BE832758A - BIVALENT VACCINES AGAINST RUBELLA AND CYTOMEGALIA - Google Patents
BIVALENT VACCINES AGAINST RUBELLA AND CYTOMEGALIAInfo
- Publication number
- BE832758A BE832758A BE159475A BE159475A BE832758A BE 832758 A BE832758 A BE 832758A BE 159475 A BE159475 A BE 159475A BE 159475 A BE159475 A BE 159475A BE 832758 A BE832758 A BE 832758A
- Authority
- BE
- Belgium
- Prior art keywords
- emi
- rubella
- virus
- vaccine
- strain
- Prior art date
Links
- 229940031416 bivalent vaccine Drugs 0.000 title description 9
- 201000005404 rubella Diseases 0.000 title description 8
- 229960005486 vaccine Drugs 0.000 claims description 18
- 241000700605 Viruses Species 0.000 claims description 15
- 241000710799 Rubella virus Species 0.000 claims description 12
- 239000000203 mixture Substances 0.000 claims description 10
- 230000002238 attenuated effect Effects 0.000 claims description 9
- 206010011831 Cytomegalovirus infection Diseases 0.000 claims description 3
- 230000000087 stabilizing effect Effects 0.000 claims description 3
- 229930006000 Sucrose Natural products 0.000 description 4
- CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 description 4
- 239000007864 aqueous solution Substances 0.000 description 4
- 239000005720 sucrose Substances 0.000 description 4
- 102000008100 Human Serum Albumin Human genes 0.000 description 3
- 108091006905 Human Serum Albumin Proteins 0.000 description 3
- WDRWZVWLVBXVOI-QTNFYWBSSA-L dipotassium;(2s)-2-aminopentanedioate Chemical compound [K+].[K+].[O-]C(=O)[C@@H](N)CCC([O-])=O WDRWZVWLVBXVOI-QTNFYWBSSA-L 0.000 description 3
- 238000004108 freeze drying Methods 0.000 description 3
- 235000013919 monopotassium glutamate Nutrition 0.000 description 3
- ZGTMUACCHSMWAC-UHFFFAOYSA-L EDTA disodium salt (anhydrous) Chemical compound [Na+].[Na+].OC(=O)CN(CC([O-])=O)CCN(CC(O)=O)CC([O-])=O ZGTMUACCHSMWAC-UHFFFAOYSA-L 0.000 description 2
- 208000036626 Mental retardation Diseases 0.000 description 2
- 210000003754 fetus Anatomy 0.000 description 2
- 239000011521 glass Substances 0.000 description 2
- 230000003053 immunization Effects 0.000 description 2
- 238000000338 in vitro Methods 0.000 description 2
- 238000002360 preparation method Methods 0.000 description 2
- 229940037001 sodium edetate Drugs 0.000 description 2
- UPLPHRJJTCUQAY-WIRWPRASSA-N 2,3-thioepoxy madol Chemical compound C([C@@H]1CC2)[C@@H]3S[C@@H]3C[C@]1(C)[C@@H]1[C@@H]2[C@@H]2CC[C@](C)(O)[C@@]2(C)CC1 UPLPHRJJTCUQAY-WIRWPRASSA-N 0.000 description 1
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 1
- WHUUTDBJXJRKMK-VKHMYHEASA-N L-glutamic acid Chemical compound OC(=O)[C@@H](N)CCC(O)=O WHUUTDBJXJRKMK-VKHMYHEASA-N 0.000 description 1
- 201000005505 Measles Diseases 0.000 description 1
- 208000005647 Mumps Diseases 0.000 description 1
- 241000283973 Oryctolagus cuniculus Species 0.000 description 1
- 241000709664 Picornaviridae Species 0.000 description 1
- 229940061607 dibasic sodium phosphate Drugs 0.000 description 1
- 239000003085 diluting agent Substances 0.000 description 1
- 210000001840 diploid cell Anatomy 0.000 description 1
- 201000010099 disease Diseases 0.000 description 1
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 1
- BNIILDVGGAEEIG-UHFFFAOYSA-L disodium hydrogen phosphate Chemical compound [Na+].[Na+].OP([O-])([O-])=O BNIILDVGGAEEIG-UHFFFAOYSA-L 0.000 description 1
- 229930195712 glutamate Natural products 0.000 description 1
- 230000028993 immune response Effects 0.000 description 1
- 208000015181 infectious disease Diseases 0.000 description 1
- 230000005764 inhibitory process Effects 0.000 description 1
- 239000007924 injection Substances 0.000 description 1
