WO1986001826A1 - Hepatitis a virus purified and triply cloned - Google Patents
Hepatitis a virus purified and triply cloned Download PDFInfo
- Publication number
- WO1986001826A1 WO1986001826A1 PCT/US1985/001769 US8501769W WO8601826A1 WO 1986001826 A1 WO1986001826 A1 WO 1986001826A1 US 8501769 W US8501769 W US 8501769W WO 8601826 A1 WO8601826 A1 WO 8601826A1
- Authority
- WO
- WIPO (PCT)
- Prior art keywords
- virus
- hepatitis
- cloned
- hav
- strain
- Prior art date
Links
- 241000709721 Hepatovirus A Species 0.000 title claims abstract description 29
- 241000700605 Viruses Species 0.000 claims abstract description 26
- 238000000034 method Methods 0.000 claims abstract description 11
- 208000006454 hepatitis Diseases 0.000 claims abstract description 10
- 231100000283 hepatitis Toxicity 0.000 claims abstract description 10
- 241000288906 Primates Species 0.000 claims abstract description 7
- 230000005875 antibody response Effects 0.000 claims abstract 2
- 239000000463 material Substances 0.000 claims description 11
- 229960005486 vaccine Drugs 0.000 claims description 9
- 230000002238 attenuated effect Effects 0.000 claims description 7
- 208000005252 hepatitis A Diseases 0.000 claims description 6
- 230000001681 protective effect Effects 0.000 claims description 4
- 241000124008 Mammalia Species 0.000 claims description 2
- 238000002255 vaccination Methods 0.000 claims description 2
- 238000002347 injection Methods 0.000 claims 2
- 239000007924 injection Substances 0.000 claims 2
- 239000000203 mixture Substances 0.000 claims 2
- 238000010790 dilution Methods 0.000 abstract description 13
- 239000012895 dilution Substances 0.000 abstract description 13
- 241001243761 Human hepatitis A virus Species 0.000 abstract description 3
- 239000002054 inoculum Substances 0.000 abstract description 3
- 241000282579 Pan Species 0.000 description 16
- 241001465754 Metazoa Species 0.000 description 8
- 238000004113 cell culture Methods 0.000 description 5
- 238000010367 cloning Methods 0.000 description 5
- 208000015181 infectious disease Diseases 0.000 description 4
- 230000001154 acute effect Effects 0.000 description 3
- 210000004027 cell Anatomy 0.000 description 3
- 241001515942 marmosets Species 0.000 description 3
- 239000002245 particle Substances 0.000 description 3
- 241000282552 Chlorocebus aethiops Species 0.000 description 2
- 108090000790 Enzymes Proteins 0.000 description 2
- 102000004190 Enzymes Human genes 0.000 description 2
- 241000282414 Homo sapiens Species 0.000 description 2
- 241000282577 Pan troglodytes Species 0.000 description 2
- 239000012297 crystallization seed Substances 0.000 description 2
- 238000011081 inoculation Methods 0.000 description 2
- 208000019423 liver disease Diseases 0.000 description 2
- 230000004044 response Effects 0.000 description 2
- 230000003612 virological effect Effects 0.000 description 2
- 102100036475 Alanine aminotransferase 1 Human genes 0.000 description 1
- 108010082126 Alanine transaminase Proteins 0.000 description 1
- 208000034657 Convalescence Diseases 0.000 description 1
- 241000709661 Enterovirus Species 0.000 description 1
- 208000019331 Foodborne disease Diseases 0.000 description 1
- 208000037319 Hepatitis infectious Diseases 0.000 description 1
- 241000709664 Picornaviridae Species 0.000 description 1
- 208000000474 Poliomyelitis Diseases 0.000 description 1
- 208000034817 Waterborne disease Diseases 0.000 description 1
- 239000000427 antigen Substances 0.000 description 1
- 102000036639 antigens Human genes 0.000 description 1
- 108091007433 antigens Proteins 0.000 description 1
- 230000005540 biological transmission Effects 0.000 description 1
- 150000001768 cations Chemical class 0.000 description 1
- 238000006243 chemical reaction Methods 0.000 description 1
- 238000002405 diagnostic procedure Methods 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
- 230000028993 immune response Effects 0.000 description 1
- 230000036039 immunity Effects 0.000 description 1
- 230000006698 induction Effects 0.000 description 1
- 230000002458 infectious effect Effects 0.000 description 1
- 238000002955 isolation Methods 0.000 description 1
- 210000003734 kidney Anatomy 0.000 description 1
- 210000003292 kidney cell Anatomy 0.000 description 1
- 210000004185 liver Anatomy 0.000 description 1
- 230000007505 plaque formation Effects 0.000 description 1
- 238000002360 preparation method Methods 0.000 description 1
- 230000005180 public health Effects 0.000 description 1
- 238000007619 statistical method Methods 0.000 description 1
- 230000002311 subsequent effect Effects 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N7/00—Viruses; Bacteriophages; Compositions thereof; Preparation or purification thereof
- C12N7/04—Inactivation or attenuation; Producing viral sub-units
