Swine fever. Immunisation of piglets

Comp. lmmun. Microbiol. infect. Dis. Vol. 6, No. 4, pp. 281 289, 1983 Printed in Great Britain. All rights reserved

0147-9571/83 $3.00+0.00 Copyright © 1983 Pergamon Press Ltd

SWINE FEVER IMMUNISATION

OF PIGLETS

P. PRECAUSTA, F. KATO a n d A. BRUN Rhone Merieux, IFFA Laboratory, 254, rue Marcel M&ieux, 69007 Lyon, France (Received 22 March 1983)

Abstract--Vaccination against Swine Fever using the CL Chinese strain can be done in 7-day-old piglets if they are born of non-immune sows. The simultaneous weaning and vaccination emphasises the safety of this strain. The excellent immunity observed confirms the immunocompetence of 7-day-old piglets. In piglets born of immune sows and also weaned at 7 days, passive protection can extend beyond the age of 2 months if the sow is vaccinated several months prior to gestation. The immune level of the piglets would seem to depend on the interval between vaccination of the sow and farrowing and can be attributed to the quality of the antibodies transmitted by the colostrum. Piglets born of sows vaccinated 10 months prior to farrowing can be vaccinated as early as 5 weeks; the protection percentage observed at the age of about 6 months is over 80~. A booster injection at this age then confers immunity to future breeders throughout their economic life, i.e. 4 years in the reported experiment. Key" words: Swine Fever, CL Chinese strain, immunisation, sows, piglets, immunity persistence

IMMUNISATION

DU

PORCELET CONTRE CLASSIQUE

LA

PESTE

PORCINE

Rrsum~-La vaccination contre la peste porcine classique fi~l'aide de la souche chinoise CL peut intervenir ~i l'$ge de 7 jours chez le porcelet issu de truie non immune. La simultanrit6 du sevrage et de la vaccination souligne l'innocuit+ de cette souche. L'excellente immunit6 observ& confirme l'immunocomp&ence du porcelet de 7 jours. Chez les porcelets issus de truie immune, et sevr& 6galement fi 7 jours, la protection passive peut s'&endre au-delfi de l'fige de 2 mois si la truie est vaccin~e plusieurs mois avant la gestation. Le niveau d'immunit+ des porcelets parait en relation avec le drlai vaccination/mise bas de la truie et est attribu6 ~ la qualit6 des anticorps transmis par le colostrum. Des porcelets issus de truies vaccinres 10 mois avant mise bas peuvent &re vaccinrs d~s l'~.ge de 5 semaines; le pourcentage de protection observre ft. l'~.ge de 6 mois environ est sup&ieur ~ 80~. Un rappel effectu6 ~ cet fi.geconfrre alors aux futurs reproducteurs une immunit6 pour la dur~e de leur vie ~conomique, soit 4 ans dans le cadre de l'observation rapport~e. Mots-clffs: Peste Porcine Classique, souche chinoise CL, immunisation, truies, porcelets, durre d'immunit6

1. I N T R O D U C T I O N V a c c i n a t i o n a g a i n s t S w i n e F e v e r is g e n e r a l l y d o n e u s i n g a t t e n u a t e d living v i r u s vaccines. T h e e x c e l l e n t a c t i v i t y o f s u c h v a c c i n e s u n d o u b t e d l y assures p r o t e c t i o n w h e n a n i m a l s w h i c h h a v e n e v e r b e e n v a c c i n a t e d a g a i n s t S w i n e F e v e r are i n v o l v e d , b u t as efficient c o n t r o l o f the disease in h i g h l y c o n t a m i n a t e d r e g i o n s d e p e n d s o n r e g u l a r a n d w i d e s p r e a d v a c c i n a t i o n , piglets b o r n o f v a c c i n a t e d s o w s c a n benefit f r o m a n t i b o d i e s o f c o l o s t r a l origin. V e r y y o u n g piglets are i m m u n o c o m p e t e n t [3, 11, 17, 23] b u t , as e v e r w i t h i m m u n i s a t i o n , t h e p r e s e n c e o f specific a n t i b o d i e s c a n h i n d e r the d e v e l o p m e n t o f a c t i v e i m m u n i t y [1, 4, 6, 7, 13, 20, 22, 24, 25, 27]. M o s t a u t h o r s r e s p e c t a 2 - m o n t h i n t e r v a l b e t w e e n b i r t h a n d v a c c i n a t i o n to p r e v e n t s u c h i n t e r f e r e n c e [5, 8, 12, 18,26]; o t h e r s v a c c i n a t e i m m e d i a t e l y 281

282

P. PRECAUSTAet al.

prior to colostrum intake [14]. Studies were done on piglets to monitor the development and evolution of immunity after vaccination with a CL Chinese strain vaccine. 2. MATERIALS AND METHODS

2.1. Vaccine The obtention and properties of the CL Chinese strain have been the object of prior studies [10, 20, 21]. 2.2. Animals Pigs used during the experiments were either Large White or Landrace/Large White crossbreds from normal, healthy farms free of Swine Fever. This study involved 15 sows and their litters which had never previously been vaccinated against Swine Fever.