- 238000002347 injection Methods 0.000 description 1
- 238000007918 intramuscular administration Methods 0.000 description 1
- 210000003292 kidney cell Anatomy 0.000 description 1
- 230000008774 maternal effect Effects 0.000 description 1
- 238000000034 method Methods 0.000 description 1
- 208000004141 microcephaly Diseases 0.000 description 1
- 229940111688 monobasic potassium phosphate Drugs 0.000 description 1
- 235000019796 monopotassium phosphate Nutrition 0.000 description 1
- 208000010805 mumps infectious disease Diseases 0.000 description 1
- 229960005030 other vaccine in atc Drugs 0.000 description 1
- 210000002826 placenta Anatomy 0.000 description 1
- 239000001267 polyvinylpyrrolidone Substances 0.000 description 1
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 description 1
- 229920000036 polyvinylpyrrolidone Polymers 0.000 description 1
- GNSKLFRGEWLPPA-UHFFFAOYSA-M potassium dihydrogen phosphate Chemical compound [K+].OP(O)([O-])=O GNSKLFRGEWLPPA-UHFFFAOYSA-M 0.000 description 1
- 229960003131 rubella vaccine Drugs 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- 238000007920 subcutaneous administration Methods 0.000 description 1
- 239000006228 supernatant Substances 0.000 description 1
- 229940124856 vaccine component Drugs 0.000 description 1
- 230000003612 virological effect Effects 0.000 description 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K39/00—Medicinal preparations containing antigens or antibodies
- A61K39/12—Viral antigens
- A61K39/20—Rubella virus
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K39/00—Medicinal preparations containing antigens or antibodies
- A61K39/12—Viral antigens
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K39/00—Medicinal preparations containing antigens or antibodies
- A61K39/12—Viral antigens
- A61K39/245—Herpetoviridae, e.g. herpes simplex 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
- A61K2039/70—Multivalent vaccine
-
- 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
- C12N2710/00—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA dsDNA viruses
- C12N2710/00011—Details
- C12N2710/16011—Herpesviridae
- C12N2710/16111—Cytomegalovirus, e.g. human herpesvirus 5
- C12N2710/16134—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
- C12N2770/36011—Togaviridae
- C12N2770/36211—Rubivirus, e.g. rubella virus
- C12N2770/36234—Use of virus or viral component as vaccine, e.g. live-attenuated or inactivated virus, VLP, viral protein
Landscapes
- Life Sciences & Earth Sciences (AREA)
- Health & Medical Sciences (AREA)
- Virology (AREA)
- Pharmacology & Pharmacy (AREA)
- Immunology (AREA)
- Medicinal Chemistry (AREA)
- Microbiology (AREA)
- Mycology (AREA)
- Chemical & Material Sciences (AREA)
- Epidemiology (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Medicinal Preparation (AREA)
- Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
Description
"Vaccins bivalents contre la rubéole et la cytomégalie" <EMI ID=1.1>
La présente invention concerne des compositions vaccinales bivalentes contre la rubéole et la maladie des inclusions cyromégaliques ou cytomégalie.
On sait que le virus de la rubéole peut traverser le placenta
<EMI ID=2.1>
le nouveau-né.
L'existence d'anticorps maternels circulants contre le virus de la rubéole peut prévenir cette grave menace et divers vaccins ont été développés depuis plusieurs années, tant sous forme de vaccins monovalents que sous forme de combinaison à d'autres vaccins tels les vaccins contre la rougeole ou contre les oreillons.
Comme exemples de vaccins atténués contre la rubéole on peut
<EMI ID=3.1>
souche HPV 77 DE5 ou la souche CENDEHILL�.