- C12N7/08—Inactivation or attenuation by serial passage of virus
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N7/00—Viruses; Bacteriophages; Compositions thereof; Preparation or purification thereof
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K39/00—Medicinal preparations containing antigens or antibodies
- A61K39/12—Viral antigens
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K39/00—Medicinal preparations containing antigens or antibodies
- A61K39/12—Viral antigens
- A61K39/29—Hepatitis virus
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K39/00—Medicinal preparations containing antigens or antibodies
- A61K2039/51—Medicinal preparations containing antigens or antibodies comprising whole cells, viruses or DNA/RNA
- A61K2039/525—Virus
- A61K2039/5254—Virus avirulent or attenuated
-
- 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
- A61K2039/54—Medicinal preparations containing antigens or antibodies characterised by the route of administration
-
- 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
-
- 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
- C12N2770/32411—Hepatovirus, i.e. hepatitis A virus
- C12N2770/32434—Use of virus or viral component as vaccine, e.g. live-attenuated or inactivated virus, VLP, viral protein
-
- 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
- C12N2770/32411—Hepatovirus, i.e. hepatitis A virus
- C12N2770/32451—Methods of production or purification of viral material
-
- 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
- C12N2770/32411—Hepatovirus, i.e. hepatitis A virus
- C12N2770/32461—Methods of inactivation or attenuation
- C12N2770/32464—Methods of inactivation or attenuation by serial passage
-
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02A—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE
- Y02A50/00—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE in human health protection, e.g. against extreme weather
- Y02A50/30—Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change
Definitions
- Hepatitis A virus has a world-wide dis ⁇ tribution. It is responsible for as many as 100,000 cases of hepatitis per year in the United States where, as in most of the developed world, it accounts for perhaps 20-25 percent of clinical hepatitis. It is highly endemic throughout the developing world and infects virtually 100 percent of the population by age ten in such regions. It is a picornavirus with many of the characteristics of an enterovirus and has been class ⁇ ified as such. It is spread principally by fecal-oral contaminat iorr and has been responsible for many epidemics of water-borne or food-borne disease. However, it is most commonly spread by person-to-person contact. Parenteral transmission of HAV is very rare.
- U.S. Patent 4,164,566 (Provost et al) teaches the development of _ij ⁇ vitro hepatitis A virus cell cul- tures. Provost et al, however, use a different strain of HAV which requires at least 5 passages in a sub-human primate in order to produce HAV.
- the purpose of the inventors' U.S. Patent Application Serial No. 366,165 invention is to show that HAV can be isolated and serially passaged in primary African green monkey kidney (AQVtK) cell cultures taken directly from human clinical specimens.
- AQVtK primary African green monkey kidney
- HM-175 strain of hepatitis A virus has been deposited in the American Type Culture Collection under the patent procedures prior to the filing of this appli ⁇ cation, thus affording permanency of the deposit and ready availability to the public upon issuance of a patent .
- the triple cloning of master seed lots of the HM-175 strain of hepatitis A virus has resulted in a superior vaccine which produces antibodies but not disease in chimpanzees and other primates such as marmosets.
- the protection of the chimpanzees challenged by wild-type virus is a significant indicia of vaccine.
- tissue culture passaged virus The stability of attentuation of the tissue culture passaged virus was shown by inoculation (percutaneously, preferably intravenously) of additional chimpanzees with the acute phase stools from previously inoculated animals, Table 3. Recipient animals developed no bio ⁇ chemical evidence of liver disease but hepatitis A anti ⁇ body was produced.
- This vaccine is utilizable for mammals or higher primates which include man, chimpanzees and marmosets.
- the triple cloned viral material (3X) is homogeneously superior to the twice cloned (2X) virus for a uniform virus preparation suitable for a vaccine.
- a master seed lot of virus as explained herein is produced from triply cloned virus by terminal dilutions at passage levels 10 and 20 (Cunningham, A Laboratory Guide in Virology, 5th ed., Burgess Pub. Co., 1963, pp. 144- 145).
