EP0420744A1 - Portable device for vaccination of pigs - 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

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. These programs include vaccination of fattening pigs, which faces several difficulties.

The first is the very high number of pigs to be vaccinated; vaccination, by injection with needle, is done either with restraint of the animals, which is costly in staff and in working time, or without restraint, which makes inoculation of the vaccine in good conditions uncertain.

The second difficulty lies in the fact that the majority of vaccines are administered intramuscularly, at the level of the back 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. It must unfortunately be noted that this objective has not always been achieved. As a result, many observations have allowed to qualitatively determine the nature and the importance of these local reactions (P. Vannier - Recueil de Médecine Vétérinaire, 1986,162 (1), 37-44). This poor tolerance is especially remarkable with vaccines inactivated as an oily adjuvant, even if real progress has been made recently with this type of vaccine (Brun A. et al., 9th Congress IPVS Barcelona, Spain, July 15/18 1986).

The use of non-adjuvanted attenuated virus vaccines, intramuscularly, reduces 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. In addition, there is always the risk of parallel transmission of infectious agents during mass 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 cite for example the "IMOJET" of the Mérieux Institute in human medicine as well as the "DERMOJET" for vaccination against Rabbit Myxomatosis.

However, it has never been proposed to apply this technique to the vaccination of pigs.

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 of vaccination which makes it possible to confer protection by vaccination at least equal to that of the previous processes, while ensuring a safety preserving the quality of food presentation and avoiding the contaminations parallel.

Another objective of the invention is to provide an installation which also allows good vaccination rates.

The subject of the invention is a portable installation for pig vaccination, in particular by the intradermal route, 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.

The applicant has discovered that the use of a jet device combined with vaccine doses of approximately 0.2 ml leads to satisfactory vaccination efficacy and, compared with the usual modes of administration, to better safety and no transmission of infectious diseases from one animal to another.

It has also been found that this installation provides, in an extremely reliable manner, an intradermal injection which shows great advantages in pigs.

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 vaccines and inactivated vaccines.

The supply of vaccine composition is preferably provided by the original bottle containing the vaccine in solution placed in the vicinity of the ejection head of the administration device.

The installation has proved particularly suitable for vaccinating pigs against Aujeszky's disease and / or against swine flu.

Another object of the invention is also vaccine compositions intended to be administered using the installation according to the invention. The vaccine compositions concerned by the invention, described in detail below, are in particular the following:
- Live attenuated vaccines in aqueous solution or in an oily adjuvant type solvent: vaccine against Aujezky's disease for example; it may possibly consist of viral subunits and / or not contain the GI glycoprotein.
- Inactivated vaccines in oily adjuvant: vaccine against Aujeszky's disease (possibly in viral subunits and / or without the GI glycoprotein); swine flu vaccine.
- 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.

ADMINISTRATION APPARATUS

The portable type 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.

Caused by an appropriate means, the compression of the spring causes the piston to move and therefore the aspiration of the dose of vaccine from a reservoir or vial fixed on the housing.

The release of the spring causes the piston to retract and the dose to be ejected.

The device also includes a calibrated nozzle intended to calibrate the jet and a filtration device to avoid the injection of possible impurities. Instead of a single nozzle, one can thus provide a group of nozzles, for example five, slightly spaced from each other.

The jet pressure at the outlet of the nozzle 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 swine flu vaccine,
. 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 Alfort 26 strain (A. Brun, 10th Congress I.P.V.S. Rio de Janeiro, August 14/17, 1988). The dose volume is 0.2 ml and the titer per dose is greater than or equal to 10⁵ DICC50.

The vaccine can also be prepared using an oily solvent acting as an adjuvant.

Experimental pigs weigh approximately 25 kg, without antibodies on the day of vaccination or from vaccinated mothers.

The test strain is the NIA3 strain (JB 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, representing approximately 10 ^7.3 DICC50. The antibodies are titrated by seroneutralization and expressed in base log 10.

A first experiment was carried out in the laboratory on pigs born from unvaccinated mothers, and without antibodies, weighing 25 kg.

5 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 0 and 21. The animals are weighed individually on the day of the test and 7 days after the test.

A second experiment was carried out in breeding on pigs born to mothers vaccinated using an inactivated 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 economic life, 8 vaccinated pigs as well as 8 unvaccinated control pigs from the same farm and 9 control pigs with an Aujeszky antibody test have undergone a virulent test in the same way as during the first experiment.

The serological and test results of pigs from the first experiment are noted in Table I.

Vaccinated animals show little or no seroconversion after intradermal vaccination. Following the test, 1 control pig died of Aujeszky's disease and all control pigs showed a significant weight loss, on average of 5.6 kg, while the vaccinated pigs have an average weight gain 1.35 kg.

The serological and pig 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 Alfort 26 strain.

Finally, another criterion taken into account to assess the protection conferred by vaccination is the study of viral excretion after a virulent test, by nasal swabs.

In graph 1, we can see that pigs not vaccinated animals shed virus longer than pigs injected intradermally or intramuscularly.

1.2 Live attenuated vaccine (strain Alfort 26) without 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 pigs vaccinated with this type of vaccine, convalescent pigs.

