FR2652257A1 - PORTABLE PORCINE VACCINATION INSTALLATION. - Google Patents

Abstract

The portable device for vaccination of pigs comprises an apparatus for administration by jet of doses of approximately 0.2 ml, connected to a supply of vaccine composition having the corresponding concentration.

Description

2652257-

  The invention relates to a portable installation

  intended for pig vaccination.

  Several infectious diseases of the pig, such as Aujeszky's disease and swine flu in particular, have made it necessary in recent years to develop

  vaccines and therefore the establishment of vaccination programs

  tions. These programs include pig vaccination in

  fattening, which comes up against several difficulties.

  The first is the very high number of pigs on vac-

  ciner; vaccination, by injection with needle, is done

  either with animal restraint, which is costly to lose

  staff and in working time, ie without restraint, which

  makes inoculation of the vaccine random under good conditions

tions.

  The second difficulty resides in the fact that the

  majority of vaccines are administered intramuscularly

  milk, at the level of the loin of the pig. However, all parties involved in the pork sector and therefore, ultimately, the consumer, are entitled to expect a quality product and therefore in particular the absence of any reaction abnormality in the tissues of the inoculated region. Unfortunately, it must be noted that this objective has not always been achieved. As a result, numerous observations have made it possible to qualitatively determine the nature and importance of these local reactions (P. Vannier - Reports

  of Veterinary Medicine, 1986, 162 (1), 37-44). This bad

  This tolerance is especially remarkable with inactivated vaccines in oily adjuvants, even if real progress has been made recently with this type of vaccines (Brun A. et al., 9th Congress IPVS Barcelona, Spain, July 15/18

1986).

  The use of attenuated non-adjuvanted virus vaccines,

  intramuscularly, decreases this type of risk. However

  In both cases, it is necessary to carry out the inoculations under suitable hygienic conditions. We realize in fact that several barriers, linked to the nature of the vaccine and its conditions of use, in practice prevent the obtaining of maximum safety for this route of inoculation and for this type of animals. There is also still the risk of parallel transmission of infectious agents during serial vaccination using a

  needle on a large number of animals.

  Needle-less injection devices have been known for a long time, the principle of which is administration by jet under very high pressure. We can quote for example the "IMOJET" of the Mérieux Institute in human medicine as well as the "DERMOJET" for the vaccination against Myxomatosis

rabbit.

  However, it has never been proposed to apply this

  technique for pig vaccination.

  The object of the invention is to remedy the drawbacks encountered during the vaccination of pigs by the usual techniques (method of administration and volume of the administered dose) using inactivated vaccines or live attenuated vaccines, by providing an installation vaccination which provides protection by vaccination at least equal to that of previous processes, while ensuring safety preserving the quality of food presentation and avoiding parallel contamination. Another object of the invention is to provide a

  installation which also allows good vac-

  cination. The subject of the invention is a portable pig vaccination installation, in particular by the intradermal route, characterized in that it comprises a device for administration by jet of doses of approximately 0.2 ml, connected to

  a supply of vaccine composition having the concentration

corresponding tration.

  The applicant has discovered that the use of a

  jet associated with vaccine doses of approximately 0.2 ml

  was due to satisfactory vaccination efficacy and, compared to the usual administration methods, better safety and no transmission of

  infectious diseases from one animal to another.

  This installation also makes it possible to ensure vaccination.

  nation without restraint and without encountering the vagaries of the usual injection vaccination using a needle

lack of restraint.

  By vaccine composition is meant either a single valency in its excipient, or a mixture of several

  valences in their excipient. The invention relates in particular to

  live attenuated and inactivated vaccines.

  The supply of vaccine composition is

  preference provided by the original bottle containing the vac-

  cin in solution in the vicinity of the ejection head

of the administration device.

  The facility has proven particularly suitable for vaccinating pigs against the disease

  of Aujeszky and / or against swine flu.