- the purpose of the dilution is that the highest dilution positive tubes of the procedure originated from a single virus particle, thus providing biological uni- formity of the product.
- Cloning of the virus was done as follows: a pool of uncloned virus was diluted serially 10 -1 to 10-8. Each dilution was used to inoculate 9 tubes of primary African green monkey cell cultures. The cells were allowed to grow and the virus grew in the cells, harvested after 8 weeks. Each tube was checked for the presence of hepatitis A virus antigen at that time and of the tubes at the highest dilutions, i.e., the 10 dilu ⁇ tion, there were some negative and some positive tubes. At this dilution, based upon statistical analysis, the positive tubes originated from a single virus particle. The negative tubes contained no virus. Of the tubes that were positive, two tubes were harvested from each term ⁇ inal dilution series.
- Clone #2 (TC passage 20) was inoculated intravenously into 4 susceptible chimpanzees. Only 1 of the 4 animals had a very mild borderline hepatitis. All four developed protective antibody. Similarly, 1 of 2 susceptible chimpanzees inoculated intravenously with Clone #4 (TC passage 9) was infected without hepatitis but with the development of protective antibody.
Landscapes
- Life Sciences & Earth Sciences (AREA)
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Virology (AREA)
- Microbiology (AREA)
- Medicinal Chemistry (AREA)
- Immunology (AREA)
- General Health & Medical Sciences (AREA)
- Engineering & Computer Science (AREA)
- Organic Chemistry (AREA)
- Zoology (AREA)
- Wood Science & Technology (AREA)
- Genetics & Genomics (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Mycology (AREA)
- Epidemiology (AREA)
- Pharmacology & Pharmacy (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- Animal Behavior & Ethology (AREA)
- Biochemistry (AREA)
- Biotechnology (AREA)
- General Engineering & Computer Science (AREA)
- Biomedical Technology (AREA)
- Communicable Diseases (AREA)
- Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
- Micro-Organisms Or Cultivation Processes Thereof (AREA)
- Medicinal Preparation (AREA)
- Peptides Or Proteins (AREA)
Priority Applications (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| KR860700275A KR860700263A (ko) | 1984-09-19 | 1985-09-18 | 정제 및 삼중 클론된 간염 a비루스 |
| FI861966A FI86376C (fi) | 1984-09-19 | 1986-05-12 | Foerfarande foer framstaellning av renad och tre gaonger klonad hepatitis-a-virus. |
| DK227786A DK227786A (da) | 1984-09-19 | 1986-05-16 | Hepatitis a virus renset og klonet tre gange |
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US06/652,067 US4620978A (en) | 1982-04-07 | 1984-09-19 | Hepatitis A virus purified and triply cloned |
| US652,067 | 1984-09-19 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| WO1986001826A1 true WO1986001826A1 (en) | 1986-03-27 |
Family
ID=24615385
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| PCT/US1985/001769 WO1986001826A1 (en) | 1984-09-19 | 1985-09-18 | Hepatitis a virus purified and triply cloned |
Country Status (16)
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP0339667A2 (en) * | 1988-04-28 | 1989-11-02 | Juridical Foundation The Chemo-Sero-Therapeutic Research Institute | Hepatitis A,B,-combined adjuvanted vaccine |
| WO1994021292A1 (en) * | 1993-03-23 | 1994-09-29 | Smithkline Beecham Biologicals (S.A.) | Vaccine compositions containing 3-o deacylated monophosphoryl lipid a |
Families Citing this family (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4894228A (en) * | 1982-04-07 | 1990-01-16 | The United States Of America As Represented By The Department Of Health And Human Services | Vaccine against hepatitis A virus |
| USRE37381E1 (en) * | 1982-04-07 | 2001-09-18 | The United States Of America As Represented By The Department Of Health And Human Services | Vaccine against hepatitis A virus |
