in N-methylpyrrolidone) was followed by repetition of the preactivation and coupling.
The blocking of unreacted amino groups was carried out r' 20 with acetic anhydride (2.5 mmol) and diisopropylamine (1.2 mmol) in N-methylpyrrolidone. After each step the peptide-resin was washed several times with N-methylpyrcE< rolidone, dichloromethane and again with N-methylpyrrolidone.
25 After the resin-bound FMD virus sequence had been synthesized, a part of the peptide was obtained by cleavage or r with trifluoroacetic acid and checked by HPLC, MS, amino acid analysis, chiral phase analysis and sequence analysis. The bonding of 2 serine residues to the resin-bound peptide was followed by coupling of the tripalmitoyl-Sglycerylcysteine. After 4 hours 1 equivalent of N-methylmorpholine was added, and after another hour the lipopeptide-resin was washed. The lipopeptide was separated from the resin using 2 ml of trifluoroacetic acid (containing 100 pl of thioanisole) within 4 1/2 hours. The filtrate
SJ
11 was evaporated, the residue was taken up with acetie acid, and the solution was added to cold ether. The precipitated lipopeptide was washed 3 x with ether.
Further purification was achieved by recrystallization from trifluoroethanol/chloroform in the ratio 1:3 with cold acetone and a few drops of water. The lipopeptide was freeze-dried from tert.-butanol/water in the ratio 3:1.
Example 4 Activity test: Guinea pigs with a weight of 450 to 500 g chosen at random were inoculated intramuscularly or subcutaneously.
mg of the freeze-dried vaccine (N-palmitoyl-S- [(2R,R)-2,3-(bispalmitoyloxy)propyl]-cysteinyl-serylseryl-VP1(135-154)) was emulsified in 500 pl of a 1:1 mixture of 0.05 M phosphate buffer and IntralipidR) (Kabi t Vitrum, Sweden). The mixture was sonicated for 10 s. Four t animals were infected with FMD virus by subcutaneous injection into the left rear paw of at least 500 guinea *.20 pigs units of a virulent 0 1 K FMD virus 21 days after the o inoculation. Control animals were injected with the membrane-anchoring compound or phosphate buffer in place of the vaccine. A high titer of neutralizing antibodies log 0
SN
0 o of 0.36 was found in all the inoculated animals.
The control animals had no antibody titer (blank 0.17).
The titer of neutralizing antibodies was determined as the logarithm of the serum dilution necessary to neutralize 50 of the virus cells in a monolayer of BHK (baby hamster kidney) cells. It was possible to detect antibodies in the inoculated animals by means of an antipeptide ELISA (A42G), which was not possible for the noninoculated animals. Inoculated animals showed no secondary lesions, whereas all the non-inoculated animals showed the complete picture of foot and mouth disease infection.
Claims (13)
1. A synthetic vaccine against foot and mouth disease, which vaccine comprises a conjugate of at least one membrane-anchoring compound and at least one partial sequence of a protein of the foot and mouth disease virus.
2. A synthetic vaccine as claimed in claim 1, which comprises a membrane-anchoring compound and a partial sequence of foot and mouth disease virus, which are linked together covalently.
3. A synthetic vaccine as claimed in either of claims o 1 or 2, wherein the membrane-anchoring compound is o a o a bacterial membrane lipoprotein. 0 0 C
4. A synthetic vaccine as claimed in one or more of a0 o claims 1 3, wherein the membrane-anchoring com- 0 a pound has one of the formulae below R -CO-0-CH 2 R -O-CH 2 R -O-CO-CH2 e R'-CO-O-CH* R'-O-CH R-0-CO-COH* (CH2)- 'H2 )n (CH2)n A A A 2)m (H2)m (H2) m R"-CO-NH--CR H-CH*-CO-*.X R"-CO-NH-CH*-CO-X I. ii. III. SR -NH-CO-CH2 R -CO-CH 2 R'-NH-CO-CH* R'-CO-CH* n CH 2)n B A A A (H 2 )m (H 2 )m (H 2 m R"-CO-NH-CH*-CO-X R"-CO-NH-CH*-CO-X R"-NH-CO-CH*-CO-X IV. V. 13 j j 13 R i -CH 2 R 2 -CH* (CH 2 )n (6H 2 )m R-CO-NH-CH*-CO-X VII. in which A can be sulfur, oxygen, disulfide methylene (-CH 2 or -NH-; n 0 to 5, m 1 or 2; C* is an asymmetric carbon atom with the R or S con- figuration, R, R' and R" are identical or different and each is hydrogen or an alkyl, alkenyl or alkynyl group which has 7 to 25 carbon atoms and which can be substitu- ted by hydroxyl, amino, oxo, acyl, alkyl or cyclo- alkyl groups, B in formula VI can have the meaning of each of the -(CH 2 )n-(substituted alkyl) radicals listed in formulae I-V, and R, and R 2 are identical or different and have the same meanings as R, R' and R" but can also be -OR, -0-COR, -COOR, NHCOR or -CONHR, where X is a chain of 1 to 10 amino acids to which the partial sequence of the virus is bonded.
