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Response of pups with maternal derived antibody to modified-live canine parvovirus vaccine
Comp. Immun. Microbiol. infect. Dis. Vol. 15, No. 4, pp. 281-283, 1992 Printed in Great Britain. All fights reserved
0147-9571/92 $5.00 + 0.00 Copyright © 1992 Pergamon Press Ltd
RESPONSE OF PUPS WITH MATERNAL DERIVED ANTIBODY TO MODIFIED-LIVE CANINE PARVOVIRUS
VACCINE
C . BUONAVOGLIA, t* M. TOLLIS, 2 D. BUONAVOGLIA I and A. PUCCINI ~ t Istituo di Malattie infettive e parassitarie degli animali domestici, Facoltli di Medicina Veterinaria, UniversitY. degli Studi di Bari and 2Istituto Superiore di Sanitli, Laboratorio di Medicina Veterinaria, Roma, Italy Al~traet--The AA reports the results of vaccination against canine parvovirus (CPV) of pups with maternal antibody, utilizing a modified-live virus (MLV) CPV vaccine having a titer of 107 TCIDs0/dose. This vaccine was shown to be effective also when HI antibody titers of pups were ~< 1:80.
Key words: Canine parvovirus, vaccination, maternal, antibody, pup. R6smn6----R(~ponse de chiots avec les anticorps d'origine maternelle fi le vaccin :i virus vivant modifi(~e de la parvovirose du chien. Les AA rapportent les r6sultats de la vaccination des chiots avec les anticorps d'origine maternelle avec un vaccin fi virus vivant modifi6e de la parvovirose du chien. Le titre de la souche vaccinale sur cultures cellulaires est l07 TCIDs0/dose. Ce vaccin donne aussi de bons r6sultats en presence de titres d'anticorps HI des chiots ~<1:80.
Mots clefs: Parvovirus, chien, vaccination, anticorps maternelles.
INTRODUCTION
Modified live virus (MLV) vaccines are preferably used for the prophylaxis of canine parvovirus (CPV) infection in dogs [1-7]. Nevertheless even good quality vaccines, sometimes fail to elicit an adequate immune response in dogs. The most important factor of this failure is the presence of maternal antibody in pups [4, 8]. These antibody can interfere with vaccine virus, thus preventing the onset of a valid immunity. In a previous study [4], we have reported that an HI titer of maternal antibody higher than ! : 20 is capable to neutralize MLV-CPV vaccine and prevent the establishment of protective immunity. The vaccine had a titer of 105 median tissue culture infectious doses (TCID~0). It has been stated that, since pups with HI titer < 1: 80 are susceptible to CPV infection, there is an "immunity gap" which can last several weeks; during this period these animals cannot be actively immunized because of the presence of maternal antibody, but are nevertheless susceptible to infection. This event is particularly serious in infected kennels. This study reports results of vaccination of pups with maternal antibody to CPV, utilizing a MLV-CPV vaccine with a titer "per dose" higher than the one utilized in a previous experiment [4]. *Author for correspondence. 281
282
C. BUONAVOGLIA et at.
MATERIALS AND METHODS
Vaccine Pups were vaccinated with MLV-CPV vaccine [2] having a titer of (1 dose).