2.3. Experimental programme 2.3.1. Vaccination The sows were vaccinated in the following way: group 1:--5 sows, 6 months prior to gestation (i.e. 10 months prior to farrowing); group 2:--3 sows, 1 month prior to gestation (i.e. 5 months prior to farrowing); group 3:--5 sows, during the 2nd or 3rd month of gestation (i.e. 2 to 1 months prior to farrowing); group 4:--2 sows, not vaccinated at all. Piglets born of these sows were weaned at 1 week. Amongst those born of the non-immunised sows, 5 were vaccinated at the age of 1 week and 4 at the age of 9 weeks. The piglets born of immunised sows were divided into different groups as follows. One non-vaccinated group (25piglets). The evolution of antibodies of colostral origin was monitored. The piglets were inoculated with a pathogenic strain at varying intervals after birth. Three vaccinated groups (total of 73piglets). Vaccinated respectively at the age of 1 week, 5-7 weeks and 9 weeks. The evolution of antibodies was monitored as of birth. At the end of the economic life period (22-25 weeks), 66 of the piglets were challenged with a pathogenic strain and the others given a booster injection; antibody evolution was monitored until these piglets were 48 months old. A pathogenic strain challenge was done on these animals at 39 and 48 months. 2.3.2. Immunity testing Immunity was tested by: neutralising serum antibody titration (described elsewhere [19] and titres were expressed in log~0 and challenge with 105LD 100 of pathogenic virus [19]. Challenges done at the end of the economic life period particularly involved fattening animals, aged between 5 and 6 months.

3. RESULTS

3.1. Piglets born of non-immune sows (group 4) Results (Fig. 1) demonstrate that there is no difference between the two groups of piglets (vaccinated at 1 or 9 weeks) regarding antibody evolution (difference 0.1 lOgl0 not significant Fl~ = 1.7, 5 ~ threshold = 4.32), and protection.

Swine fever

283

2.5

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o

~ o

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.o

i

/ / / I

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~ ±Istandarderror

i i I

05

i

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-

'

V I I

I

I I

0

3

6

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V J I I I 9

I 14 Age (weeks)

I

II 12

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18

I

22 23

Fig. 1. E v o l u t i o n o f a n t i b o d i e s as a function o f age in piglets b o r n o f n o n - i m m u n e sows. C = control; V = v a c c i n a t i o n ; n u m b e r s in circles = h e a l t h y / c h a l l e n g e d . ( - - ) Piglets v a c c i n a t e d at 1 week; ( - - - ) piglets v a c c i n a t e d at 9 weeks.

3.2. Piglets born of immune sows (groups 1-3) 3.2.1. Results can be found in Tables 1 and 2 and are summarised in Fig. 2 It is to be noted that the evolution of colostral antibodies in the piglets of the different groups differs significantly (F~6--1.84, 5~o threshold = 4.23), especially the antibodies observed in piglets born of sows vaccinated 6 months before gestation (group 1). In these piglets protection is complete at the age of 7 weeks and high at 10 weeks.

3.2.2. Immunisation of piglets Piglets born of sows vaccinated during gestation (group 3, Fig. 3). Piglets vaccinated at the age of 9 weeks present mean antibody titres slightly superior (difference 0.3 log,0 significant: F~0 = 6.1, 5~o threshold = 4.17) to those vaccinated at the age of 1 week. During the economic life of the animals, antibodies remained at a low rate. At the end of the economic life period, the group vaccinated at 9 weeks was the only group where a / / t h e animals were protected. Table 1. Evolution of passive antibodies in piglets born of sows vaccinated before and during gestation Vaccination of sows No. of litters Maternal serum antibody titre Antibody titre in piglets aged: 1 week 2-3 weeks 4 weeks 5 weeks 6-7 weeks 9 weeks Challenge Age of piglets (weeks) Healthy/challenged

One month before gestation

Third month of gestation

Second month of gestation

1

2

3

4

5

6

7

8

2.51

2.58

2.50

2.0(,

2.49

2.0

2.3

2.4

1.92 1.23 0.60 0.72 0.43 0.60

2.19 1.30 0.85 0.68 0.66 0.60

2.16 1.36 1.0 0.32 0.77 0.56

-1.43 0.84 . 0.30 --

1.09 1.01 .

