CA2052459A1 - Vaccinal association against infective pathogenic agents - Google Patents

Vaccinal association against infective pathogenic agents

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Publication number
CA2052459A1
CA2052459A1 CA 2052459 CA2052459A CA2052459A1 CA 2052459 A1 CA2052459 A1 CA 2052459A1 CA 2052459 CA2052459 CA 2052459 CA 2052459 A CA2052459 A CA 2052459A CA 2052459 A1 CA2052459 A1 CA 2052459A1
Authority
CA
Canada
Prior art keywords
virus
valency
vaccinal
glycoproteins
antigenic
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.)
Abandoned
Application number
CA 2052459
Other languages
French (fr)
Inventor
Patrick Biront
Maurice Pensaert
Joris Vandeputte
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.)
Boehringer Ingelheim Animal Health France SAS
Original Assignee
Individual
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
Family has litigation
First worldwide family litigation filed litigation Critical https://patents.darts-ip.com/?family=9400808&utm_source=google_patent&utm_medium=platform_link&utm_campaign=public_patent_search&patent=CA2052459(A1) "Global patent litigation dataset” by Darts-ip is licensed under a Creative Commons Attribution 4.0 International License.
Application filed by Individual filed Critical Individual
Publication of CA2052459A1 publication Critical patent/CA2052459A1/en
Abandoned legal-status Critical Current

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Classifications

    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K39/00Medicinal preparations containing antigens or antibodies
    • A61K39/12Viral antigens
    • A61K39/245Herpetoviridae, e.g. herpes simplex virus
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K39/00Medicinal preparations containing antigens or antibodies
    • A61K39/12Viral antigens
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K39/00Medicinal preparations containing antigens or antibodies
    • A61K39/385Haptens or antigens, bound to carriers
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K39/00Medicinal preparations containing antigens or antibodies
    • A61K2039/51Medicinal preparations containing antigens or antibodies comprising whole cells, viruses or DNA/RNA
    • A61K2039/525Virus
    • A61K2039/5254Virus avirulent or attenuated
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K39/00Medicinal preparations containing antigens or antibodies
    • A61K2039/55Medicinal preparations containing antigens or antibodies characterised by the host/recipient, e.g. newborn with maternal antibodies
    • A61K2039/552Veterinary vaccine
    • CCHEMISTRY; METALLURGY
    • C12BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12NMICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N2710/00MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA dsDNA viruses
    • C12N2710/00011Details
    • C12N2710/16011Herpesviridae
    • C12N2710/16711Varicellovirus, e.g. human herpesvirus 3, Varicella Zoster, pseudorabies
    • C12N2710/16734Use of virus or viral component as vaccine, e.g. live-attenuated or inactivated virus, VLP, viral protein

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

Abstract

ABSTRACT

A VACCINAL ASSOCIATION AGAINST INFECTIVE
PATHOGENIC AGENTS

The vaccinal association against a pathogenic agent, for instance, a virus belonging to the animal or human herpes family, comprises a first valency comprising said pathogenic agent or virus in the attenuated living state or a recombinant expressing antigenic glycoproteins of said pathogenic agent or virus and a second valency comprising antigenic envelope or wall glycoproteins of said pathogenic agent or virus.
The two valencies may be either mixed together in a ready to use form, or to be extemporaneously mixed, or separated for a concomitant and separated administration.

Description

~ ~ ~ 2 i~ ~ ~

NEW VACCINAL ASSOCIATIONS

This invention relates to new vaccinal associations against viral, bacterial and parasitic pathogenic agents.
Generally, in the fields of the preparation of human and veterinary vaccines, one tries to prepare purified, or sub-unit, vaccines, made up of one or several immunogenic agents of the same kind from an infective pathogenic agent, or even only from the immunogenic agent's antigenic determinant, so as to obtain a well-defined protecting immune response and also to eliminate lesser known or toxic constituents.
As to vaccine associations, they generally aim to unit valencies from heterologuous pathogenic agents, or at least from different serotypes, so as to broaden the protective spectrum, this method being also used in the case of recombinant living vaccines.
True, in some isolated cases, it has been suggested to potentiate a sub-unit vaccine with : :