10 7 TCIDs0/per
I ml
Animals 72 pups delivered by 17 mothers having HI antibody titers against CPV > I : 2560 have been used. Experimental protocol At the moment of delivery, blood samples were drawn from the mothers for HI antibody determination to CPV. Blood collection and vaccination of all pups was firstly carried out at 4 weeks of age and subsequently every 2 weeks until the 12th week of age. Antibody determination HI antibody against CPV was determined by HI test performed at + 4 C , using pig erythrocytes and 8 U H A of CPV. RESULTS
Response of dogs to CPV vaccination As shown in Table 1, at 4 weeks of age the HI titer was respectively I: 160 in 5 pups, 1:320 in 52 pups and 1:640 in 15 pups. At 6 weeks of age, following the first vaccination, no seroconversion was noted in any subject and HI titers ranged between !:40 and 1:320. Following the second vaccination the antibody determination at 8 weeks of age revealed a good immune response in 18 pups (8 pups showed HI titers of 1:1280, 10 pups />1:2560). At 10 weeks of age 64 out of the 72 dogs showed a specific immune response with HI titers peaking 1:1280 in 7 dogs and >_,1:2560 in 57 dogs. At 12 weeks of age all dogs resulted actively immunized. Relationship between titer of maternally derived antibody and response to CPV vaccination In Table 2 the titers of maternally derived HI antibody are grouped in two ranges: !:40-1:80 (A) and 1:160-1:640 (B). Furthermore, in parentheses is reported the number Table I. Response after CPV vaccination of 72 dogs with maternal antibody HI antibody*
4
6
Age¢ 8
IO
20 40 2 15 8 80 2L 32 160 5++ 40 7 320 52 9 640 15 1280 8 7 />2560 10 57 *Hemagglutination inhibition test. rAge of dogs (weeks) at the time of ~accination. ++Number of dogs corresponding to HI titer.
12
Table 2. Relationship between titer of maternally derived antibody and response to CPV vaccination Age'f Range of ................... HI titers* 4 6 8 10 40 80 (A) 160 640 (B)
4 68
0~ 72
23 (18)~ 49 (0)
47 (46) 7 (0)
8 (8) 0
*Hemagglutination inhibition test. rAge of dogs (weeks). 1:Number of dogs corresponding to HI titer. §Number of dogs with serological response to CPV. 2 weeks later.
Response of pups with maternal derived antibody
283
o f p u p s that s h o w e d an active i m m u n e response 2 weeks after the vaccination. A t 6 weeks o f age, 23 p u p s have H I a n t i b o d y titers included in the range A, a n d 49 in the range B. T h e H I a n t i b o d y titers e v a l u a t e d after 2 weeks showed an active i m m u n e response in 18 o f the 23 p u p s included in the r a n g e A. N o n e o f the 49 p u p s o f the range B showed an active i m m u n e response. T h e HI a n t i b o d y d e t e r m i n a t i o n , carried o u t 2 weeks after the v a c c i n a t i o n m a d e at 8 weeks o f age, s h o w e d an active i m m u n e response in 46 o f the 47 p u p s included in the range A. A t 10 weeks o f age, 8 p u p s still showed H I a n t i b o d y titers o f 1:40. 2 weeks after the v a c c i n a t i o n these a n i m a l s t o o showed on active i m m u n e response. DISCUSSION T h e results o b t a i n e d in the present s t u d y allow i m p o r t a n t c o n s i d e r a t i o n s r e g a r d i n g vaccine p r o p h y l a x i s a g a i n s t C P V infection in p u p s with m a t e r n a l a n t i b o d y . It must be e m p h a s i z e d that a vaccine d o s e c o r r e s p o n d i n g to 107 TCID/s0 is safe for pups. P r e l i m i n a r y tests on s e r o n e g a t i v e p u p s v a c c i n a t e d with two doses o f the s a m e vaccine utilized in the present study, p r o v i d e d g o o d i n d i c a t i o n s o f its i n n o c u i t y for the a n i m a l s ( d a t a not published). In a p r e v i o u s e x p e r i m e n t a vaccine dose c o r r e s p o n d i n g