A synthetic vaccine as claimed in one or more of claims 1 4, wherein the partial sequence of the foot and mouth disease virus which is bonded to the membrane-anchoring compound is selected from the group comprising sequence-(134-154) S-(135-154) -(134-158) -(134-160) -(141-160) S-(141-158) 14 14 sequence-(200-213) "-(200-210) -(161-180), or the C-terminal amidated or alkylamidated forms thereof, it being possible to use the sequences of all known serotypes and subtypes.
6. A synthetic vaccine as claimed in one or more of claims 1 5, wherein the partial sequence of the foot and mouth disease virus VP 1 (135-154) is bonded to the membrane-anchoring compound.
7. A synthetic vaccine as claimed in one or more of claims 1 6, which comprises a mixture of peptides from various sero- and/or subtypes of the foot and j .a c mouth disease virus, each of which is covalently bonded to the membrane-anchoring compound or membrane-anchoring compounds. e1 C
8. A synthetic vaccine as claimed in one or more of claims 1 7, which comprises a mixture of sequences VP1 134-160 of serotypes 0, A or C bonded to the oo °membrane-anchoring compound N-palmitoyl-S-[2,3- 0 (bispalmitoyloxy)propyl]-cysteinyl-seryl-serine. 0 *pt
9. A synthetic vaccine as claimed in one or more of claims 1 8, which vaccine comprises N-palmitoyl- S-[2,3-(bispalmitoyloxy)propyl]-cysteinyl-seryl- seryl-VP 1 (135-154), it being possible for the a membrane-anchoring compound to be in the form of the 0 R,S or R,R diastereomer or of a mixture of diastere- omers.
A synthetic vaccine as claimed in one or more of claims 1 to 9, wherein the membrane-anchoring compound is in the form of the R,R diastereomer.
11. A process for the preparation of a synthetic vaccine as claimed in one or more of claims 1 10, which 15 comprises the partial sequences of the foot and mouth disease virus which have been prepared in a manner known per se being bonded to the membrane- anchoring compound by a conjugation reaction.
12. A pharmaceutical or veterinary medical formulation, which contains a synthetic vaccine as claimed in one or more of claims 1 11, where appropriate in addition to customary auxiliaries and/or carriers, adjuvants and/or other vaccines.
13. The use of a synthetic vaccine as claimed in one or more of claims 1 12 for raising antibodies against foot and mouth disease viruses in mammals. iI S fr S' DATED this 20th day of April 1989. Sc HOECHST-AKTIENGESELLSCHAFT Ce EDWD. WATERS SONS PATENT ATTORNEYS C; 50 QUEEN STREET C' MELBOURNE.- VIC.- 3000. o r
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| DE3813821 | 1988-04-22 | ||
| DE3813821A DE3813821A1 (en) | 1988-04-22 | 1988-04-22 | SYNTHETIC VACCINE AGAINST MOUTH AND CLAUS DISEASE AND METHOD FOR THEIR PRODUCTION |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| AU3326589A AU3326589A (en) | 1989-10-26 |
| AU619826B2 true AU619826B2 (en) | 1992-02-06 |
Family
ID=6352780
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| AU33265/89A Ceased AU619826B2 (en) | 1988-04-22 | 1989-04-21 | A synthetic vaccine against foot and mouth disease and a process for the preparation thereof |
Country Status (15)
| Country | Link |
|---|---|
| EP (1) | EP0338437B1 (en) |
| JP (1) | JP2837866B2 (en) |
| AR (1) | AR243081A1 (en) |
| AT (1) | ATE118507T1 (en) |
| AU (1) | AU619826B2 (en) |
| CA (1) | CA1333563C (en) |
| DE (2) | DE3813821A1 (en) |
| DK (1) | DK175629B1 (en) |
| ES (1) | ES2068215T3 (en) |
| GR (1) | GR3015358T3 (en) |
| IE (1) | IE67124B1 (en) |
| NZ (1) | NZ228824A (en) |
| PT (1) | PT90333B (en) |
| RU (1) | RU1836102C (en) |
| ZA (1) | ZA892954B (en) |
Families Citing this family (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE3937412A1 (en) * | 1989-11-10 | 1991-05-16 | Hoechst Ag | SYNTHETIC VACCINE FOR THE SPECIFIC INDUCTION OF CYTOTOXIC T-LYMPHOZYTES |