  Another object of the invention is to provide vac-

  cinales intended to be administered using

  the installation according to the invention. The vac-

  cinales concerned by the invention, described in detail below, are in particular the following: - Live attenuated vaccines in aqueous solution or in a solvent of the oily adjuvant type: vaccine against

  Aujezky's disease for example; it may be possible-

  ment consisting of viral subunits and / or not containing the GI glycoprotein. - Vaccines inactivated as an oily adjuvant: vaccine against Aujeszky's disease (possibly in viral subunits and / or without the GI glycoprotein); vaccine

swine flu.

  - Associated vaccines, in particular against swine flu

and Aujeszky's disease.

  The invention will now be described in a nonlimiting manner using an example of an administration device according to the invention and using biological tests demonstrating the effectiveness of the installation according to the invention.

  for various vaccines taken by way of nonlimiting examples

tifs.

ADMINISTRATION APPARATUS

  The portable administration device comprises, in a housing provided with a handle, a chamber calibrated to 0.2 ml and a piston normally held in the retracted position.

  in the chamber by a spring secured to said piston.

  Provided by an appropriate means, the compression of the spring causes the displacement of the piston and therefore the aspiration of the dose of vaccine from a reservoir or

bottle attached to the case.

  Releasing the spring causes the piston to retract

and ejecting the dose.

  The device also includes a calibrated nozzle intended to calibrate the jet and a filtration device to avoid

  injection of any impurities.

  The jet pressure at the nozzle outlet can be

set at 100 bars.

BIOLOGICAL TRIALS

  Three types of 0.2 ml vaccine per dose have been tested: vaccines against Aujeszky's disease, a vaccine against swine flu, an associated vaccine against Aujeszky's disease and

swine flu.

  1. Vaccines against Aujeszky's disease 1.1: Attenuated vaccine The vaccine used is a live attenuated vaccine prepared in aqueous adjuvant using the strain Alfort 26 (A. Brun, è IPVS Congress Rio de Janeiro, 14/17 August 1988). The dose volume is 0.2 ml and the titer per dose is

greater than or equal to 10 DICC50.

  The vaccine can also be prepared using a solvent

oily playing the role of adjuvant.

  Experimental pigs weigh around 25 kg, without antibodies on the day of vaccination or from

of vaccinated mothers.

  The test strain is the NIA3 strain (J.B. Mc FERRAN, International Symposium on Immunity to Infections of the

  Respiratory System in Man and Animals, London 1974. Develop.

  biol. Standard., Vol. 28, p. 563-570 - Karger, Basel 1975) inoculated into pigs in a volume of 0.5 ml per nostril, 7/3 representing approximately 10 'DICC50-. Antibodies are titrated

  by seroneutralization and expressed in base log 10.

  A first experiment was carried out at the laboratory.

  roof on pigs born to unvaccinated mothers, and without

antibody, weighing 25 kg.

  pigs were vaccinated using the installation according to the invention inoculating under pressure 0.2 ml of vaccine intradermally. 3 unvaccinated control pigs remained in contact with the vaccinated animals. The animals underwent a virulent test 21 days after vaccination and blood samples are taken on days O and 21. The animals are weighed individually on the day of the test and

7 days after the event.

  A second experiment was carried out in breeding on pigs born to mothers vaccinated using an inactive vaccine. The animals were vaccinated at the start of fattening, at the age of 10 weeks, in the same way as during the first experiment. At the end of their economic life, 8 vaccinated pigs as well as 8 unvaccinated control pigs from the same farm and 9 control pigs with no Aujeszky antibody test underwent a virulent test according to

  the same modalities as during the first experiment.

  The serological and pig test results from the first experiment are noted in Table I. The vaccinated animals exhibit little or no seroconversion after intradermal vaccination. Following the test, 1 control pig died of Aujeszky's disease and all of the control pigs showed a significant weight loss, on average of 5.6 kg, while the

  vaccinated pigs have an average weight gain of 1.35 kg.

  Serological and test results from

  the second experiment are noted in Table II.