to 105 T C I D / ~ elicited serological response to C P V in p u p s with m a t e r n a l a n t i b o d y o n l y when v a c c i n a t i o n was m a d e at 1 1-I 3 weeks o f age [4]. In the present s t u d y v a c c i n a t i o n at 6 a n d 8 weeks induced an i m m u n e response respectively in 18 a n d 46 p u p s which definitely c o r r e s p o n d s to s e r o c o n v e r s i o n in 89% o f v a c c i n a t e d animals. These d a t a confirm the results r e p o r t e d by Van A a r l e a n d G e a r y [9]. C o n s i d e r i n g the a n t i b o d y titers o f p u p s at the time o f vaccination, the vaccine was shown to be effective also when H I titers were ~< 1 : 80. In conclusion there are g o o d indications that the interference o f m a t e r n a l a n t i b o d y with C P V vaccines could be c i r c u m v e n t e d by using a M L V - C P V vaccine h a v i n g a high titer. REFERENCES l, Bass E. P., Gill M. A. and Beckenhauer W. H. Development of a modified live canine origin parvovirus vaccine. J. Am. Vet. reed. Assoc. 181, 909-913 (1982). 2. Buonavoglia C., Compagnucci M. and Orfei Z. Dog response to plaque variant of canine parvovirus. Zbl. reed. Vet. 30, 526 (1983). 3. Buonavoglia C., Gravino E. and Orfei Z. Profilassi vaccinale della parvovirosi del cane: risultati sperimentali sull'impiego di vaccini omologhi a virus inanivato e attenuato. Riv. Zootec. Vet. 12, 305-309 (1984). 4. Buonavoglia C., De Nardo P., Reitano M. and Orfei Z. Persistenza nei cuccioli degli anticopri di derivazione materna nei confronti del parvovirus del cane e Ioro interferenza nella risposta sierologia alia vaccinazione. Clin. Veterin. 108, 19-23 (1985). 5. Carmichael L. E., Joubert J. C. and Pollock R. V. H. A modified live canine parvovirus vaccine- -I!. Immune response. Cornell Vet. 73, 13 (1983). 6. Churchill A. E. Preliminary development of a live attenuated canine parvovirus vaccine from an isolate of British origin. Vet. Rec. 120, 334-339 (1987). 7. O'Brien S. E.0 Roth J. A. and Hill B. L. Response of pups to modified-live canine parvovirus component in a combination vaccine. J A V M A 188, 699-701 (1986). 8. Pollock R. V. H. and Carmichael L. E. Maternally derived immunity to canine parvovirus infection: transfer, decline, and interference with vaccination. J. Am. Vt. reed. Assoc. 180, 37-42 (1982). 9. Van Aarle P. A. M. and Geary M. R. Up to date on new canine parvo-vaccine. Tijdschr. Diergen. I l I, 15S-16S (1986).
0147-9571/92 $5.00 + 0.00 Copyright © 1992 Pergamon Press Ltd
RESPONSE OF PUPS WITH MATERNAL DERIVED ANTIBODY TO MODIFIED-LIVE CANINE PARVOVIRUS
VACCINE
C . BUONAVOGLIA, t* M. TOLLIS, 2 D. BUONAVOGLIA I and A. PUCCINI ~ t Istituo di Malattie infettive e parassitarie degli animali domestici, Facoltli di Medicina Veterinaria, UniversitY. degli Studi di Bari and 2Istituto Superiore di Sanitli, Laboratorio di Medicina Veterinaria, Roma, Italy Al~traet--The AA reports the results of vaccination against canine parvovirus (CPV) of pups with maternal antibody, utilizing a modified-live virus (MLV) CPV vaccine having a titer of 107 TCIDs0/dose. This vaccine was shown to be effective also when HI antibody titers of pups were ~< 1:80.
Key words: Canine parvovirus, vaccination, maternal, antibody, pup. R6smn6----R(~ponse de chiots avec les anticorps d'origine maternelle fi le vaccin :i virus vivant modifi(~e de la parvovirose du chien. Les AA rapportent les r6sultats de la vaccination des chiots avec les anticorps d'origine maternelle avec un vaccin fi virus vivant modifi6e de la parvovirose du chien. Le titre de la souche vaccinale sur cultures cellulaires est l07 TCIDs0/dose. Ce vaccin donne aussi de bons r6sultats en presence de titres d'anticorps HI des chiots ~<1:80.
Mots clefs: Parvovirus, chien, vaccination, anticorps maternelles.