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concomitantly administrating a small amount of the whole pathogenic agent.
W.G. LAVER and R.G. WEBSTER (Virology 69, 511-522, 1976) have shown, for the influenza virus on hamsters and mice the potentiation of the immune response through concomitant injection of the untouched whole virus and the neuraminidase - hemagglutinin sub-unit vaccine or through injection of the untouched virus one hour before that of the same sub-unit vaccine.
R.G. WEBSTER et al. (The Journal of Immunology, Vol. 118, N 6, Decernber 1977, pp. 2073-2077) later showed on hamsters and men the potentiating effect of adding the inactivated influenza virus to the neuraminidase-hemagglutinin sub-unit vaccine.
This virus is the whole inactivated influenza virus, and the amount of whole pathogenic agent is small and aimed at potentientating the protecting effect of the sub-unit vaccine.
This invention has now shown in a surprising way that in the case of pathogenic agents which are very far from the influenza virus, such as notably the herpesviridae, the association of an envelope or wall sub-unit vaccine, i.e. immediately or easily apparent immunogenic agents Of the same pathogenic agents, greatly reinforces the efficiency of the vaccination, and that this feature extends to many pathogenic agents, including those belonging to widely different groups such as viruses, bacteria and parasitic agents, notably protozoa.
Aim of the invention is to significantly reinforce the efficiency of a vaccination against infectious diseases in animal and man.
Aim of this invention is thus a vaccinal ^, . :
... . .

, . . . ~ , ,. . :............... . -, ' ~'~ '.'' ''; ~';; .,, ',,, association comprising a first valency comprising an attenuated living microbial agent or a recombinant expressing antigenic proteins or glycoproteins of said agent, and a second valency comprising one or several antigenic envelope or wall glycoproteins, or an antigenic structural protein, notably of the same serotype.
By microbial agent, in the sense of the invention, is understood a virus, a bacterium, or a parasitic agent belonging to a pathogenic species and for which already exists, or may be produced, a living or inactivated form (deleted or not) which is immunogenic, and at least partially protecting, or else for which there are, or there may be built, nucleotide sequences which may be inserted in a recombinant heterologuous microorganism to be used as a vaccine and expressing antigenic proteins or glycoproteins which are at least partially protecting and encoded by such a sequence.
Among viral agents, one may notably mention, besides herpes viruses, parvoviruses, coronaviruses, human, porcine or equine influenza viruses, the polio-myelitls virus and the rabies viruses.
Among bacteria one may notably mention Brucella.
Among heterologuous microorganisms, one may notably mention pox-viruses, for instance vaccine or aviary pox-viruses, and herpes-viruses.
One must understand that in this invention the second valency generally comes from the same serotype (when different serotypes exist) as the agent yielding the first valency, but that in some .
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: .: :

2~2~

cases, serotypes may differ when it is avered that there is an efficient cross protection between sero-types.
The invention notably concerns a human or animal herpes vaccinal association comprising a first valency including the herpes virus in question in the attenuated living state (deleted or not deleted) or a recombinant expressing antigenic glycoproteins of said virus, and a second valency comprising one or several antigenic envelope glycoproteins, notably of the same serotype, and possibly other antigenic elements from said virus.
Among animal herpes, the invention notably relates to porcine, equine, bovine, feline and aviary herpes viruses.
Valencies may be made up of already known vaccines for men or animals. Vaccines based on atte-nuated living virus or vaccines based on viral sub~
units especially on envelope glycoproteins and nucleocapsides are thus notably known.
For Aujeszky's disease ~pseudo~abies), one may for instance mention Rhône Mérieux's Geskalone~ vaccine (France), which is an attenuated freeze-dried living vaccine in an aqueous or oily solvent, and the Geskypur~ vaccine, also from Rhône-Mérieux, which is a sub-unit vaccine, liquid or freeze-dried, with an adjuvant and made up of purified envelope glycoproteins.
According to the invention, this vaccinal association may be in the form of a unique preparation, or an extemporaneous mixture or with the two valencies separated for a separated concomitant administration.
By separated concomitant administration are meant injections in different points of the organism in . .
, , ~ ~ . . .
, . , . , ................................... ;- :
-: , 2 ~

a reduced time interval not extendin~ beyond a few hours and preferably a few minutes.
In the case of a ready for use preparation, the glycoprotein valency and the valency of the agent or attenuated virus or of recombinant are in a solution in an aqueous or oily solvent.
Preferably, in all other cases, the attenuated or recombinant valency is in the freeze-dried form and the glycoprotein valency is in the liquid or freeze-dried form.
The two valencies may be either freeze-dried and in admixture in the same flask to be later taken up with an aqueous or oily solvent, or the first valency may be taken up with the second valency initially in a liquid state in a aqueous or an oily medium, or again each of the valencies, freeze-dried and separated, may be taken up with a solvent of the same nature, aqueous or oily solvent, and then mixed together.
In the case of a separated concomitant administration, the valencies solvents may be aqueous, oily or respectively aqueous and oily.
The vaccinal association will preferably be presented in a unique package.
In the case of a unique preparation, the vaccinal association is presented in a ready to use form. Its administration may notably be made intramuscularly or intradermally.
In the case of an extemporaneous mixture, the two valencies are in the freeze-dried state, in the same flask and must be taken up with an aqueous or oily solvent, or each valency is separately presented and the two valencies must then be - - : : , ~- .. ' :
.;. . .
.. : : .:

