EP0000677B1 - Vaccin du virus de la parainfluenza et son procédé de préparation - Google Patents

Vaccin du virus de la parainfluenza et son procédé de préparation Download PDF

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Publication number
EP0000677B1
EP0000677B1 EP78400058A EP78400058A EP0000677B1 EP 0000677 B1 EP0000677 B1 EP 0000677B1 EP 78400058 A EP78400058 A EP 78400058A EP 78400058 A EP78400058 A EP 78400058A EP 0000677 B1 EP0000677 B1 EP 0000677B1
Authority
EP
European Patent Office
Prior art keywords
virus
parainfluenza
vaccine composition
preparation
cultures
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.)
Expired
Application number
EP78400058A
Other languages
German (de)
English (en)
Other versions
EP0000677A1 (fr
Inventor
Eugene Bernard Buynak
Maurice Ralph Hilleman
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Merck and Co Inc
Original Assignee
Merck and Co Inc
Priority date (The priority date 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 date listed.)
Filing date
Publication date
Application filed by Merck and Co Inc filed Critical Merck and Co Inc
Publication of EP0000677A1 publication Critical patent/EP0000677A1/fr
Application granted granted Critical
Publication of EP0000677B1 publication Critical patent/EP0000677B1/fr
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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
    • A61K39/155—Paramyxoviridae, e.g. parainfluenza 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
    • A61K2039/51—Medicinal preparations containing antigens or antibodies comprising whole cells, viruses or DNA/RNA
    • A61K2039/525—Virus
    • A61K2039/5254—Virus avirulent or attenuated
    • 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
    • C12N2760/00—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA ssRNA viruses negative-sense
    • C12N2760/00011—Details
    • C12N2760/18011—Paramyxoviridae
    • C12N2760/18611—Respirovirus, e.g. Bovine, human parainfluenza 1,3
    • C12N2760/18634—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
    • C12N2760/00—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA ssRNA viruses negative-sense
    • C12N2760/00011—Details
    • C12N2760/18011—Paramyxoviridae
    • C12N2760/18711—Rubulavirus, e.g. mumps virus, parainfluenza 2,4
    • C12N2760/18734—Use of virus or viral component as vaccine, e.g. live-attenuated or inactivated virus, VLP, viral protein

Definitions

  • the invention is concerned with the adaptation and propagation of parainfluenza type 3 in tissue cultures prepared from embryonated hens' eggs. More particularly, this invention is directed to the development of live virus vaccines against the parainfluenza group of agents following serial passage in chick embryo tissue culture. This procedure involves the steps of
  • Isolation and adaptation of parainfluenza virus can be accomplished in chick embryo tissue culture using virus previously propagated in another kind of cell culture, such as monkey kidney or a combination of monkey kidney and embryonated hens' eggs.
  • Isolation in the above-mentioned cell cultures can be from clinical material (e.g. throat swab).
  • Incubation of infected cultures can be carried out at any temperature between about 30° and about 38°C, preferably at 30-34°C (optimal 32°C) or at 35 to 38°C (optimal 36°C). From about 3 to about 20 serial passages may be employed to attenuate the virus.
  • Parainfluenza virus type 3 is isolated and adapted by at least 1 passage in monkey kidney cell culture.
  • the virus which has been established in A to be parainfluenza virus is added to glass bottles containing chick embryo tissue cultures prepared from minced and trypsinized approximately ten-day-old chick embryos.
  • the culture medium may be any of those which support cell growth and this may, for example, be the known medium 199 to which calf serum has been added.
  • the infected cell cultures are incubated in successive passages at 30-38°C and preferably at 30-34°C (optimal 32°C) and 35­38°C (optimal 36°C). During these passages the virus is replicated in large amount and becomes attenuated.
  • the parainfluenza virus harvested after this repeated serial passage is found to be non- pathogenic for monkeys and rodents, to cause little or no clinical reactions in human recipients, and to evoke a satisfactory level of neutralizing antibody.
  • the virus infectivity is stabilized by a suitable stabilizer such as sucrose, phosphate, glutamine, human albumin, or mixtures thereof.
  • a suitable stabilizer such as sucrose, phosphate, glutamine, human albumin, or mixtures thereof.
  • the virus pool is subdivided and filled into appropriate vials for use.
  • the product can be stored frozen or preferably dried from the frozen state and kept free of moisture.
  • the inoculum is parainfluenza virus type 3 which is obtained as described in A above after 2 passages in grivet monkey kidney cell culture and 9 passages in chick embryo tissue culture.
  • the washed tissue is trypsinized at 36°C using 0.25% trypsin (Difco 1:250) in tris saline buffer for approximately two hours.
  • the trypsin-cell suspension is harvested through two thicknesses of sterile cheese cloth and centrifuged at 1500 rpm for five minutes.
  • Growth medium consists of medium 199 (Morgan, J. F., Morton, H. J., and Parker, R. C., Proc. Soc. Exp. Biol. and Med., 73: 1-8, 1950) containing 2% unheated fetal calf serum and 50 mcg/ml neomycin. Bottle cultures are planted at a concentration of 700,000 viable cells per milliliter. Following incubation at 36°C for 48 to 72 hours, bottle cultures can be used for serial passage or vaccine preparation.
  • Chick embryo tissue cultures are prepared in glass bottles using medium 199 containing 2% unheated fetal calf serum as growth medium. Three to four days post-planting, the growth medium is decanted and the cultures inoculated with 5.0-10.0 ml of undiluted or diluted seed virus per bottle. Following an adsorption period of one hour at 30-34°C, 70 milliliters of medium 199 containing 2% a gamma calf serum is added to each bottle, and re-incubated at 30-34°C. Three to four days post- seeding, the bottle cultures are washed four times with Hanks' BSS, 100 milliliters per wash.
  • Appropriate harvest or harvests are selected following completion of infectivity titrations.
  • the selected material is removed from the freezer and thawed.
  • a sample is removed for control and safety testing.
  • the remaining fluid is clarified and a sample removed for monkey safety testing.
  • Appropriate additional stabilizer, as mentioned above, is added to the remaining fluid.
  • the fluids are distributed into individual vials and lyophilized. Following the lyophilization cycle the vials are capped, sealed and retained for reconstitution as a vaccine by the addition of sterile water (Water for Injection, U.S.P.).
  • the potency of the product is based on in- fectivi t y titrations in grivet monkey kidney cell cultures.