INTRODUCTION
Modified live virus (MLV) vaccines are preferably used for the prophylaxis of canine parvovirus (CPV) infection in dogs [1-7]. Nevertheless even good quality vaccines, sometimes fail to elicit an adequate immune response in dogs. The most important factor of this failure is the presence of maternal antibody in pups [4, 8]. These antibody can interfere with vaccine virus, thus preventing the onset of a valid immunity. In a previous study [4], we have reported that an HI titer of maternal antibody higher than ! : 20 is capable to neutralize MLV-CPV vaccine and prevent the establishment of protective immunity. The vaccine had a titer of 105 median tissue culture infectious doses (TCID~0). It has been stated that, since pups with HI titer < 1: 80 are susceptible to CPV infection, there is an "immunity gap" which can last several weeks; during this period these animals cannot be actively immunized because of the presence of maternal antibody, but are nevertheless susceptible to infection. This event is particularly serious in infected kennels. This study reports results of vaccination of pups with maternal antibody to CPV, utilizing a MLV-CPV vaccine with a titer "per dose" higher than the one utilized in a previous experiment [4]. *Author for correspondence. 281
282
C. BUONAVOGLIA et at.
MATERIALS AND METHODS
Vaccine Pups were vaccinated with MLV-CPV vaccine [2] having a titer of (1 dose).
10 7 TCIDs0/per
I ml
Animals 72 pups delivered by 17 mothers having HI antibody titers against CPV > I : 2560 have been used. Experimental protocol At the moment of delivery, blood samples were drawn from the mothers for HI antibody determination to CPV. Blood collection and vaccination of all pups was firstly carried out at 4 weeks of age and subsequently every 2 weeks until the 12th week of age. Antibody determination HI antibody against CPV was determined by HI test performed at + 4 C , using pig erythrocytes and 8 U H A of CPV. RESULTS
Response of dogs to CPV vaccination As shown in Table 1, at 4 weeks of age the HI titer was respectively I: 160 in 5 pups, 1:320 in 52 pups and 1:640 in 15 pups. At 6 weeks of age, following the first vaccination, no seroconversion was noted in any subject and HI titers ranged between !:40 and 1:320. Following the second vaccination the antibody determination at 8 weeks of age revealed a good immune response in 18 pups (8 pups showed HI titers of 1:1280, 10 pups />1:2560). At 10 weeks of age 64 out of the 72 dogs showed a specific immune response with HI titers peaking 1:1280 in 7 dogs and >_,1:2560 in 57 dogs. At 12 weeks of age all dogs resulted actively immunized. Relationship between titer of maternally derived antibody and response to CPV vaccination In Table 2 the titers of maternally derived HI antibody are grouped in two ranges: !:40-1:80 (A) and 1:160-1:640 (B). Furthermore, in parentheses is reported the number Table I. Response after CPV vaccination of 72 dogs with maternal antibody HI antibody*
4
6
Age¢ 8
IO
20 40 2 15 8 80 2L 32 160 5++ 40 7 320 52 9 640 15 1280 8 7 />2560 10 57 *Hemagglutination inhibition test. rAge of dogs (weeks) at the time of ~accination. ++Number of dogs corresponding to HI titer.
12
Table 2. Relationship between titer of maternally derived antibody and response to CPV vaccination Age'f Range of ................... HI titers* 4 6 8 10 40 80 (A) 160 640 (B)
4 68
0~ 72
23 (18)~ 49 (0)
47 (46) 7 (0)
8 (8) 0
*Hemagglutination inhibition test. rAge of dogs (weeks). 1:Number of dogs corresponding to HI titer. §Number of dogs with serological response to CPV. 2 weeks later.