The GI vaccine is prepared from the Alfort 26 strain which does not contain the GI glycoprotein. The following tests were carried out intradermally with this vaccine.

Two groups of sensitive pigs were vaccinated intradermally, in the form of two injections 14 days apart, 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 post-trial protection criterion is the difference in relative daily average gain (GMQR) at day 7 after trial, between vaccinated and control pigs (C. Stellmann, Journal of Biological Standardization (1989), 17, 17-27), i.e. the ΔG7 index.

Tables III and IV demonstrate the very good protection 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 GI Glycoprotein.

The vaccine is prepared from a strain of pseudo-rabies virus free from GI and gp63.

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 intradermally 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 offer satisfactory protection.

2. H1N1 H3N2 swine flu vaccine.

The purified inactivated vaccine of swine flu in oily adjuvant, of the same kind as that used for tests 1.2 and 1.3, was controlled in pigs with 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 - antibody inhibiting hemagglutination (in log 10) - and the evolution of the weight of 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, gives satisfactory protection.

3. Combined vaccine against Aujeszky's disease and swine flu

This association is achieved by mixing extemporaneously the freeze-dried live vaccine of Aujeszky's disease and the liquid inactivated vaccine of porscine influenza which is used as solvent for the former.

The satisfactory activity of this combined vaccine was checked by 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 shown in Table VII.

TABLEAU III Modalité Poids à J. 33 Poids à J. 40 Mort à : G M Q R %: J.33 et J.40 Epreuve Témoins d'épreuve 24,80 20,00 J.6 - 3,23 42,50 35,00 J.6 - 2,94 29,00 25,50 - 1,72 36,00 27,00 J.7 - 3,57 37,00 32,00 J.6 - 2,25 moyenne 33,36 27,90 - 2,74 e.t. 6,24 5,22 0,67 variance 38,96 27,24 0,45 Porcs vaccinés (solvant aqueux) 25,20 27,50 1,30 33,00 32,00 - 0,43 31,50 36,00 2,04 35,00 27,00 - 3,27 42,50 42,50 0,00 moyenne 33,44 33,00 - 0,07 e.t. 5,59 5,77 1,83 variance 31,27 33,30 3,34 ΔG7 = 2,67 TABLEAU IV Modalités Poids à J.33 Poids à J.40 Mort à : GMQR %: J. 33 et 40 Epreuve Témoins d'épreuve 24,80 20,00 J.6 - 3,23 42,50 35,00 J.6 - 2,94 29,00 25,50 - 1,72 36,00 27,00 J.7 - 3,57 37,00 32,00 J.6 - 2,25 moyenne 33,86 27,90 - 2,74 e.t. 6,24 5,22 0,67 variance 38,96 27,24 0,45 Porcs vaccinés (solvant huileux) 33,00 35,00 0,87 35,70 35,50 - 0,08 38,00 36,50 - 0,56 45,00 46,50 0,45 moyenne 37,93 38,38 0,17 e.t. 4,45 4,72 0,54 variance 19,92 22,30 0,29 ΔG7 = 2,92 TABLEAU V Modalités Poids à Mort à : GMQR % J. 21 et J.28 J.21 J.28 Epreuve Témoins d'épreuve 26,50 20,50 J.5 - 4,53 51,00 47,00 - 1,12 32,00 27,00 - 2,23 31,00 30,00 - 0,46 42,50 39,00 - 1,18 moyenne 36,60 32,70 - 1,90 e.t. 8,91 9,30 1,43 variance 79,34 86,56 2,04 Porcs vaccinés 32,00 31,00 - 0,45 30,00 31,00 0,48 34,00 31,00 - 1,26 27,00 28,50 0,79 29,50 32,00 1,21 moyenne 30,50 30,70 0,15 e.t. 2,37 1,17 0,89 variance 5,60 1,36 0,80 ΔG7 = 2,06 TABLEAU VI Anticorps 14 jours après rappel Poids des porcs après épreuve H1N1 H3N2 J.0 J.3 Différence J.3 - J.0 J.7 Différence J.7 - J.0 porcs vaccinés 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 2,10 3 35,50 35,50 0,00 41,40 2,90 1,20 1,8 non éprouvés 2,10 2,7 moyenne 1,80 2,28 46,67 47,83 1,17 50,07 3,40 e.t. 7,19 9,00 2,01 8,16 1,16 variance 51,72 81,06 4,06 66,60 1,34 porcs témoins 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 0,9 1,20 34,50 35,80 1,30 35,40 0,90 0,9 1,20 non éprouvés 0,9 1,20 moyenne 0,9 1,20 45,00 44,27 - 0,73 45,80 0,80 e.t. 7,76 6,11 1,76 7,53 0,62 variance 60,17 37,34 3,11 56,75 0,38 TABLEAU VII Anticorps Anticorps Grippe porcine Aujeszky H1N1 H3N2 Porcs vaccinés 1,7 1,20 2,10 1,7 2,40 2,40 1,7 2,10 2,10 1,9 1,50 2,10 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 moyenne 1,61 1,7 2,22 e.t. 0,29 0,38 0,15 Porcs témoins 0,5 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 0,2 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 moyenne 0,26 0,90 1,20 e.t. 0,12 / /