1.24 --

1.79 0.60 .

1.18 0.96

.

. 0.60 --

2-3

4

6-7

2/3

3/3

2/3

.

.

. 0.60

0.30

0.42 --

0/1

0/1

22-25

Not challenged 0/1

0/1

284

P.

et al.

PRECAUSTA

Table 2. Evolution of passive antibodies in piglets born of sows vaccinated 6 months before gestation No. of litters

g

10

11

12

13

Maternal serum antibody titres

3.09

2.65

2.03

2.34

2.82

1.89 2.0 1.48

1.97 1.85 1.46

3.24 1.64 1.33

1/1 0/1"*

1/1 1/1

UI 0/1.*

Antibody titre in piglets aged

~ I

Protection

5 weeks 6/7 weeks 10 weeks

2.04 2.10 1.68

7 weeks 10 weeks

1/1" 1/1

2.50 2.08 1.35

2.93 1.91 1.16 2/2 2/2

* Healthy/challenged. **Survived, but lesions found at autopsy.

Piglets born of sows vaccinated 1 month before gestation (group 2, Fig. 4). Piglets were vaccinated at the age of 5, 7 or 9 weeks. Despite the fact that they had equivalent titres at the moment of vaccination, the antibody response was found to be in relation to the date of vaccination, i.e. the later the vaccination date, the higher the antibody response (F~0=61.1, 5% threshold=4.17). At the end of the economic life period, the group vaccinated at the age of 2 months was the only group to be entirely protected; these results confirm preceding results. Piglets born of sows vaccinated 6 months before gestation (group 1, Fig. 5). Piglets were vaccinated at the age of 5 weeks. It should be pointed out that despite their very young age and their high antibody titre at the time of vaccination, protection at the end of the economic life period remained strong ( # 82%). So when sows are vaccinated several months prior to gestation, piglets are able to benefit from the following: passive protection lasting for more than 2 months in certain animals (Fig. 2); good post-vaccination inmunity level at 5 weeks (Fig. 5). The level of protection at the end of the economic life period doses not seem to be directly linked with the antibody titre; it is highly likely that another factor has a role to play: nature of antibodies or cell mediation immunity? recently vaccinated • formerly vaccinated A

T i t r e s in sows

and and

their piglets • their piglets •

-

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E I -,1o

I

I

2/3

I

I

4

I

I

I

6/7

Age of piglets

I

I

I

i0 ( weeks )

Fig. 2. E v o l u t i o n o f passive a n t i b o d i e s in piglets b o r n o f i m m u n e sows. N u m b e r s in circles = healthy/challenged.

Swine fever

285

25 20

T.

I 5

I0 05

,!,

, !,,,

0 I 2

6

9

111213

1

,L,

18

2 2 25

Fig. 3. Evolution of antibodies in piglets born of sows vaccinated at 2nd and 3rd m o n t h of gestation. N u m b e r s in circles = healthy/challenged. ( ) Piglets vaccinated at 1 week; (---) piglets vaccinated at 9 weeks.

~o

~,

..• ................. {

25

(~

.: 20

•" ~

x:l

E

05 I 5

I i 7 9

I 16

i i 2627 •

_+ S t a n d a r d error

Fig. 4. Evolution of antibodies in piglets born of sows vaccinated one m o n t h before gestation. N u m b e r s in circles = healthy/challenged. ( ) Piglets vaccinated at 5 weeks; (---) 7 weeks; ( . . . . . ) 9 weeks.

25

_

1

20 15 P.O

0.5 I

I

0

5

,

Age

I

1

I0

i5

I ~ I I I 2022252627

(weeks)

Fig. 5. Evolution of antibodies in piglets born of sows vaccinated 6 m o n t h s before gestation. N u m b e r s in circles = healthy/challenged; arrow = vaccination. C I.M.I D. 6/4~B