  This second experiment, on the economic life of fattening pigs, confirms the results obtained during the first experiment, that is to say little or no seroconversion after vaccination, but very different behavior from vaccinated pigs compared to pigs

  witnesses following the virulent test.

  It has thus been demonstrated in immediate immunity, 21 days, and in immunity duration of 3 months, the possibility, with the installation according to the invention, of immunizing the fattening pig against Aujeszky's disease by a single intradermal vaccination, using the strain

Alfort 26.

  Finally, another criterion taken into account to assess the protection conferred by vaccination is the study of

  viral excretion after viral testing, by swab-

nasal swabs.

  In Figure 1, we can see that unvaccinated pigs shed virus longer than pigs

  vaccinated intradermally or intramuscularly.

  1.2 Live attenuated vaccine (strain Alfort 26) without the GI glycoprotein The medical and sanitary prophylaxis of Aujeszky's disease involves the distinction between vaccinated and convalescent animals. This is possible thanks to the use of inactivated or attenuated vaccines for which one or more envelope glycoproteins have been eliminated from the virus. In this case, the suppression of the GI glycoprotein makes it possible to differentiate by serology the pigs vaccinated with this

  type of vaccine, convalescent pigs.

  The GI vaccine is prepared at. from the Alfort strain

  26 not containing the GI glycoprotein. The above tests

  after were performed intradermally with this vac-

  cin. Two groups of susceptible pigs were vaccinated intradermally, as two injections at 14 days

  interval, using the installation according to the invention.

  In one case, the lyophilized vaccine was resuspended

  with a conventional solvent - water for injection.

  In the other case, the lyophilized vaccine was resuspended with an oily adjuvant type solvent. The vaccinated animals were tested 19 days after booster vaccination with a group of unvaccinated control pigs. The protection criterion after test is the difference in relative daily average gain (GMQR) at day 7 after test,

  between vaccinated pigs and control pigs (C. Stellmann, Jour-

  nal of Biological Standardization (1989), 17, 17-27),

or the LG7 index.

  Tables III and IV demonstrate the very good protection

  tion conferred by this vaccine inoculated intradermally using the installation according to the invention, in the form of

two vaccine injections.

  1.3: Inactivated vaccine with viral subunits without the

GI glycoprotein.

  The vaccine is prepared from a strain of

  GI and gp63 free pseudo-rabies.

  The strain is grown on BHK21 cells. The virus is then inactivated with ethyleneimine, purified and treated with polyoxyethylene alcohol so as to extract the envelope glycoproteins. The proteins in the capsule are removed by ultracentrifugation. The supernatant, which is recovered, is a concentrated solution of purified glycoproteins.

  Sensitive pigs are vaccinated intrader-

  mique using the installation according to the invention, in a single injection and tested at the same time as control pigs 21 days later. The protection criterion is identical to that of test 1.2. In this case, the viral envelope glycoproteins are adjuvanted using an oily-type adjuvant identical to that of test 1.2. Table V shows that the vaccinated pigs have

satisfactory protection.

  2. H1N1 H3N2 swine flu vaccine.

  The purified inactivated vaccine of swine flu in oily adjuvant, of the same nature as that used for tests 1.2 and 1.3, was controlled in pigs at the rate of 2 injections 28 days apart using

the installation according to the invention.

  The criteria taken into account to measure the activity of

  this vaccine is post-vaccine serology - inhi-

  bant the haemagglutination (in log 10) - and the evolution of the weight of the pigs after virulent H1N1 test. The results

are shown in Table VI.

  The swine flu vaccine, in a volume of 0.2 ml, in 2 injections using the installation according to the invention,

  provides satisfactory protection.

  3. Combined vaccine against Aujeszky's disease and swine flu This association is made by mixing extemporaneously the live lyophilized vaccine of the disease

  of Aujeszky and the liquid inactivated influenza vaccine

  cine which is used as solvent for the former. The satisfactory activity of this combined vaccine was checked by the specific anti-Aujeszky and anti-swine flu antibodies H1H1 and H3N2, obtained following two injections one month apart using the installation.

  according to the invention, as indicated in Table VII.