Landscapes

  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Virology (AREA)
  • Mycology (AREA)
  • Epidemiology (AREA)
  • Immunology (AREA)
  • Medicinal Chemistry (AREA)
  • Microbiology (AREA)
  • Veterinary Medicine (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Chemical & Material Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Pulmonology (AREA)
  • Micro-Organisms Or Cultivation Processes Thereof (AREA)
  • Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)

Claims (6)

1. Procédé de préparation d'un virus parainfluenza immunogène type 3 vivant, caractérise en ce qu'il implique d'isoler et d'adapter le virus par au moins un passage dans une culture cellulaire de rein de singe et une série de passages du virus, d'environ 3 à environ 20 fois, dans une culture cellulaire d'embryon de poulet.
2. Procédé selon la revendication 1, caractérisé en ce que l'isolement et l'adaptation s'effectuent à une température d'environ 30°C à environ 38°C.
3. Composition de vaccin contre le virus paràinfluenza, caractérisée en ce qu'elle comprend un virus obtenu par le procédé selon l'une des revendications 1 ou 2 avec un stabilisateur viral.
4. Composition de vaccin selon la revendication 3, caractérisée en ce que ledit stabilisateur comprend du saccharose, du phosphate, de la glutamine ou de l'albumine humaine, ou leurs mélanges.
5. Composition de vaccin selon l'une des revendications 3 ou 4, caractérisée en ce qu'elle est à l'état congelé.
6. Composition de vaccin selon l'une des revendications 3 ou 4, caractérisée en ce qu'elle est à l'état lyophilisé.
EP78400058A 1977-07-22 1978-07-12 Vaccin du virus de la parainfluenza et son procédé de préparation Expired EP0000677B1 (fr)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
US81795577A 1977-07-22 1977-07-22
US817955 1977-07-22

Publications (2)

Publication Number Publication Date
EP0000677A1 EP0000677A1 (fr) 1979-02-07
EP0000677B1 true EP0000677B1 (fr) 1981-08-05

Family

ID=25224287

Family Applications (1)

Application Number Title Priority Date Filing Date
EP78400058A Expired EP0000677B1 (fr) 1977-07-22 1978-07-12 Vaccin du virus de la parainfluenza et son procédé de préparation

Country Status (9)

Country Link
EP (1) EP0000677B1 (fr)
JP (1) JPS5444015A (fr)
DE (1) DE2860895D1 (fr)
DK (1) DK326878A (fr)
EG (1) EG14362A (fr)
ES (1) ES471766A1 (fr)
IT (1) IT1105533B (fr)
PT (1) PT68284A (fr)
ZA (1) ZA784161B (fr)

Families Citing this family (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4215107A (en) * 1978-12-29 1980-07-29 Merck & Co., Inc. Parainfluenza virus vaccine and its preparation
DE3852918T2 (de) * 1987-09-28 1995-07-13 Beecham Inc TGEV-Virus vom Schwein als Impfstoff für Hunde.

Family Cites Families (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JPS5317049B2 (fr) * 1972-08-25 1978-06-06

Also Published As

Publication number Publication date
JPS5444015A (en) 1979-04-07
PT68284A (en) 1978-08-01
IT7850293A0 (it) 1978-07-13
DK326878A (da) 1979-01-23
ES471766A1 (es) 1979-10-01
EP0000677A1 (fr) 1979-02-07
DE2860895D1 (en) 1981-11-05
ZA784161B (en) 1980-02-27
EG14362A (en) 1984-03-31
IT1105533B (it) 1985-11-04

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