BRONCHICINE CAe
Pfizer Animal Health
Bordetella Bronchiseptica Bacterin Cellular Antigen Extract

Contents:
BRONCHICINE CAe is a nonadjuvanted antigenic extract prepared from the cells of Bordetella bronchiseptica.
This product contains thimerosal (merthiolate) as a preservative.

Indications:
Recommended for use as an aid in the control of Canine Infectious Tracheobronchitis (Kennel Cough) caused by the organism represented.

Directions:
Shake well. Aseptically remove entire contents into the syringe. Push out any air trapped in the syringe. Administer 1 mL subcutaneously under loose skin (back of neck) to healthy dogs at least 8 weeks of age. Do not vaccinate into blood vessels. If blood enters the syringe choose another injection site. For initial vaccination a second dose is required 2-4 weeks later. This product should be administered by subcutaneous injection only. Annual revaccination with a single 1 mL dose is recommended.

Precaution(s):
Store at 35°F-45°F (2°C-8°C). Do not freeze. Use entire contents when first opened.

Caution(s):
Care should be taken to avoid microbial contamination of the product. In case of anaphylactoid reactions epinephrine should be administered immediately. Transient local irritation at the site of injection though rare may occur subsequent to use of this product.
For use in dogs only.

Discussion:
The effect of persisting B. bronchiseptica maternal antibody on the immune response in puppies to this bacterin has not been determined. Puppies from bitches immune to the organism usually have low antibody titers that are dissipated by 4-6 weeks of age. Although kennel cough is considered a disease of complex etiology it can be reproduced by challenge with B. bronchiseptica alone. A close association and/or confinement of dogs facilitates spread of the disease syndrome. Antibiotic therapy has been shown to be generally unsuccessful in reducing or eliminating B. bronchiseptica in dogs.

Presentation: 50 x 1 dose (1 mL) and 10 dose (10 mL) vials.

BRONCHICINE CAe
Pfizer Animal Health
Bordetella Bronchiseptica Bacterin Cellular Antigen Extract

Contents:
BRONCHICINE CAe is a nonadjuvanted antigenic extract prepared from the cells of Bordetella bronchiseptica.
This product contains thimerosal (merthiolate) as a preservative.

Indications:
Recommended for use as an aid in the control of Canine Infectious Tracheobronchitis (Kennel Cough) caused by the organism represented.

Directions:
Shake well. Aseptically remove entire contents into the syringe. Push out any air trapped in the syringe. Administer 1 mL subcutaneously under loose skin (back of neck) to healthy dogs at least 8 weeks of age. Do not vaccinate into blood vessels. If blood enters the syringe choose another injection site. For initial vaccination a second dose is required 2-4 weeks later. This product should be administered by subcutaneous injection only. Annual revaccination with a single 1 mL dose is recommended.

Precaution(s):
Store at 35°F-45°F (2°C-8°C). Do not freeze. Use entire contents when first opened.

Caution(s):
Care should be taken to avoid microbial contamination of the product. In case of anaphylactoid reactions epinephrine should be administered immediately. Transient local irritation at the site of injection though rare may occur subsequent to use of this product.
For use in dogs only.

Discussion:
The effect of persisting B. bronchiseptica maternal antibody on the immune response in puppies to this bacterin has not been determined. Puppies from bitches immune to the organism usually have low antibody titers that are dissipated by 4-6 weeks of age. Although kennel cough is considered a disease of complex etiology it can be reproduced by challenge with B. bronchiseptica alone. A close association and/or confinement of dogs facilitates spread of the disease syndrome. Antibiotic therapy has been shown to be generally unsuccessful in reducing or eliminating B. bronchiseptica in dogs.

Presentation: 25 x 1 dose (1 mL) and 10 dose (10 mL) vials.

Rabies vaccines not for sale in the states of AK AL AR CA CT GA HI IA ID IL IN KS MD ME MN MO MS MT NC ND NV NJ NM NY OR RI SC TX UT WA WV and WY. In addition some local laws require that a licensed veterinarian admminister rabies vaccine. Do Not order Rabies vaccine unless you find that you can legally administer the vaccine to your animals.

Defensor® 1
RabiesVaccine
Killed Virus
For use in dogs and cats

PRODUCT DESCRIPTION:
Defensor 1 is for vaccination of healthy dogs and cats 3 months of age or older as an aid in preventing rabies. The vaccine is prepared from cell-culture-grown chemically inactivated rabies virus. The seed virus is a highly immunogenic fixed strain of rabies virus which originated from Louis Pasteur’s original isolate in 1882. The inactivated virus is formulated with a highly purified adjuvant and is packaged in liquid form.