286

P. PRECAUSTA et al.

3.2.3. Immunity persistence It appeared to be interesting to check the effect of a booster injection in primovaccinated piglets born of sows which themselves had been vaccinated 6 months prior to gestation (group 1). Figure 6 illustrates the evolution of the antibodies and protection up to the age of 4 years, i.e. 42 months post-booster. Protection was found to be excellent. 4. DISCUSSION All the groups of piglets were weaned at 7 days meaning that they could benefit from the specific or non-specific gamma-globulins depending on whether they were born of immune or non-immune sows [23]. Certain piglets were vaccinated as soon as they had been weaned. The absence of a reaction even in the piglets who had not had colostral antibodies emphasises the safety of the CL strain. It can also be said that this interval avoids the period of immunodepression attributed to the rise in the blood corticoids at birth [15-23]. Table 3 summarises the results presented. Very young piglets are immunocompetent [11-15] and can be vaccinated as of the 7th day so long as specific colostral antibodies have not been received; the safety of the CL Chinese strain allows early intervention. For vaccinated sows with an equivalent antibody titre on farrowing (FI1 = 1.6, 5~ threshold = 4.84) protection at the end of the economic life period of the vaccinated piglets is function of the "vaccination/farrowing" interval in sows, more so than the antibody titre in piglets at vaccination. This concords with analogous observations reported by other authors [2, 8, 9, 16] and attributes this different behaviour to a difference in the nature of the antibodies transmitted by the colostrum. These authors interpret the results as follows: the former immunisation antibodies (dominantly IgG) would appear to be more avid but less inhibitive, with the

T

I E ,< I

I

I

I

I

I

I

I

6

f2

r8

24

30

36

39

48

Age of animals (months)

Fig. 6. E v o l u t i o n o f a n t i b o d i e s a n d p r o t e c t i o n over the 4-year o b s e r v a t i o n period. A r r o w = v a c c i n a t i o n or booster; n u m b e r s in circles = h e a l t h y / c h a l l e n g e d .

Swine fever

287

Table 3. Immune response of piglets as a function of the vaccination/farrowing interval Sows Interval vaccination/ farrowing (weeks) Not vaccinated 4

Piglets Age at vaccination (weeks) Antibodies farrowing 0 2.35

1 0* 1.6"* 4/4***

(lOO%)

5/7

9

--

0-1.8 5/5

1.39 0.35 4/8

(50%)

21

2.53

--

42

2.56

--

(lOO%) 0.60-0.79 9/9

(1oo%)

0.60-1.22 8/12 (66%) 2.43 1.23 18/22

(82%)

0.60-2.55 6/6 (100~) --

* M e a n a n t i b o d y titre at vaccination. * * M e a n a n t i b o d y titre at challenge. ***Protected/challenged at the end o f the e c o n o m i c life period.

opposite being the case for recent immunisation antibodies which would be highly inhibitive antibodies, strongly neutralising the vaccine virus, reducing immune response in the same way. These two notions, founded on the analysis of passive and active antibody titres, bring a certain explanation as to the different immune response of piglets which are carriers of equivalent titre colostral origin antibodies. The comparison of Tables 1-3 demonstrates a certain number of paradoxical elements: Non-vaccinated piglets born of immune sows are protected (6/6 and 2/3) against a challenge done at 7 weeks. Piglets born of immune sows and vaccinated at the age of 5-7 weeks develop a state of immunity expressed by the protection rate (66 and 82~o) observed during a challenge done at the end of the economic life period, implying that the antibodies of colostral origin would be capable of neutralising the pathogenic virus, although allowing the development of immunity engendered by the attenuated living virus of the vaccine. A similar observation has already been described [13] and explained by the notion of antibody threshold levels: antibody threshold until passive protection is observed: results reported here enable this threshold to be situated after 7 weeks for piglets born of sows, vaccinated 10 months prior to farrowing; antibody threshold from which active immunisation is possible: the high protection observed ( # 80~) enables this threshold to be situated at the age of 5 weeks for these same piglets. The overlapping of these two thresholds determines a zone corresponding to a period in the life of the piglets permitting both passive protection and active immunisation of the piglet. The size of this zone depends, for each individual piglet, on the level and quality of the antibodies transmitted by the sow. When considered in the light of the experiment, the development of active immunity is function of the reciprocal of the level of antibodies of colostral origin at the time of vaccination of the piglet [13]: high level: n o active immunisation; lower level: more or less intense active immunisation with development (or not) of antibodies. In this last case, there would be primosensitization of the immunitary system. The challenge (in this case acting as a booster) triggers off an antibody response of the secondary type which confirms the primosensitization caused by the former vaccination. Throughout the reported observations, the absence of serum sampling either in the week following the challenges or the booster vaccination at 22 weeks mean that this