Cependant le virus de la rubéole n'est pas le seul virus capable de provoquer des ravages chez le foetus. En effet, le virus de la maladie des inclusions cytomégaliques -également
<EMI ID=4.1>
cas d'arriération mentale et de microcéphalie d'origine virale chez le nouveau-né; on escime que parmi les nouveau-nés excrétant le virus (de 1 à 4 % de la totalité des nouveau-nés), 5 à 15 % présentent des caractéristiques d'arriération mentale et que
30 à 45 % des femmes en âge d'être mères ne possèdent pas
<EMI ID=5.1>
C'est pourquoi on étudie actuellement dans plusieurs pays l'innocuité et l'efficacité de vaccins contre la cytomégalie. Des
<EMI ID=6.1>
125 (Jupt M et coll Infection _3 : 111-4 1975) et une ?ouche vacci-
<EMI ID=7.1>
1-5,1974). Comme chacun des vaccins contre la rubéole et contre la cytomégalie vise le même but -la protection du foetus- et s'administre par la même voie, il est intéressant de pouvoir administrer simultanément les deux vaccins sous la forme d'un vaccin combiné et plus particulièrement sous la forme d'un vaccin combiné vivant. De plus, l'utilisation de vaccins combinés exige un personnel médical moins important et des injections moins fréquentes que ne l'exige l'utilisation de vaccins monovalents. Certains'travaux in vitro
ont montré qu'il existe des possibilités d'interférence entre le
CMV et des virus comme des myxovirus, des arbovirus, des picorna-
<EMI ID=8.1>
<EMI ID=9.1>
démontré que le virus de la rubéole provoque -in vitro- des interférences avec des virus hétérologues tels les picornavirus,
les myxovirus et les arbovirus (Parkman P.D. et coll., J. Immunology
<EMI ID=10.1>
<EMI ID=11.1>
de procéder à des essais préliminaires établissant le facteur d'interférence éventuel pour la combinaison envisagée.
Nous avons trouvé que dans le cas d'un vaccin vivant contre
la rubéole combiné à un vaccin vivant contre la cytomégalie, l'administration simultanée des deux virus n'affecte pas la réponse immunitaire à chaque composant vaccinal.
Dès lors, l'invention consiste en un vaccin combiné vivant contre la rubéole et la cvtomégalie contenant au moins les quantités de virus atténués de la rubéole et de CMV correspondant à la quantité immunisante de chacun desdits virus considérés séparément, la quantité de virus de la rubéole étant de préférence d'au moins
<EMI ID=12.1>
Pour réaliser la présente invention, les virus atténués sont
cultivés séparément suivant les techniques habituelles et mélangés dans les proportions adéquates et le vaccin bivalent obtenu est de préférence lyophilisé après adjonction d'une composition stabilisatrice, comme il est bien connu dans la technique. Comme compositions stabilisatrices, on peut indiquer entr'autres celles qui sont à base d'albumine sérique humaine ou de polyvinylpyrroli done.
Etant donné que la stabilité in vitro du CMV est relativement moins bonne que celle du virus de la rubéole, les conditions de lyophilisation du vaccin bivalent sont celles requises pour la lyophilisation du CMV.
Comme indiqué plus haut, la souche de virus de la rubéole peut être une souche vaccinale quelconque connue de l'homme de l'art, par exemple la souche atténuée CENDEHILL� cultivée sur cultures primaires de cellules de rein de lapin et la souche de CMV peut être une souche vaccinale quelconque connue de l'homme de l'art, par exemple la souche atténuée TOWNE 125 cultivée sur la lignée de cellules diploïdes humaines Wi-38.
Lorsque le vaccin bivalent faisant l'objet de la présente invention est présenté sous forme lyophilisée, on le reconstitue au posent de l'emploi par addition d'eau ou de tout autre diluant
<EMI ID=13.1>
<EMI ID=14.1>
Le vaccin bivalent ainsi préparé est administré par voie intramusculaire ou sous-cutanée.
L'invention est illustrée ;:lais non limitée par les exemples
<EMI ID=15.1>
EXEMPLE 1
<EMI ID=16.1>
<EMI ID=17.1>
on ajoute le même volume d'une solution aqueuse de saccharose
<EMI ID=18.1>
dibasique de sodium (0,0072 M), glutamate de potassium (0,0049 M) et d'édétate de sodium (0,2 %) additionnée d'un pourcent d'albumine sérique humaine.
<EMI ID=19.1>
<EMI ID=20.1>
solution aqueuse de saccharose (200 g/1.) et de glutamate de potassium (30 g/l.).
Les deux préparations sont mélangées et le mélange est réparti dans des flacons de verre à raison de un millilitre de mélange par flacon pour constituer des doses unitaires administrables par voie intramusculaire ou sous-cutanée.
Une étude clinique effectuée sur 13 adultes sensibles à chacun des deux virus démontré l'apparition d'anticorps contre le virus de le rubéole -mis en évidence par le test d'inhibition de l'hémagglutinatior
<EMI ID=21.1>
6 à 8 semaines après l'administration du vaccin bivalent.