| US6074650A (en) * | 1985-06-24 | 2000-06-13 | Hoechst Aktiengesellschaft | Membrane anchor/active compound conjugate, its preparation and its uses |
| US6024964A (en) * | 1985-06-24 | 2000-02-15 | Hoechst Aktiengesellschaft | Membrane anchor/active compound conjugate, its preparation and its uses |
| GB9915074D0 (en) * | 1999-06-28 | 1999-08-25 | Cortecs Plc | Ligand-binding composition |
| EA031379B1 (en) | 2010-03-23 | 2018-12-28 | Новартис Аг | Compounds (cystein based lipopeptides) and compositions as tlr2 agonists used for treating infections, inflammations, respiratory diseases etc. |
| CN109893648A (en) | 2013-06-28 | 2019-06-18 | 奥克兰联合服务有限公司 | Amino acid conjugate and peptide conjugate and conjugation methods |
| RU2017126206A (en) | 2014-12-23 | 2019-01-25 | Маргарет Анне БРИМБЛЕ | Amino acid and peptide conjugates and directions for their use |
| TW201735952A (en) | 2016-02-26 | 2017-10-16 | 瑪格蕾特 安 布萊博 | Amino acid and peptide conjugates and conjugation process |
Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| AU3449784A (en) * | 1983-10-22 | 1985-04-26 | Akzo N.V. | Preparation of immunogens consisting of antigenic determinants bound to glycoside-containing carriers |
| AU5894386A (en) * | 1985-06-24 | 1987-01-08 | Sanofi-Aventis Deutschland Gmbh | Membrane anchor/active compound conjugate, its preparation and its use |
| AU573574B2 (en) * | 1983-03-08 | 1988-06-16 | Chiron Mimotopes Pty Ltd | Immunogenic deteminants of foot and mouth disease virus |
Family Cites Families (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| ZA824174B (en) * | 1981-06-16 | 1983-04-27 | Genentech Inc | Production of foot and mouth disease vaccine from microbially expressed antigens thereof |
| ZA831854B (en) * | 1982-03-26 | 1984-01-25 | Biogen Nv | Small peptides with the specificity of foot and mouth disease viral antigens |
| CA1247080A (en) * | 1983-03-08 | 1988-12-20 | Commonwealth Serum Laboratories Commission | Antigenically active amino acid sequences |
| JPS59500719A (en) * | 1983-04-06 | 1984-04-26 | ビトル ジエイムズ エル | Synthetic picornavirus antigen |
| JPS61292398A (en) * | 1985-06-19 | 1986-12-23 | 富士通株式会社 | Manufacture of multilayer circuit board |
-
1988
- 1988-04-22 DE DE3813821A patent/DE3813821A1/en not_active Withdrawn
-
1989
- 1989-04-12 AR AR89313718A patent/AR243081A1/en active
- 1989-04-13 ES ES89106628T patent/ES2068215T3/en not_active Expired - Lifetime
- 1989-04-13 AT AT89106628T patent/ATE118507T1/en not_active IP Right Cessation
- 1989-04-13 DE DE58908990T patent/DE58908990D1/en not_active Expired - Fee Related
- 1989-04-13 EP EP89106628A patent/EP0338437B1/en not_active Expired - Lifetime
- 1989-04-20 DK DK198901928A patent/DK175629B1/en not_active IP Right Cessation
- 1989-04-20 NZ NZ228824A patent/NZ228824A/en unknown
- 1989-04-20 PT PT90333A patent/PT90333B/en not_active IP Right Cessation
- 1989-04-21 RU SU894613910A patent/RU1836102C/en active
- 1989-04-21 CA CA000597445A patent/CA1333563C/en not_active Expired - Fee Related
- 1989-04-21 ZA ZA892954A patent/ZA892954B/en unknown
- 1989-04-21 IE IE129689A patent/IE67124B1/en not_active IP Right Cessation
- 1989-04-21 AU AU33265/89A patent/AU619826B2/en not_active Ceased
- 1989-04-21 JP JP1100345A patent/JP2837866B2/en not_active Expired - Fee Related
-
1995
- 1995-03-10 GR GR950400516T patent/GR3015358T3/en unknown
Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| AU573574B2 (en) * | 1983-03-08 | 1988-06-16 | Chiron Mimotopes Pty Ltd | Immunogenic deteminants of foot and mouth disease virus |
| AU3449784A (en) * | 1983-10-22 | 1985-04-26 | Akzo N.V. | Preparation of immunogens consisting of antigenic determinants bound to glycoside-containing carriers |
