Vanguard Plus 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 Plus 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 disease caused by canine adenovirus type 2 (CAV-2), canine parainfluenza caused by canine parainfluenza (CPI) virus, enteritis caused by canine coronavirus (CCV) and canine parvovirus (CPV), and leptospirosis caused by Leptospira canicola and L. icterohaemorrhagiae. Vanguard Plus 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. The CPV fraction is high titer (>10^7.0 TCID₅₀/dose) and was attenuated by low passage (35 passes from the canine isolate with a maximum of 2 additional passes allowed for production) in the canine cell line which gives it the immunogenic properties capable of overriding maternal antibody interference at the levels indicated in Table 2. Some puppies in the field may have higher levels of maternal antibodies than those evaluated in our pivotal efficacy study. All viruses were propagated in established cell lines. 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. In puppies 4-12 weeks of age CPV may occasionally cause myocarditis that can result in acute heart failure after a brief and inconspicuous illness. Following infection many dogs are refractory to the disease for a year or more. Similarly, seropositive bitches may transfer to their puppies CPV antibodies which can interfere with active immunization of the puppies through 16 weeks of age. CCV also causes enteric disease in susceptible dogs of all ages worldwide.² Highly contagious, the virus is transmitted primarily through direct contact with infectious feces, and may cause clinical enteritis within 1-4 days after exposure. Severity of disease may be exacerbated by concurrent infection with other agents.³ Primary signs of CCV infection include anorexia, vomiting, and diarrhea. Frequency of vomiting usually diminishes within a day or 2 after onset of diarrhea, but diarrhea may linger through the course of infection, and stools occasionally may contain streaks of blood. With CCV infection most dogs remain afebrile and leukopenia is not observed in uncomplicated cases.^2-4 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.

Safety And Efficacy

Laboratory evaluation demonstrated that Vanguard Plus 5/CV-L immunized dogs against CD, ICH, CAV-2 and CPI respiratory disease, enteritis caused by CCV and CPV infection, and leptospirosis caused by L. canicola and L. icterohaemorrhagiae, and that no immunologic interference existed among the vaccine fractions. Extensive field safety trials conducted by Pfizer Animal Health showed it to be safe with minimal reactions in dogs as young as 6 weeks of age under normal usage conditions.

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-2.⁵ In addition, the CAV-2 strain used in Vanguard vaccines has been specially selected for freedom from oncogenic properties characteristic of adenoviruses.

Studies conducted at Pfizer demonstrated that CAV-2 not only protects against ICH, but against CAV-2 respiratory disease as well.⁶ 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 in tests conducted at Pfizer.

The CPV fraction in Vanguard Plus 5/CV-L was subjected to comprehensive safety and efficacy testing at Pfizer. It was shown safe with minimal reactions in laboratory tests and in clinical trials under field conditions. Product safety was further demonstrated by a backpassage study which included oral administration of multiple doses of the vaccine strain to susceptible dogs, all of whom remained normal. The CPV virus in Vanguard Plus 5/CV-L shares a characteristic with other live CPV vaccine strains in that the vaccine virus may be present in the feces following administration. Although this CPV vaccine virus was found occasionally and in low titers in the feces of vaccinated dogs, testing demonstrated that the vaccine master seed did not revert to virulence following 6 consecutive backpassages in susceptible dogs.

Research at Pfizer demonstrated that 3 doses of the vaccine with increased CPV virus titer can overcome interfering serum neutralization (SN) titers associated with maternal antibody. Serum neutralization titers as low as 1:4 have been shown by others to interfere with active immunization using conventional modified live vaccines.^7,8 A clinical trial was conducted with fifty 6-week-old puppies [25 vaccinates (SN titer range <2-256) and 25 nonvaccinated controls (SN titer range 4-1024)] (Table 1). The group of vaccinates received 3 doses, with vaccinations administered 3 weeks apart beginning at 6 weeks of age. After 1 vaccination, 13/25 puppies exhibited a 4-fold or greater increase in CPV SN titer (seroconversion) (Table 2). Twelve of these 13 puppies had maternal SN titers ≤1:16 at the time of the first vaccination with the remaining puppy having an SN titer of 1:64. Another 9 puppies with initial SN titers between 1:16 and 1:256 seroconverted after the second vaccination. Their maternal antibody SN titers had declined to ≤1:64 at the time of the second vaccination. Similarly, the last 3 vaccinates, with initial SN titers of 1:128, seroconverted after the third vaccination, after their maternal antibody CPV titer dropped ≤1:64. Therefore, in this study, when 3 doses of vaccine were given beginning at 6 weeks of age, all 25 vaccinates, even those with the highest maternal antibody levels, became actively immunized (GM = 1:1176; range of SN titers 128-4096). All 50 dogs were challenged 3 weeks after the third vaccination with a heterologous CPV challenge virus. Fourteen of 25 nonvaccinated control dogs died or showed illness severe enough to warrant euthanasia, while all 25 vaccinates remained essentially healthy. The high-titer, low-passage vaccine virus in Vanguard Plus 5/CV-L is therefore highly immunogenic and capable of stimulating active immunity in the presence of maternal antibodies.

Table 1. Initial Serum Neutralization (sn) Titers Of Vaccinates And Controls

Table 2. Postvaccination Serum Neutralization (sn) Titers Geometric Mean (range)^a

^a dogs Were Vaccinated At 6, 9, And 12 Weeks Of Age.

^b pre-challenge Sn Titers

the Efficacy Of The Ccv Fraction Of Vanguard Plus 5/cv-l Was Demonstrated In An Extensive Vaccination Challenge Study. Sixteen 7- To 8-week-old Puppies Were Vaccinated With Vanguard Plus 5/cv-l (vaccinates) And 17 With Vanguard Plus 5/l (controls). All Puppies Received Three 1-ml Doses At 3-week Intervals. Three Weeks Following The Third Vaccination, Puppies Were Challenged With A Virulent Strain Of Ccv (cv-6). Clinical Observations, Temperatures, Weights, And Blood Parameters Were Monitored For 21 Days Following Infection. Ccv Vaccinates Demonstrated A Reduction In The Occurrence Of Diarrhea And Amount Of Virulent Ccv Shed When Compared To Controls. At 21 Days Postchallenge, Fluorescent Antibody Staining For Virulent Ccv Of Small Intestinal Sections Demonstrated A Significant Reduction (p<0.05) In Detectable Ccv Antigen Between Ccv Vaccinates And Controls (table 3).

table 3. Fluorescent Antibody Staining Of Small Intestinal Sections 21 Days Following Challenge

Directions

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

2. Primary Vaccination: Healthy dogs 6 weeks of age or older should receive 3 doses, each administered 3 weeks apart.

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 this 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. Tennant BJ, Gaskell RM, Jones RC: Studies on the epizootiology of canine coronavirus. Vet Rec 132:7-11, 1993.

3. Appel MJG: Does canine coronavirus augment the effects of subsequent parvovirus infection? Vet Med 83:360-366, 1988.

4. Carmichael LE, Binn LN: New enteric viruses in the dog. Advances in Vet Sci and Comp Med 25:1-35, 1981.

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

6. 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.

7. O'Brien SE, Roth JA, Hill BL: Response of pups to modified-live canine parvovirus component in a combination vaccine. JAVMA 188:699-701, 1986.

8. O'Brien SE: Serologic response of pups to the low-passage modified-live canine parvovirus-2 component in a combination vaccine. JAVMA 204:1207-1209, 1994.

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. 3,616,203; 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

75-5306-15

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

Presentation

25 x 1 dose vials with accompanying bacterin diluent.

Nac No.

11981173