288

P. PRECAUSTAet al.

p r i m o s e n s i t i z a t i o n c o u l d n o t be d e m o n s t r a t e d . N e v e r t h e l e s s the results o f p r o t e c t i o n o b s e r v e d in the d i f f e r e n t g r o u p s o f piglets tie u p w i t h the n o t i o n o f t h r e s h o l d s a n d w i t h the e x p l i c a t o r y i m m u n i t a r y m e c h a n i s m s . T h e p r o g r e s s i v e d i s a p p e a r a n c e o f a n t i b o d i e s o f c o l o s t r a l o r i g i n m e a n s the i n s t a l l a t i o n o f i m m u n i t y d e m o n s t r a t e d by a h i g h p e r c e n t a g e o f p r o t e c t i o n (82~o) a g a i n s t a severe l a b o r a t o r y c h a l l e n g e f o r v a c c i n a t i o n d o n e at 5 w e e k s in piglets b o r n o f sows v a c c i n a t e d 10 m o n t h s p r i o r to f a r r o w i n g . T h e s e results i n d i c a t e t h a t p r o p h y l a x i s a g a i n s t S w i n e F e v e r c a n be e n v i s a g e d for a w h o l e h e r d a n d o v e r time. I n i m m u n o l o g i c a l l y " n e w " herds: piglets c a n be v a c c i n a t e d as o f the 7th day. I n a f o r m e r l y v a c c i n a t e d h e r d , piglets can be v a c c i n a t e d as o f the e n d o f the 1st m o n t h whilst t h e y are still p r o t e c t e d by the a n t i b o d i e s o f c o l o s t r a l origin; this v a c c i n a t i o n c o v e r s p r o t e c t i o n o f m o r e t h a n 80~o o f the a n i m a l s c h a l l e n g e d u n d e r l a b o r a t o r y c o n d i t i o n s . A b o o s t e r g i v e n to f u t u r e b r e e d e r s t o w a r d s the 5th m o n t h c o n f e r s e x c e l l e n t p r o t e c t i o n t h r o u g h o u t their e c o n o m i c life. Acknowledgement--The authors would like to express their thanks to G. Tixier for his help in the analysis of

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18. Olah, P., Immunisation of suckling pigs against swine fever using vaccine, Magy. Allat. Lapja Budapest 7, 371 (1969). 19. Pr+causta, P. et Perrenot, F., Titrage des anticorps neutralisants antipeste porcine classique par la m&hode d'immunofluorescence, Rec. MOd. V&. Alfort 149, 1567 1576 (1973). 20. Pr+causta, P., Brun, A., Kato, F., Terr6, J. et Marcon, Ch., Etude d'un vaccin pr6par6 fi partie de la souche chinoise CL adapt6e fi la culture cellulaire, Rev. Mbd. V&. 126, 969-981 (1975). 21. Pr6causta, P., Kato, F. et Brun, A., Peste porcine classique immunisation active conf6r6e par la souche chinoise CL aux porcelets issus de truies indemnes, XVth Intern. Congress Standard&. and Use of Vaccine in the Develop. Countries. Le Gosier, La Guadeloupe, April 16-20 (1978). 22. Rouze, P., Houdayer, M. et Metzger, J. J., La r6ponse immunitaire du porcelet: effets de l'immunit+ passive sur l'immunisation du porcelet induite fi l'aide d'un antig6ne inerte: le lysozyme, J. Rech. Porc., France 363-370 (1975). 23. Rouze, P., Competence immunitaire du porcelet avant et apr6s la naissance, Rec. M~d. V&. 152, 157-162 (1976). 24. Sasahara, J., Kumagai, T., Shimizu, Y. and Furuuchi, S., Field experiments of Hog Cholera live vaccine prepared in guinea-pig kidney cell culture, Natn. Inst. Am. Hlth Quart. 9, 83-91 (1969). 25. Terpstra, C. and Tielen, M. J. M., Antibody response against swine fever following vaccination with C-Strain virus--Hog Cholera/Classical Swine Fever and African Swine Fever; Commission of the European Communities EUR 5904 EN, 364-378 (1977). 26. Terpstra, C. and Tielen, M. J. M., Antibody response against swine fever following vaccination with C strain virus, Zblt. vet. Med. B23, 809-821 (1976). 27. Tesmer, S., Urbaneck, D., Kaden, V., Wittmann, W. et Hannefeld, Contribution fi l'6tude du vaccin ~ virus vivant contre la peste porcine, produit ~i partir de la souche vaccinale C chez des truies gestantes et leur prog~niture, Monatsh. Vet. 7, 251-254 (1973).