| AU5894386A (en) * | 1985-06-24 | 1987-01-08 | Sanofi-Aventis Deutschland Gmbh | Membrane anchor/active compound conjugate, its preparation and its use |
Also Published As
| Publication number | Publication date |
|---|---|
| RU1836102C (en) | 1993-08-23 |
| DE58908990D1 (en) | 1995-03-23 |
| EP0338437B1 (en) | 1995-02-15 |
| DK192889D0 (en) | 1989-04-20 |
| ES2068215T3 (en) | 1995-04-16 |
| DK192889A (en) | 1989-10-23 |
| IE891296L (en) | 1989-10-22 |
| PT90333B (en) | 1994-08-31 |
| PT90333A (en) | 1989-11-10 |
| JP2837866B2 (en) | 1998-12-16 |
| EP0338437A3 (en) | 1991-05-08 |
| ATE118507T1 (en) | 1995-03-15 |
| DK175629B1 (en) | 2004-12-27 |
| EP0338437A2 (en) | 1989-10-25 |
| AU3326589A (en) | 1989-10-26 |
| GR3015358T3 (en) | 1995-06-30 |
| IE67124B1 (en) | 1996-03-06 |
| DE3813821A1 (en) | 1989-11-02 |
| CA1333563C (en) | 1994-12-20 |
| AR243081A1 (en) | 1993-07-30 |
| NZ228824A (en) | 1992-05-26 |
| JPH026410A (en) | 1990-01-10 |
| ZA892954B (en) | 1989-12-27 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| EP0652896B1 (en) | Peptide compounds | |
| Wiesmüller et al. | Novel low-molecular-weight synthetic vaccine against foot-and-mouth disease containing a potent B-cell and macrophage activator | |
| DE69432475T2 (en) | OF HUMAN T CELLS IMMUNODOMINANT EPIROPEN OF THE VIRUS DER C-HEPATITIS | |
| US4499080A (en) | Synthetic ST toxin, process for its preparation and its use as a vaccinating agent | |
| JP2002518461A (en) | Synthetic peptide vaccine for foot-and-mouth disease | |
| EA006308B1 (en) | Hiv peptides, antigens, vaccine compositions, immunoassay kit and method of detecting antibodies induced by hiv | |
| US6074650A (en) | Membrane anchor/active compound conjugate, its preparation and its uses | |
| WO1995031480A1 (en) | Heterodimer polypeptide immunogen carrier composition and method | |
| US6024964A (en) | Membrane anchor/active compound conjugate, its preparation and its uses | |
| AU619826B2 (en) | A synthetic vaccine against foot and mouth disease and a process for the preparation thereof | |
| CA1271717A (en) | Polypeptides useful in vaccination against enteroviruses | |
| FI120149B (en) | Purified P5 protein of non-typable Haemophilus influenzae as vaccine against a non-typable Haemophilus influenzae strain | |
| US7341994B2 (en) | GD3-mimetic peptides | |
| EP0227604A2 (en) | Use of oligopeptides in the treatment of viral infections | |
| EP0079934B1 (en) | Antigenic linear peptide compounds | |
| KR20030034194A (en) | Ligand/receptor specificity exachangers that redirect antibodies to receptors on a pathogen | |
| Muller et al. | Specific antibody response towards predicted epitopes of the epidermal growth factor receptor induced by a thermostable synthetic peptide adjuvant conjugate. | |
| Haro et al. | Different approaches to potentiate the immune response induced by a 12-mer synthetic peptide | |
| EP2647390A1 (en) | Peptide vaccines for the prevention of foot-and-mouth disease | |
| NZ218760A (en) | Oligopeptides useful for immunisation against viruses especially rhino viruses | |
| Maugeri | Synthesis of new adjuvants and carriers for foot and mouth disease virus (fmdv) | |
| Chen et al. | Artificial proteins as candidate AIDS vaccines | |
| EP0547681A2 (en) | Synthetic peptides comprising a cyclic HIV principal neutralizing determinant and a lipopeptide | |
| MXPA00011752A (en) | Synthetic somatostatin immunogen for growth promotion in farm animals | |
| MXPA99005693A (en) | Vaccine for the reversible immunocastration of mammals |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PC | Assignment registered |
Owner name: AVENTIS PHARMA DEUTSCHLAND GMBH Free format text: FORMER OWNER WAS: HOECHST AKTIENGESELLSCHAFT |