2 ~

reunited on administration in the above described manner. The administration route is notably intra-muscular or intradermal.
In the case o~ a separated concomitant administration, the two valencies are presented separately. The glycoproteins valency may be ready to use or, like the first valency, may be in a freeze-dried form and must then be dissoluted before use. The administration route is notably intramuscular or intradermal for the valency including the attenuate agent or virus or a recombinant whereas, for the other valency, the administration route may be intrader~al, intramuscular or subcutaneous.
As an herpes veterinary association, one may mention for instance the Geskalone~-Geskypur~
association.
Naturally, the inventive association relates to all known attenuated or glycoprotein sub-unit vaccines. For equine, bovine, feline, and aviary herpes (including laryngotracheitis), attenuated living vaccines are already known and one may mention, as examples, the following sub-unit vaccines :
- equine vaccine : PNEUMEQUINE~
(Rhône Mérieux), an equine rhinopneumonitis vaccine ;
- bovine vaccine : IBEPUR~ (Rhône Mérieux), a bovine infectious rhinotracheitis vaccine ;
- feline vaccine : CORIFELIN~ or LEUCORIFELIN~
(Rhône Mérieux), feline rhinotracheitis virus vaccine ;
- aviary vaccine : in~ectious laryngotrachei~is.
The invention also relates to a vaccination proeess, notably against human or animal herpes viruses, . .

comprising the concomitant administration of the two above described valencies, mixed or separated, via the appropriate above mentioned administration route.
The invention will now be described more in detail with the help of embodiment examples and in .vivo. assay.
I. ASSAY
18 pigs were vaccinated against pseudorabies disease. These pigs were issued from sows which were vaccinated with the TOLVID vaccine (an attenuated vaccine deleted for gX) (twice a year). The protocol was the following :
- - 6 non-vaccinated pigs were used as control, - 6 pigs were vaccinated once with the Bartha strain as taken up in an oil-in-water Solvay adjuvant, the vaccine title being 105-5 CCID.50 per doses, - 6 pigs were vaccinated once with a GESKALONE gI-dose with a title of 105 5 CCID.50 per doses, taken up in a 2 ml GES~YP~R.
All these pigs wer con~ined together and 4 weeks after vaccination, they were all challenged by the oronasal route with 105 5 CCID.50, this dose being administrated thrice during 24 hours .
Serological results (seroneutralizing antibodies) :
- the control animals remain negative until the challenge : title < 2, - the animals which were vaccinated with the Bartha have an average title at the challenge time between 4 and 16, .: . ~ .' ''.,. ''' ' ' - 2 ~3 ~ 2 ~

- animals which were vaccinated with GESKYP~R/
GESKALONE :
1 animal : title 4.
1 animal : title 32 4 animals: titles 96.
Challenge :
Viral excretion parameter Duration Title Number of excreting animals control 5/6 days - all animals Bartha 2/3 days 1o2 to 3 4 out of 6 GESKYPUR/
GESKALONE 1 day hardly 2 out of 6 noticeable One thus obtains exceptional serological titles and challenge results.
II. EXAMPLES
1/ A unique preparation is carried out with a Geskalone dose taken up with 2 ml Geskypur.
This preparation is ready to use and may be adminis-trated via an intramuscular or intradermal route.
2/ One dose freeze-dried Geskalone and one dose ready to use Geskypur are put together in an unique package. At the time of administration, Geskalone is taken up with Geskypur. Administration is made intramuscularly or intradermally.
3/ Same as 2/ but Geskalone is taken up with an appropriate aqueous or oily solvent and the two valencies are concomitantly and separatedly admi-nistrated vla an intradermal or intramuscular route, ` ;' . :' ~ '::
. ~, ', ,. ' ,'- '. ~
, 2 ~

or via a subcutaneous route for Geskypur.
With the intradermal route, the two dose volumes are preferably 0.2 ml for each valency or for the two united valencies.
For the breeding pigs a primo-vaccination is for instance provided with two injections at 3 or 4 week 's intervals with boosters every six months, . , .
;, . .
. ~

.