| US5268292A (en) * | 1988-06-27 | 1993-12-07 | Robertson Betty H | Reproducible generation of high yields of hepatitis A virus by cell culture |
| WO1994006446A1 (en) | 1992-09-18 | 1994-03-31 | Smithkline Beecham Biologicals, S.A. | Hepatitis a virus vaccines |
| HRP950097A2 (en) | 1994-03-08 | 1997-06-30 | Merck & Co Inc | Hepatitis a virus culture process |
| US5766906A (en) * | 1994-07-11 | 1998-06-16 | The University Of North Carolina At Chapel Hill | Hepatitis A virus deletion mutants and vaccine formulations containing the same |
| US10265265B2 (en) * | 2007-03-15 | 2019-04-23 | Drug Delivery Solutions Limited | Topical composition |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4164566A (en) * | 1978-08-17 | 1979-08-14 | Merck & Co., Inc. | Hepatitis a virus cell culture in vitro |
| US4532215A (en) * | 1982-04-07 | 1985-07-30 | The United States Of America As Represented By The Department Of Health And Human Services | Isolation of hepatitis A virus strain HM-175 |
-
1984
- 1984-09-19 US US06/652,067 patent/US4620978A/en not_active Expired - Lifetime
-
1985
- 1985-09-17 ZA ZA857134A patent/ZA857134B/xx unknown
- 1985-09-17 NZ NZ213513A patent/NZ213513A/xx unknown
- 1985-09-18 KR KR860700275A patent/KR860700263A/ko not_active Application Discontinuation
- 1985-09-18 WO PCT/US1985/001769 patent/WO1986001826A1/en not_active Application Discontinuation
- 1985-09-18 PT PT81150A patent/PT81150B/pt unknown
- 1985-09-18 AU AU48620/85A patent/AU583306B2/en not_active Expired
- 1985-09-18 EP EP19850904746 patent/EP0196316A4/en not_active Ceased
- 1985-09-18 CA CA000491066A patent/CA1260392A/en not_active Expired
- 1985-09-18 JP JP60504247A patent/JPS62500659A/ja active Pending
- 1985-09-19 ES ES547115A patent/ES8701837A1/es not_active Expired
- 1985-09-19 IL IL76417A patent/IL76417A/xx not_active IP Right Cessation
- 1985-09-20 GR GR852293A patent/GR852293B/el unknown
-
1986
- 1986-04-24 NO NO86861619A patent/NO169601C/no not_active IP Right Cessation
- 1986-05-12 FI FI861966A patent/FI86376C/fi not_active IP Right Cessation
- 1986-05-16 DK DK227786A patent/DK227786A/da active IP Right Revival
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4164566A (en) * | 1978-08-17 | 1979-08-14 | Merck & Co., Inc. | Hepatitis a virus cell culture in vitro |
| US4532215A (en) * | 1982-04-07 | 1985-07-30 | The United States Of America As Represented By The Department Of Health And Human Services | Isolation of hepatitis A virus strain HM-175 |
Non-Patent Citations (6)
| Title |
|---|
| DEINHARDT and DEINHARDT, Animal Models. 1984. In Hepatitis A. (ED) R.J. GERETY Academic Press, N.Y. * |
| Hepatitis A. 1984. (ED) R.J. GERETY. Academic Press, N.Y. Chap.1, 13 * |
| Infection and Immun. Vol 32, pages 388-393, 1981. R. DAEMER et al. Propagation of Human Hepatitis A Virus in African Green Monkey Kidney Cell Culture * |
| Proc. Soc. Exp. Biol. Med. Vol. 170, pages 8-14. 1982. P. PROVOST et al. Progress toward a Live, Attenuated Human Hepatitis A virus * |
| Proc. Soc. Exp. Biol. Med. Vol. 172, pages 357-363. 1983 P. PROVOST et al. Studies in Chimpanzees of Live, Attenuated Hepatitis A vaccine Candidates * |
| See also references of EP0196316A4 * |
Cited By (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP0339667A2 (en) * | 1988-04-28 | 1989-11-02 | Juridical Foundation The Chemo-Sero-Therapeutic Research Institute | Hepatitis A,B,-combined adjuvanted vaccine |
| EP0339667A3 (en) * | 1988-04-28 | 1990-06-13 | Juridical Foundation The Chemo-Sero-Therapeutic Research Institute | Hepatitis a,b,-combined adjuvanted vaccine |
| US5151023A (en) * | 1988-04-28 | 1992-09-29 | Juridical Foundation The Chemo-Sero-Therapeutic Research Institute | Hepatitis a,b-combined adjuvanted vaccine |
| WO1994021292A1 (en) * | 1993-03-23 | 1994-09-29 | Smithkline Beecham Biologicals (S.A.) | Vaccine compositions containing 3-o deacylated monophosphoryl lipid a |