EXEMPLE 2
<EMI ID=22.1>
<EMI ID=23.1>
on ajoute le même volume d'une solution aqueuse de saccharose
(0,218 M), phosphate monobasique de potassium (0,0038 M), phosphate dibasique de sodium (0,0072 M), glutamate de potassium (0,0049 M) et d'édétate de sodium (0,2 %) additionée d'un pourcent d'albumine sérique humaine.
A 90 ml. de surnageant d'une culture primaire de cellules de
<EMI ID=24.1>
solution aqueuse de saccharose (200 g/l.) et de glutamate de
n <EMI ID=25.1>
Les deux préparations sont mélangées et le mélange est réparti dans des flacons de verre à raison de un millilitre par flacon et lyophilisé.
Après lyophilisation et bouchage hermétique, chaque flacon contient une dose unitaire de vaccin bivalent dont le titre est
<EMI ID=26.1>
virus de la rubéole,
Le vaccin est administré par voie intramusculaire ou souscutanée.
<EMI ID=27.1>
<EMI ID=28.1>
cytomégalie, caractérisée en.ce qu'elle contient au moins des quantités de virus atténué de la rubéole et de virus atténué de
la maladie des inclusions cytomégaliques correspondant à la quantité immunisante de chacun desdits virus considérés séparément.
"Bivalent vaccines against rubella and cytomegaly" <EMI ID = 1.1>
The present invention relates to bivalent vaccine compositions against rubella and cyomegalic inclusion disease or cytomegaly.
Rubella virus is known to cross the placenta
<EMI ID = 2.1>
the newborn.
The existence of circulating maternal antibodies against the rubella virus can prevent this serious threat and various vaccines have been developed for several years, both as monovalent vaccines and as a combination with other vaccines such as vaccines against rubella. measles or mumps.
Examples of attenuated rubella vaccines can be
<EMI ID = 3.1>
strain HPV 77 DE5 or strain CENDEHILL �.
However, the rubella virus is not the only virus capable of wreaking havoc on the fetus. This is because the cytomegalic inclusion disease virus - also
<EMI ID = 4.1>
cases of mental retardation and microcephaly of viral origin in newborns; it is estimated that among newborns shedding the virus (1 to 4% of all newborns), 5 to 15% have features of mental retardation and that
30 to 45% of women of childbearing age do not have
<EMI ID = 5.1>
Therefore, the safety and efficacy of cytomegaly vaccines are currently being studied in several countries. Of
<EMI ID = 6.1>
125 (Jupt M et al Infection 3: 111-4 1975) and a vaccine strain
<EMI ID = 7.1>
1-5,1974). As each of the vaccines against rubella and against cytomegaly has the same goal - the protection of the fetus - and is administered by the same route, it is advantageous to be able to administer the two vaccines simultaneously in the form of a combined vaccine and more particularly in the form of a combined live vaccine. In addition, the use of combination vaccines requires fewer medical personnel and less frequent injections than required by the use of monovalent vaccines. Some in vitro work
have shown that there are possibilities of interference between the
CMV and viruses such as myxoviruses, arboviruses, picorna-
<EMI ID = 8.1>
<EMI ID = 9.1>
demonstrated that the rubella virus causes -in vitro- interference with heterologous viruses such as picornaviruses,
myxoviruses and arboviruses (Parkman P.D. et al., J. Immunology
<EMI ID = 10.1>
<EMI ID = 11.1>
to carry out preliminary tests establishing the possible interference factor for the envisaged combination.
We have found that in the case of a live vaccine against
rubella combined with a live cytomegaly vaccine, simultaneous administration of the two viruses does not affect the immune response to each vaccine component.
Therefore, the invention consists of a combined live vaccine against rubella and cvtomegaly containing at least the amounts of attenuated rubella virus and CMV corresponding to the immunizing amount of each of said viruses considered separately, the amount of virus of the rubella is preferably at least
<EMI ID = 12.1>
To carry out the present invention, the attenuated viruses are
cultured separately according to the usual techniques and mixed in the appropriate proportions and the bivalent vaccine obtained is preferably lyophilized after addition of a stabilizing composition, as is well known in the art. As stabilizing compositions, mention may be made, among others, of those which are based on human serum albumin or on polyvinylpyrroli done.
Since the in vitro stability of CMV is relatively less good than that of rubella virus, the lyophilization conditions of the bivalent vaccine are those required for the lyophilization of CMV.
