VANGUARD® PLUS CPV/CV

Description: VANGUARD^® Plus CPV/CV is a liquid preparation of attenuated strains of CPV and 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) on 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. Both viruses were propagated on established cell lines.

Contains penicillin and streptomycin as preservatives.

Indications: VANGUARD^® Plus CPV/CV is for vaccination of healthy dogs 6 weeks of age or older as an aid in preventing enteritis caused by canine coronavirus (CCV) and canine parvovirus (CPV).

Directions:

1. General Directions: Vaccination of healthy dogs is recommended. Shake well. Aseptically 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.

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

Use entire contents when first opened.

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

Burn containers and all unused contents.

Caution(s): Vaccination of pregnant bitches should be avoided.

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

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.

Warning(s): For use in dogs only.

For veterinary use only.

Discussion: Disease Description: 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.¹ 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.² 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.^1-3

Trial Data: Safety and Efficacy: Laboratory evaluation demonstrated that VANGUARD^® Plus CPV/CV immunized dogs against enteritis caused by CCV and CPV infection, and that no immunologic interference existed between the vaccine fractions. Extensive field safety trials conducted by Pfizer Animal Health have shown the 2 fractions to be safe and essentially reaction-free in dogs as young as 6 weeks of age under normal usage conditions.

Safety of the CPV fraction 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 CPV/CV 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 a vaccine with increased CPV virus titer can overcome 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.^4,5 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 CPV/CV 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

^aDogs were vaccinated at 6, 9, and 12 weeks of age.

^bPre-challenge SN titers

The efficacy of the CCV fraction of VANGUARD^® Plus CPV/CV 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

References: Available upon request.

Presentation: 1 dose.

Product Information Provided by Pfizer Animal Health©