Response of pups with maternal derived antibody
283
o f p u p s that s h o w e d an active i m m u n e response 2 weeks after the vaccination. A t 6 weeks o f age, 23 p u p s have H I a n t i b o d y titers included in the range A, a n d 49 in the range B. T h e H I a n t i b o d y titers e v a l u a t e d after 2 weeks showed an active i m m u n e response in 18 o f the 23 p u p s included in the r a n g e A. N o n e o f the 49 p u p s o f the range B showed an active i m m u n e response. T h e HI a n t i b o d y d e t e r m i n a t i o n , carried o u t 2 weeks after the v a c c i n a t i o n m a d e at 8 weeks o f age, s h o w e d an active i m m u n e response in 46 o f the 47 p u p s included in the range A. A t 10 weeks o f age, 8 p u p s still showed H I a n t i b o d y titers o f 1:40. 2 weeks after the v a c c i n a t i o n these a n i m a l s t o o showed on active i m m u n e response. DISCUSSION T h e results o b t a i n e d in the present s t u d y allow i m p o r t a n t c o n s i d e r a t i o n s r e g a r d i n g vaccine p r o p h y l a x i s a g a i n s t C P V infection in p u p s with m a t e r n a l a n t i b o d y . It must be e m p h a s i z e d that a vaccine d o s e c o r r e s p o n d i n g to 107 TCID/s0 is safe for pups. P r e l i m i n a r y tests on s e r o n e g a t i v e p u p s v a c c i n a t e d with two doses o f the s a m e vaccine utilized in the present study, p r o v i d e d g o o d i n d i c a t i o n s o f its i n n o c u i t y for the a n i m a l s ( d a t a not published). In a p r e v i o u s e x p e r i m e n t a vaccine dose c o r r e s p o n d i n g to 105 T C I D / ~ elicited serological response to C P V in p u p s with m a t e r n a l a n t i b o d y o n l y when v a c c i n a t i o n was m a d e at 1 1-I 3 weeks o f age [4]. In the present s t u d y v a c c i n a t i o n at 6 a n d 8 weeks induced an i m m u n e response respectively in 18 a n d 46 p u p s which definitely c o r r e s p o n d s to s e r o c o n v e r s i o n in 89% o f v a c c i n a t e d animals. These d a t a confirm the results r e p o r t e d by Van A a r l e a n d G e a r y [9]. C o n s i d e r i n g the a n t i b o d y titers o f p u p s at the time o f vaccination, the vaccine was shown to be effective also when H I titers were ~< 1 : 80. In conclusion there are g o o d indications that the interference o f m a t e r n a l a n t i b o d y with C P V vaccines could be c i r c u m v e n t e d by using a M L V - C P V vaccine h a v i n g a high titer. REFERENCES l, Bass E. P., Gill M. A. and Beckenhauer W. H. Development of a modified live canine origin parvovirus vaccine. J. Am. Vet. reed. Assoc. 181, 909-913 (1982). 2. Buonavoglia C., Compagnucci M. and Orfei Z. Dog response to plaque variant of canine parvovirus. Zbl. reed. Vet. 30, 526 (1983). 3. Buonavoglia C., Gravino E. and Orfei Z. Profilassi vaccinale della parvovirosi del cane: risultati sperimentali sull'impiego di vaccini omologhi a virus inanivato e attenuato. Riv. Zootec. Vet. 12, 305-309 (1984). 4. Buonavoglia C., De Nardo P., Reitano M. and Orfei Z. Persistenza nei cuccioli degli anticopri di derivazione materna nei confronti del parvovirus del cane e Ioro interferenza nella risposta sierologia alia vaccinazione. Clin. Veterin. 108, 19-23 (1985). 5. Carmichael L. E., Joubert J. C. and Pollock R. V. H. A modified live canine parvovirus vaccine- -I!. Immune response. Cornell Vet. 73, 13 (1983). 6. Churchill A. E. Preliminary development of a live attenuated canine parvovirus vaccine from an isolate of British origin. Vet. Rec. 120, 334-339 (1987). 7. O'Brien S. E.0 Roth J. A. and Hill B. L. Response of pups to modified-live canine parvovirus component in a combination vaccine. J A V M A 188, 699-701 (1986). 8. Pollock R. V. H. and Carmichael L. E. Maternally derived immunity to canine parvovirus infection: transfer, decline, and interference with vaccination. J. Am. Vt. reed. Assoc. 180, 37-42 (1982). 9. Van Aarle P. A. M. and Geary M. R. Up to date on new canine parvo-vaccine. Tijdschr. Diergen. I l I, 15S-16S (1986).