Claims (17)

1. A vaccinal association against an infective disease, characterized in that it comprises a first valency comprising an attenuated living microbia 1 agent or a recombinant expressing antigenic proteins or glycoproteins of said agent, and a second valency comprising one or several antigenic envelope or wall glycoproteins or an antigenic structural protein, notably of the same serotype.
2. An association according to claim 1, characterized in that the agent is chosen among viruses, bacteria, and parasites.
3. An association according to claim 2, characterized in that the agent is chosen among those for which an attenuated living form at least partially protecting or an at least partially protecting recombinant is known.
4. A vaccinal association directed against a virus belonging to the animal or human herpes virus family and comprising in an unique preparation a first valency comprising said virus in the attenuated living state or a re-combinant expressing antigenic glycoproteins of said virus and a second valency comprising antigenic envelope glycoproteins of said virus.
5. A vaccinal association according to claim 4, characterized in that the two valencies are extemporaneously mixed together.
6. A vaccinal association according to any of claims 2 and 3 directed against a virus belonging to the animal or human herpes virus family and separately comprising for concomitant administration, on the one hand a first valency comprising said virus in the attenuated living state or a recombinant expressing antigenic glycoproteins of said virus, and on the other hand, a second valency comprising antigenic envelope glycoproteins of said virus.
7. A vaccinal association as ready to use according to claim 4, characterized in that the two valencies are in solution in an aqueous or oily solvent.
8. A vaccinal association according to claim 5, characterized in that the two valencies are in a freeze-dried form and mixed together so as to be concomitantly taken up with an oily or aqueous solvent.
9. A vaccinal association according to claim 5, characterized in that first valency is freeze-dried and the second is a liquid, an that the first must be taken up in the second.
10. A vaccinal association according to claim 5, characterized in that each valency is freeze-dried and must be taken up with an aqueous or oily solvent of the same nature, then mixed with the other valency.
11. A vaccinal association according to claim 6, characterized in that the two valencies are freeze-dried and must be separately taken up in an aqueous or oily solvent.
12. A vaccinal association according to claim 6, characterized in that the second valency is liquid and ready to use, whereas the first valency is freezedried, and must be taken up with an aqueous or oily solvent.
13. A vaccinal association according to any of claim 4 to 12, characterized in that the above mentioned animal virus is a porcine, equine, bovine, feline or aviary herpes virus.
14. A vaccinal association according to claim 13, characterized in that the above mentioned virus is the pseudorabies virus.
15. A vaccinal association according to any of claims 1 to 14, characterized in that it is packaged in a unique conditioning.
16. Vaccination method against an infective disea-se, wherein it is administered concomitantly a first valency comprising an attenuated living microbial agent or a recom-binant expressing antigenic proteins or glycoproteins of said agent, and a second valency comprising one or several antigenic envelope or wall glycoproteins or an antigenic structural protein, notably of the same serotype.
17. Vaccination method against a virus belonging to the animal or human herpes virus family, wherein it is administered concomitantly a first valency comprising said virus in the attenuated living state or a recombinant expressing antigenic glycoproteins of said virus and a second valency comprising antigenic envelope glycoproteins of said virus.
CA 2052459 1990-10-01 1991-09-30 Vaccinal association against infective pathogenic agents Abandoned CA2052459A1 (en)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
FR9012073A FR2667245B1 (en) 1990-10-01 1990-10-01 VACCINE ASSOCIATION AGAINST INFECTIOUS PATHOGENS.
FR9012073 1990-10-01

Publications (1)

Publication Number Publication Date
CA2052459A1 true CA2052459A1 (en) 1992-04-02

Family

ID=9400808

Family Applications (1)

Application Number Title Priority Date Filing Date
CA 2052459 Abandoned CA2052459A1 (en) 1990-10-01 1991-09-30 Vaccinal association against infective pathogenic agents

Country Status (8)

Country Link
EP (1) EP0479627B1 (en)
JP (1) JPH0687759A (en)
KR (1) KR920007636A (en)
AT (1) ATE140153T1 (en)
CA (1) CA2052459A1 (en)
DE (1) DE69120761T2 (en)
ES (1) ES2091307T3 (en)
FR (1) FR2667245B1 (en)

Families Citing this family (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5976552A (en) * 1995-04-28 1999-11-02 Protein Sciences Corporation Virus vaccines
ZA978434B (en) * 1996-09-27 1998-03-26 Akzo Nobel Nv Inactivated vaccines.
WO1998046262A1 (en) * 1997-04-16 1998-10-22 Connaught Laboratories, Inc. Anti-influenza compositions supplemented with neuraminidase

Family Cites Families (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
ES2069574T3 (en) * 1988-08-01 1995-05-16 Akzo Nobel Nv VACCINE AGAINST PSEUDORRABIA VIRUS.

Also Published As

Publication number Publication date
KR920007636A (en) 1992-05-27
DE69120761T2 (en) 1996-12-12
FR2667245B1 (en) 1992-11-06
ATE140153T1 (en) 1996-07-15
EP0479627B1 (en) 1996-07-10
ES2091307T3 (en) 1996-11-01
EP0479627A1 (en) 1992-04-08
JPH0687759A (en) 1994-03-29
DE69120761D1 (en) 1996-08-14
FR2667245A1 (en) 1992-04-03

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Legal Events

Date Code Title Description
FZDE Discontinued