| EP0812593A1 (en) * | 1993-03-23 | 1997-12-17 | SMITHKLINE BEECHAM BIOLOGICALS s.a. | Vaccine compositions containing 3-0 deacylated monophosphoryl lipid a |
| US5776468A (en) * | 1993-03-23 | 1998-07-07 | Smithkline Beecham Biologicals (S.A.) | Vaccine compositions containing 3-0 deacylated monophosphoryl lipid A |
| EP1175912A1 (en) * | 1993-03-23 | 2002-01-30 | SmithKline Beecham Biologics SA | Vaccine compositions containing 3-O deacylated monophosphoryl lipid A |
Also Published As
| Publication number | Publication date |
|---|---|
| NO169601C (no) | 1992-07-15 |
| FI86376B (fi) | 1992-05-15 |
| PT81150B (pt) | 1987-10-20 |
| IL76417A0 (en) | 1986-01-31 |
| FI86376C (fi) | 1992-08-25 |
| FI861966A0 (fi) | 1986-05-12 |
| NZ213513A (en) | 1989-03-29 |
| EP0196316A1 (en) | 1986-10-08 |
| CA1260392A (en) | 1989-09-26 |
| AU583306B2 (en) | 1989-04-27 |
| ES547115A0 (es) | 1986-12-01 |
| EP0196316A4 (en) | 1987-01-28 |
| ZA857134B (en) | 1987-05-27 |
| NO861619A (no) | 1986-04-24 |
| DK227786D0 (da) | 1986-05-16 |
| FI861966A (fi) | 1986-05-12 |
| US4620978A (en) | 1986-11-04 |
| ES8701837A1 (es) | 1986-12-01 |
| GR852293B (US06373033-20020416-M00071.png) | 1986-01-21 |
| KR860700263A (ko) | 1986-08-01 |
| JPS62500659A (ja) | 1987-03-19 |
| AU4862085A (en) | 1986-04-08 |
| PT81150A (en) | 1985-10-01 |
| IL76417A (en) | 1990-12-23 |
| DK227786A (da) | 1986-05-16 |
| NO169601B1 (no) | 1992-04-06 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CA1135621A (en) | Hepatitis a virus cell culture in vitro | |
| Provost et al. | Progress toward a live, attenuated human hepatitis A vaccine | |
| Binn et al. | Preparation of a prototype inactivated hepatitis A virus vaccine from infected cell cultures | |
| US6680060B2 (en) | Hepatitus A virus vaccines | |
| Falk et al. | Herpesvirus ateles: properties of an oncogenic herpesvirus isolated from circulating lymphocytes of spider monkeys (Ateles sp.) | |
| AU583306B2 (en) | Triply cloned hepatitis a live attenuated virus | |
| CA1164799A (en) | Cell culture of hepatitis a virus | |
| US5021348A (en) | Attenuated hepatitis A virus | |
| Provost et al. | Isolation of Hepatitis A Virus in Vitr o in Cell Culture Directly from Human Specimens | |
| EP0339668A2 (en) | Hepatitis A virus antigen | |
| CA1292690C (en) | Vaccine comprising an immunogenic protein and, as an adjuvant, a substantially non-immunogenic sequentially homologous peptide | |
| CN109022456B (zh) | 一种表达卵形疟原虫ama1蛋白的病毒疫苗的制备方法 | |
| US5514376A (en) | Cell culture of hepatitis A virus | |
| Murray | The Leeuwenhoek Lecture, 1985-A molecular biologist’s view of viral hepatitis | |
| Hilleman | Immunologic prevention of human hepatitis | |
| ABE et al. | Effects of arildone on the immunogenicity of formalin-inactivated polioviruses | |
| CN85107525A (zh) | 将肝炎a病毒净化及三重无性繁殖 | |
| JPS6391329A (ja) | Ａ型肝炎ワクチン |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| AK | Designated states |
Kind code of ref document: A1 Designated state(s): AU DK FI JP KR NO |
|
| AL | Designated countries for regional patents |
Kind code of ref document: A1 Designated state(s): AT BE CH DE FR GB IT LU NL SE |
|
| WWE | Wipo information: entry into national phase |
Ref document number: 1985904746 Country of ref document: EP |
|
| WWE | Wipo information: entry into national phase |
Ref document number: 861966 Country of ref document: FI |
|
| WWP | Wipo information: published in national office |
Ref document number: 1985904746 Country of ref document: EP |
|
| WWG | Wipo information: grant in national office |
Ref document number: 861966 Country of ref document: FI |
|
| WWR | Wipo information: refused in national office |
Ref document number: 1985904746 Country of ref document: EP |
|
| WWW | Wipo information: withdrawn in national office |
Ref document number: 1985904746 Country of ref document: EP |