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 Seroneutralizing antibodies Weight of pigs (kg) OJ J.21 Trial day + 7 days vaccinated pigs <0.2 0.4 29 32 <0.2 <0.2 30.5 31.5 <0.2 0.6 23 26 <0.2 0.4 24 25 <0.2 <0.2 34.75 33.5 average 28.25 29.6 and 4.32 3.43 unvaccinated pigs <0.2 <0.2 31 25.5 <0.2 <0.2 30 26.5 <0.2 <0.2 28.5 22 * <0.2 <0.2 25.5 20 <0.2 <0.2 33 26 average 29.6 24 and 2.52 2.55 * died at J. 6 and: standard deviation

Modality Weight at J. 33 Weight at J. 40 Death to: GMQR%: J.33 and J.40 Test Test Witnesses 24.80 20.00 J.6 - 3.23 42.50 35.00 J.6 - 2.94 29.00 25.50 - 1.72 36.00 27.00 J.7 - 3.57 37.00 32.00 J.6 - 2.25 average 33.36 27.90 - 2.74 and 6.24 5.22 0.67 variance 38.96 27.24 0.45 Vaccinated pigs (aqueous solvent) 25.20 27.50 1.30 33.00 32.00 - 0.43 31.50 36.00 2.04 35.00 27.00 - 3.27 42.50 42.50 0.00 average 33.44 33.00 - 0.07 and 5.59 5.77 1.83 variance 31.27 33.30 3.34 ΔG7 = 2.67 Terms Weight at D.33 Weight at D.40 Death to: GMQR%: J. 33 and 40 Test Test Witnesses 24.80 20.00 J.6 - 3.23 42.50 35.00 J.6 - 2.94 29.00 25.50 - 1.72 36.00 27.00 J.7 - 3.57 37.00 32.00 J.6 - 2.25 average 33.86 27.90 - 2.74 and 6.24 5.22 0.67 variance 38.96 27.24 0.45 Vaccinated pigs (oily solvent) 33.00 35.00 0.87 35.70 35.50 - 0.08 38.00 36.50 - 0.56 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 ΔG7 = 2.92 Terms Weight at Death to: GMQR% J. 21 and J.28 J.21 J.28 Test Test Witnesses 26.50 20.50 J.5 - 4.53 51.00 47.00 - 1.12 32.00 27.00 - 2.23 31.00 30.00 - 0.46 42.50 39.00 - 1.18 average 36.60 32.70 - 1.90 and 8.91 9.30 1.43 variance 79.34 86.56 2.04 Vaccinated pigs 32.00 31.00 - 0.45 30.00 31.00 0.48 34.00 31.00 - 1.26 27.00 28.50 0.79 29.50 32.00 1.21 average 30.50 30.70 0.15 and 2.37 1.17 0.89 variance 5.60 1.36 0.80 ΔG7 = 2.06 Antibody 14 days after recall Weight of pigs after testing H1N1 H3N2 J.0 J.3 Difference J.3 - J.0 J.7 Difference J.7 - J.0 vaccinated pigs 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 2.10 3 35.50 35.50 0.00 41.40 2.90 1.20 1.8 unproven 2.10 2.7 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 control pigs 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 0.9 1.20 34.50 35.80 1.30 35.40 0.90 0.9 1.20 unproven 0.9 1.20 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 Antibody Swine Flu Antibody Aujeszky H1N1 H3N2 Vaccinated pigs 1.7 1.20 2.10 1.7 2.40 2.40 1.7 2.10 2.10 1.9 1.50 2.10 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 and 0.29 0.38 0.15 Control pigs 0.5 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 0.2 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 and 0.12 / /

Claims (10)

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 corresponding concentration. 2. Installation according to claim 1, characterized in that it is arranged to ensure an intradermal injection of the dose. 3. Installation according to one of claims 1 and 2, characterized in that the supply of vaccine composition is provided by the original bottle disposed in the vicinity of the ejection head. 4. Vaccine composition intended to be administered using the installation according to any one of claims 1 to 3, characterized in that they are live attenuated vaccines. 5. Vaccine composition intended to be administered using the installation according to any one of claims 1 to 3, characterized in that they are inactivated vaccines. 6. Vaccine composition according to claim 4 or 5, characterized in that it is a vaccine against Aujeszky's disease. 7. Vaccine composition according to claim 6 characterized in that the vaccine against Aujeszky's disease is composed of viral subunits. 8. Vaccine composition according to claim 6 or 7 characterized in that the vaccine does not comprise the GI glycoprotein. 9. A vaccine composition according to claim 5 characterized in that it is a vaccine against swine flu. 10. Vaccine composition intended to be administered using the installation according to one any one of claims 1 to 3 characterized in that it comprises an inactivated vaccine against swine flu by oily adjuvant and a live attenuated vaccine against Aujeszky's disease, the adjuvant of the inactivated vaccine serving as solvent for the live attenuated vaccine.