  All the trials carried out have demonstrated excellent local tolerance, regardless of the vaccine used. Each injection results in the appearance of a

papule, visible to the naked eye.

TABLE I

  Seroneuantibodies - Weight of pigs (kg) tralising Day of day + 7 days D.0 D.2r proof

4 0.2 0.4 29 32

  pigs <0.2 4 0.2 30.5 31.5 vaccines <0.2 0.6 23 26

<0.2 0.4 24 25

<0.2 4 0.2 34.75 33.5

average 28.25 29.6 e.t. 4.32 3.43

4 0.2 <0.2 31 25.5

  pigs <02 <0.2 30 26.5 no <0.2 <0.2 28.5 22 * vaccinated z 0i2 <0.2 25.5 20

<0.2 0.2 33 26

average e.t. 29.6 24

2.52 2.55

* death at J. 6 e.t .: standard deviation

TABLE II

  Seroneutralizing antibodies Weight of pigs (kg) Pigs Day Day Difference J.0. test trial + 7 days 8 vaccinated 2 pigs <0.2 m = 89.5 m = 89.38 - 0.13 6 pigs: 0.46 SE = 8.67 SE = 8.53 m = 0 , 4 8 controls 8 pigs <0.2 m = 88.32 m = 85.38 - 2.94 farmed and = 5.68 ET = 6.16 1 dead on J.7 9 controls <0.2 < 0.2 m = 102 | m = 99 -3.22 of test e.t. = 8.74 ET = 10.25 1 death on J.6 (n (n

TABLE III

  Weight to Deadweight G M Q R%: Mode J. 33 J. 40 to: J.33 and J.40 Event

24.80 20.00 J.6 - 3.23

42.50 - 35.00 J.6 - 2.94

  Witnesses 29.00 25.50 - 1.72 test 36.00 27.00 J.7 - 3.57

37.00 32.00 J.6 - 2.25

  average 33.36 27.90 - 2.74 e.t. 6.24 5.22 0.67 variance 38.96 27.24 0.45 Pigs 25.20 27.50 1.30 vaccinated 33.00 32.00 - 0.43 (solvent 31.50 36.00 2, 04 aqueous) 35.00 27.00 - 3.27

42.50 42.50 0.00

  average 33.44 33.00 - 0.07 e.t. 5.59 5.77 1.83 variance 31.27 33.30 3.34

 G7 = 2.67

TABLE IV

  Weight to Deadweight GMQR% Terms at: J.33 J.40 J. 33 and 40 Event

24.80 20.00 J.6 - 3.23

42.50 35.00 J.6 -2.94

  Witnesses 29.00 25.50 - 1.72 trial 36.00 27.00 J.7 -3.57

37.00 32.00 J.6 - 2.25

  average 33.86 27.90 - 2.74 e.t. 6.24 5.22 0.67 variance 38.96 27.24 0.45 Pigs 33.00 35.00 0.87 vaccinated 35.70 35.50 - 0.08 (solvent 38.00 36.50 0, 56 oily) 45.00 46.50 0.45 average 37.93 38.38 0.17 and 4.45 4.72 0.54 variance 19.92 22.30 0.29

& G7 = 2.92

TABLE V

  Deadweight GMQR% J. 21 and Conditions J. 21 and

J.21 J.28 to: J.28

Test

26.50 20.50 J.5 - 4.53

51.00 47.00 - 1.12

  Witnesses 32.00 27.00 - 2.23 trial 31.00 30.00 - 0.46

42.50 39.00 - 1.18

  average 36.60 32.70 - 1.90 e.t. 8.91 9.30 1.43 variance 79.34 86.56 2.04

32.00 31.00 - 0.45

.00 31.00 0.48

  Pigs 34.00 31.00 - 1.26 vaccinated 27.00 28.50 0.79

29.50 32.00 1.21

  average 30.50 30.70 0.15 e.t. 2.37 1.17 0.89 variance 5.60 1.36 0.80

AG7 = 2.06

TABLE VI

  Antibody 14 days antcrps 14pe juice Weight of pigs after test

after recall.