As indicated above, the rubella virus strain can be any vaccine strain known to those skilled in the art, for example the attenuated strain CENDEHILL � cultured on primary cultures of rabbit kidney cells and the CMV strain can be any vaccine strain known to those skilled in the art, for example the attenuated strain TOWNE 125 cultured on the human diploid cell line Wi-38.
When the bivalent vaccine which is the subject of the present invention is presented in lyophilized form, it is reconstituted at the point of use by adding water or any other diluent.
<EMI ID = 13.1>
<EMI ID = 14.1>
The bivalent vaccine thus prepared is administered intramuscularly or subcutaneously.
The invention is illustrated;: but not limited by the examples
<EMI ID = 15.1>
EXAMPLE 1
<EMI ID = 16.1>
<EMI ID = 17.1>
add the same volume of an aqueous solution of sucrose
<EMI ID = 18.1>
sodium dibasic (0.0072 M), potassium glutamate (0.0049 M) and sodium edetate (0.2%) with the addition of one percent human serum albumin.
<EMI ID = 19.1>
<EMI ID = 20.1>
aqueous solution of sucrose (200 g / l.) and potassium glutamate (30 g / l.).
The two preparations are mixed and the mixture is distributed in glass vials at a rate of one milliliter of mixture per vial to constitute unit doses which can be administered by the intramuscular or subcutaneous route.
A clinical study carried out on 13 adults sensitive to each of the two viruses demonstrated the appearance of antibodies against the rubella virus - demonstrated by the haemagglutinatior inhibition test
<EMI ID = 21.1>
6 to 8 weeks after administration of the bivalent vaccine.
EXAMPLE 2
<EMI ID = 22.1>
<EMI ID = 23.1>
add the same volume of an aqueous solution of sucrose
(0.218 M), monobasic potassium phosphate (0.0038 M), dibasic sodium phosphate (0.0072 M), potassium glutamate (0.0049 M) and sodium edetate (0.2%) plus a percent human serum albumin.
At 90 ml. supernatant from a primary culture of
<EMI ID = 24.1>
aqueous solution of sucrose (200 g / l.) and glutamate
n <EMI ID = 25.1>
The two preparations are mixed and the mixture is distributed in glass vials at the rate of one milliliter per vial and lyophilized.
After lyophilization and hermetic stoppering, each vial contains a unit dose of bivalent vaccine with a titre of
<EMI ID = 26.1>
rubella virus,
The vaccine is administered intramuscularly or subcutaneously.
<EMI ID = 27.1>
<EMI ID = 28.1>
cytomegaly, characterized in that it contains at least amounts of attenuated rubella virus and attenuated rubella virus
the disease of cytomegalic inclusions corresponding to the immunizing quantity of each of said viruses considered separately.
Claims (1)
Priority Applications (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| BE159475A BE832758A (en) | 1975-08-26 | 1975-08-26 | BIVALENT VACCINES AGAINST RUBELLA AND CYTOMEGALIA |
| FR7624951A FR2321899A1 (en) | 1975-08-26 | 1976-08-17 | Bivalent antiviral vaccine - esp made from attenuated Cendehill strain (rubella) and Towne 125 strain (cytomegaly) |
| GB3643576A GB1565658A (en) | 1975-08-26 | 1976-09-02 | Scaffolding structure such as stays scaffoldings and similar supports |
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| BE832758 | 1975-08-26 | ||
| BE159475A BE832758A (en) | 1975-08-26 | 1975-08-26 | BIVALENT VACCINES AGAINST RUBELLA AND CYTOMEGALIA |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| BE832758A true BE832758A (en) | 1976-02-26 |
Family
ID=25648803
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| BE159475A BE832758A (en) | 1975-08-26 | 1975-08-26 | BIVALENT VACCINES AGAINST RUBELLA AND CYTOMEGALIA |
Country Status (1)
| Country | Link |
|---|---|
| BE (1) | BE832758A (en) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO1999061637A1 (en) * | 1998-05-22 | 1999-12-02 | The University Of British Columbia | Gene sequences of rubella virus associated with attenuation |
-
1975
- 1975-08-26 BE BE159475A patent/BE832758A/en not_active IP Right Cessation
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO1999061637A1 (en) * | 1998-05-22 | 1999-12-02 | The University Of British Columbia | Gene sequences of rubella virus associated with attenuation |
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| Date | Code | Title | Description |
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| RE | Patent lapsed |
Owner name: SMITH KLINE - RIT Effective date: 19860831 |