Vanguard 5/CV-L (Canada)

Manufacturer: Pfizer

Canine Distemper-adenovirus Type 2-coronavirus-parainfluenza-parvovirus Vaccine

Modified Live and Killed Virus

Leptospira Canicola-icterohaemorrhagiae Bacterin

For use in dogs only

Product Description

Vanguard 5/CV-L is for vaccination of healthy dogs 6 weeks of age or older as an aid in preventing canine distemper caused by canine distemper (CD) virus, infectious canine hepatitis (ICH) caused by canine adenovirus type 1 (CAV-1), respiratory diseases caused by canine adenovirus type 2 (CAV-2), canine parainfluenza caused by canine parainfluenza (CPI) virus infection, disease caused by canine parvovirus (CPV) and canine coronavirus (CCV), and leptospirosis caused by Leptospira canicola and L. icterohaemorrhagiae. Vanguard 5/CV-L is a freeze-dried preparation of attenuated strains of CD virus, CAV-2, CPI virus, CPV, and inactivated whole cultures of L. canicola and L. icterohaemorrhagiae plus a liquid preparation of inactivated CCV with an adjuvant. All viruses were propagated in established cell lines. The CPV fraction was attenuated by low passage in the canine cell line and at that passage level has immunogenic properties capable of overriding maternal antibodies. Some puppies in the field may have higher levels of maternal antibodies than those evaluated in our pivotal efficacy study. The liquid component is used to rehydrate the freeze-dried component, which is packaged with inert gas in place of vacuum.

Disease Description

CD is a universal, high-mortality viral disease with variable manifestations. Approximately 50% of nonvaccinated, nonimmune dogs infected with CD virus develop clinical signs, and approximately 90% of those dogs die.¹ ICH, caused by CAV-1, is a universal, sometimes fatal, viral disease of dogs characterized by hepatic and generalized endothelial lesions. CAV-2 causes respiratory disease which in severe cases may include pneumonia and bronchopneumonia. CPI is a common viral upper respiratory disease. Uncomplicated CPI may be mild or subclinical, with signs becoming more severe if concurrent infection with other respiratory pathogens exists. CPV infection results in enteric disease characterized by sudden onset of vomiting and diarrhea, often hemorrhagic. Leukopenia commonly accompanies clinical signs. Susceptible dogs of any age can be affected, but mortality is greatest in puppies. CCV also causes enteric disease. Characteristics include depression, anorexia, fever, vomiting, and diarrhea. Particularly in puppies, potentially life-threatening dehydration may result from severe diarrhea. Leptospirosis occurs in dogs of all ages, with a wide range of clinical signs and chronic nephritis generally following acute infection. Infection with L. canicola and L. icterohaemorrhagiae cannot be differentiated clinically.

Laboratory procedures are frequently employed to differentiate CPV and CCV infections due to their clinical similarities. Laboratory diagnosis based solely on hemagglutination (HA) tests, however, may not distinguish between the 2 agents because HA tests can yield positive results when either CPV or CCV is present, particularly at low levels of HA activity. The result may be a false positive diagnosis for either virus when in fact the other is the agent of disease. Comprehensive protection thus requires vaccination for both CPV and CCV.

Safety And Efficacy

Vanguard 5/CV-L was subjected to comprehensive safety testing. It was shown safe in laboratory tests and in clinical trials under field conditions. Laboratory evaluation demonstrated that Vanguard 5/CV-L aided in preventing CD, ICH, CAV-2 respiratory disease, CPI, CPV and CCV enteritis, and leptospirosis caused by L. canicola, and L. icterohaemorrhagiae, and that no immunologic interference existed among the vaccine fractions.

It has been demonstrated that CAV-2 vaccine cross-protects against ICH caused by CAV-1. The CAV-2 fraction in Vanguard vaccines is used as a replacement for CAV-1 because it has significant advantages. Some CAV-1 vaccines may produce undesirable reactions, including persistent kidney infections, uveitis, and corneal opacity (“blue eye”), which have not been reported after vaccination with CAV-2.² In addition, the CAV-2 strain used in Vanguard vaccines has been specially selected for freedom from oncogenic properties characteristic of adenoviruses.

Studies demonstrated that the CAV-2 fraction in Vanguard 5/CV-L not only aids in preventing ICH, but CAV-2 respiratory disease as well.³ Although conventional CAV-1 (ICH) vaccines cross-protect against CAV-2, they may not prevent subclinical infection and spread of the CAV-2 agent. Canine adenovirus type 2 challenge virus was not recovered from CAV-2-vaccinated dogs.

Safety of the CPV fraction in Vanguard 5/CV-L was demonstrated by oral administration of multiple doses of the vaccine strain to susceptible dogs, which remained normal. The CPV virus in Vanguard 5/CV-L shares a characteristic with other live CPV vaccine strains in that the vaccinal virus may be present in the feces following administration. Although this CPV vaccinal virus was found occasionally and in low titers in the feces of vaccinated dogs, testing demonstrated that the vaccine strain did not revert to virulence following six consecutive backpassages in susceptible dogs.

Safety of the CCV fraction in Vanguard 5/CV-L was assessed in a field trial in which 5,999 doses were administered. Postvaccinal reactions occurred in 0.78% of vaccinates. Stinging and pain was observed in 0.08% of vaccinates, transient lameness or swelling was observed in 0.28% of vaccinates, anaphylaxis was observed in 0.12% of vaccinates, and gastroenteritis was observed in 0.30% of vaccinates.