  Difference Difference HlNl H3N2 J.0. J.3 J.3 - J.0 J.7 J.7 - J O

  2.10 1.8 56.00 60.00 4.00 61.00 5.00

  1.50 2.10 45.50 45.00 - 0.50 47.80 2.30

  pigs 2.10 3 35.50 35.50 0.00 41.40 2.90 vaccinated 1.20 1.8 no 2.10 2.7 proven average 1.80 2.28 46.67 47.83 1, 17 50.07 3.40 and 7.19 9.00 2.01 8.16 1.16 variance 51.72 81.06 4.06 66.60 1.34

  0.9 1.20 47.50 47.00 - 0.50 49.00 1.50

  0.9 1.20 53.00 50.00 - 3.00 53.00 0.00

  pigs 0.9 1.20 34.50 35.80 1.30 35.40 0.90 controls 0.9 1.20 no 0.9 1.20 proven average 0.9 1.20 45.00 44.27 - 0.73 45.80 0.80 and 7.76 6.11 1.76 7.53 0.62 variance 60.17 37.34 3.11 56.75 0.38

TABLE VII

  Antibody Antibody Swine Flu Aujeszky HlNl H3N2

1.7 1.20 2.10

1.7 2.40 2.40

1.7 2.10 2.10

  Pigs 1.9 1.50 2.10 vaccinated 1 2.10 2.10

1.9 2.10 2.40

1.7 1.50 2.40

1.4 2.10 2.10

1.2 1.50 2.10

1.9 1.80 2.40

  average 1.61 1.7 2.22 e.t. 0.29 0.38 0.15

0.5 0.9 1.20

0.2 0.9 1.20

0.2 0.9 1.20

  Pigs 0.2 0.9 1.20 controls 0.2 0.9 1.20

0.2 0.9 1.20

0.2 0.9 1.20

0.2 0.9 1.20

0.2 0.9 1.20

0.5 0.9 1.20

  average 0.26 0.90 1.20 e.t. 0.12 / /% of animals with positive nasal swab "g90 - Intradermal \ 0 \\ _.Intramuscular X _____ \ __ \ Controls Y

_% - -

o

, 7

  d.5 6 7 8 9 10 11 12 Days Chart 1

Claims (9)

  1. Portable pig vaccination installation, characterized in that it comprises an apparatus for administration by jet of doses of approximately 0.2 ml, connected to a supply of vaccine composition having the concentration corresponding tration.   2. Installation according to claim 1, characterized in that the supply of vaccine composition is ensured by the original bottle placed in the vicinity of the ejection head.   3. Vaccine composition intended to be administered to   using the installation according to any of the claims   cations 1 and 2, characterized in that they are vaccines living attenuated.   4. Vaccine composition intended to be administered to   using the installation according to any of the claims   cations 1 and 2, characterized in that they are inactivated vaccines. 5. A vaccine composition according to claim 3 or 4,   characterized in that it is a vaccine against mala- die d'Aujeszky.   6. Vaccine composition according to claim 5, characterized in that the vaccine against the disease   of Aujeszky is composed of viral subunits.   7. Vaccine composition according to claim 5 or 6, characterized in that the vaccine does not include the GI glycoprotein.   8. Vaccine composition according to claim 4, characterized in that it is a flu vaccine swine.   9. Vaccine composition intended to be administered to   using the installation according to any of the claims   cations 1 and 2, characterized in that it comprises a vac-   cin inactivated against swine flu by oily adjuvant and live attenuated vaccine against Aujeszky's disease, the inactivated vaccine adjuvant serving as a vaccine solvent living attenuated.