Efficacy of the CPV fraction in Vanguard 5/CV-L was demonstrated in challenge-of-immunity studies. Susceptible test dogs all developed CPV antibody titers after vaccination and were protected following oral administration of virulent CPV. Conversely, after challenge exposure, nonvaccinated control dogs all developed clinical signs of CPV enteritis, including vomiting and diarrhea with blood and mucous in the feces. Challenge virus was isolated from the feces of 5/5 control dogs, but only 1/20 vaccinates, and all controls developed marked lymphopenia, while lymphopenia was not demonstrated in vaccinates.

Further research demonstrated a stronger correlation of CPV immunogenicity to number of attenuating virus passages than to antigenic mass; immunogenicity of the vaccinal strain was shown to decline as the number of passages increased. The low-passage vaccinal virus Vanguard 5/CV-L is therefore highly immunogenic and capable of stimulating active immunity in the presence of maternal antibodies at the levels shown in Table 1. Studies demonstrating that capability involved forty-one 6- to 8-week old puppies (32 vaccinates and 9 controls) with the range of maternal antibody titers shown in Table 2. By 14 days after vaccination, 91% of vaccinates' titers were well above the protective threshold. By 21 days, all dogs, including the dog with the initial SN titer of 1:64 seroconverted, giving a group sero-conversion rate of 100%. In contrast, seropositive sentinel littermate dogs' CPV antibody titers declined, demonstrating that initial antibody titers were indeed of maternal origin and no adventitious exposure occurred during the study.

Table 1. Pre- And Postvaccination Serum Neutralization (sn) Titers

number Of Dogs	Prevaccination	Postvaccination
		7 Days	14 Days	21 Days
5	2	39.2	768.0	1433.6
2	4	3.0	36.0	192.0
11	8	45.1	457.5	488.7
9	16	33.8	263.1	739.6
4	32	40.0	450.0	640.0
1	64	32.0	32.0	128.0
Average	13.8	37.3	410.8	696.0

Table 2. Initial Serum Neutralization (SN) Titers of Vaccinates and Controls.

Sn Titers	# Vaccinates Included	# Controls Included
1:2	5	0
1:4	2	1
1:8	11	2
1:16	9	4
1:32	4	2
1:64	1	0

Efficacy of the CCV fraction in Vanguard 5/CV-L was demonstrated in a challenge-of-immunity study involving 20 vaccinated puppies and 10 controls. Twenty 6- to 7-week-old puppies received 1 dose of vaccine given by the subcutaneous route, followed by a second subcutaneous dose 21 days later. Vaccinates and controls were challenged with virulent CCV 21 days postvaccination. Puppies vaccinated with CCV demonstrated significant differences in reduction of clinical signs, virus shed, and reduction of diarrhea postchallenge when compared to the control group. There was a significant reduction of IFA detectable CCV antigen detected in the intestine at 19 days postchallenge in vaccinates compared to the control group. Serological responses of vaccinates were equal to or higher than the control group.

Directions

1. General Directions: Vaccination of healthy dogs is recommended. Aseptically rehydrate the freeze-dried vaccine (Vanguard 5/L) with the accompanying vial of liquid vaccine (FirstDose^® CV), shake well, and administer 1 mL subcutaneously or intramuscularly immediately after rehydration.

2. Primary Vaccination: Healthy dogs 6 weeks of age or older should receive 2 doses administered 3-4 weeks apart. If dogs are vaccinated before the age of 4 months, they should be revaccinated with a single dose upon reaching 4 months of age. (Maternal antibodies may interfere with development of an adequate immune response in puppies of less than 4 months old.)

3. Revaccination: Annual revaccination with a single dose is recommended.

Precautions

1. Store at 2°-7°C. Prolonged exposure to higher temperatures and/or direct sunlight may adversely affect potency. Do not freeze.

2. Use entire contents when first opened.

3. Sterilized syringes and needles should be used to administer the vaccine. Do not sterilize with chemicals because traces of disinfectant may inactivate the vaccine.

4. Burn containers and all unused contents.

5. Contains gentamicin as preservative.

6. Vaccination of pregnant bitches should be avoided.

7. As with many vaccines, anaphylaxis may occur after use. Initial antidote of epinephrine is recommended and should be followed with appropriate supportive therapy.

8. This product has been shown to be efficacious in healthy animals. A protective immune response may not be elicited if animals are incubating an infectious disease, are malnourished or parasitized, are stressed due to shipment or environmental conditions, are otherwise immunocompromised, or the vaccine is not administered in accordance with label directions.

References

1. Swango LJ: Frequently asked questions about CPV disease. Norden News 58:4-10, 1983.

2. Appel M, Bistner SI, Menegus M: Pathogenicity of low-virulence strains of two canine adenovirus types. Am J Vet Res 34:543-549, 1973.

3. Bass EP, Gill MA, Beckenhauer WH: Evaluation of a canine adenovirus type 2 strain as a replacement for infectious canine hepatitis vaccine. JAVMA 177:234-242, 1980.

Technical inquiries should be directed to Pfizer Animal Health Technical Services, (800) 366-5288 (USA), (800) 461-0917 (Canada).

For veterinary use only

U.S. Patent Nos. 4,567,042; 4,567,043; and 4,824,785

U.S. Veterinary License No. 189

Pfizer Animal Health, Exton, PA 19341, USA, Div. of Pfizer Inc, NY, NY 10017

75-4973-20

^® Registered trademark of Pfizer Products Inc; Pfizer Canada Inc., licensee

Presentation

Cartons of 25 x 1 dose vials.

Nac No.

11981112