DISEASE DESCRIPTION:
Rabies is a worldwide high mortality disease affecting mammalian species. Wild animals are common vectors of the disease and the major source of transmission to humans and domestic animals. Despite successful attempts over the years to reduce the incidence of rabies recent published reports indicate that in the U.S. more than 30 000 people undergo treatment every year for possible exposure.1 Domestic animals are the major source of exposure for humans. Since 1980 the most commonly reported rabid domestic animals have been cats cattle and dogs. In 1990 a total of 4 881 cases of animal rabies were reported to the Center for Disease Control by all 50 states the District of Columbia and Puerto Rico.2 Susceptibility to rabies varies according to pet species. Rabies is not a treatable disease and suspect pets are usually quarantined until a clinical diagnosis is made at which time they are destroyed.
The route of infection can be oral respiratory or parenteral. Following infection a paralytic syndrome ensues emerging as either the "furious" or "dumb" form. "Furious rabies" is characterized by unusual aggression; "dumb rabies" by lethargy and a desire to avoid contact. Respiratory failure is the immediate cause of death.

SAFETY AND EFFICACY:
Because Defensor 1 is produced on an established cell line it has safety advantages over inactivated brain-origin rabies vaccines. Tissue-origin vaccines contain extraneous protein in addition to rabies antigen that can lead to autoimmune disease. The established cell line used in Defensor 1 has been extensively tested for freedom from contaminating agents. In addition use of an established cell line yields a vaccine of consistent potency from serial to serial. Defensor 1 has proven to be uniformly safe in experimental tests and no significant adverse reactions were reported in extensive clinical trials of the vaccine. A duration-of-immunity study conducted in accordance with federal regulation and under U.S. Department of Agriculture direction demonstrated that a 1-mL dose met federal guidelines for protection of dogs and cats against virulent challenge administered more than a year after vaccination.

DIRECTIONS:
General Directions: Shake well. Aseptically administer 1 mL subcutaneously. Dogs may be vaccinated intramuscularly or subcutaneously.
Primary Vaccination: Healthy dogs and cats should receive a single dose at 3 months of age or older. A repeat dose should be administered 1 year later.
Revaccination: Annual revaccination with a single dose is recommended.

PRECAUTIONS:
Store at 2° - 7°C. Prolonged exposure to higher temperatures may adversely affect potency. Do not freeze. Use entire contents when first opened. Sterilized syringes and needles should be used to administer this vaccine. Contains gentamicin as preservative. 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.

Presentation: 10-dose vials.

Rabies vaccines not for sale in the states of AK AL AR CA CT GA HI IA ID IL IN KS MD ME MN MO MS MT NC ND NV NJ NM NY OR RI SC TX UT WA WV and WY. In addition some local laws require that a licensed veterinarian admminister rabies vaccine. Do Not order Rabies vaccine unless you find that you can legally administer the vaccine to your animals.

Defensor® 3
Vaccine
Rabies Vaccine Killed Virus

Description:
The vaccine is prepared from cell-culture-grown chemically inactivated rabies virus. The seed virus is a highly immunogenic fixed strain of rabies virus which originated from Louis Pasteur's original isolate in 1882. The inactivated virus is formulated with a highly purified adjuvant and is packaged in liquid form.
Contains gentamicin as preservative.

Indications:
Defensor 3 is for vaccination of healthy dogs cats cattle and sheep 3 months of age or older as an aid in preventing rabies.

Precaution(s):
Store at 2°-7°C. Prolonged exposure to higher temperatures may adversely affect potency. Do not freeze.
Use entire contents when first opened.
Sterilized syringes and needles should be used to administer this vaccine.

Caution(s):
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):
Do not vaccinate within 21 days before slaughter.
For use in dogs cats cattle and sheep only.

Presentation: 10-dose vial.

Formerly known as Felocell RESP-2 now will be labeled as Felocell FVR C.
Vaccine

Feline Rhinotracheitis-Calici Vaccine Modified Live Virus

Description:
Felocell FVR C contains attenuated strains of feline rhinotracheitis virus and calicivirus propagated on established cell lines. Felocell FVR C is packaged in freeze-dried form with inert gas in place of vacuum. Contains gentamicin as preservative.

Indications:
Felocell FVR C is for vaccination of healthy cats as an aid in preventing feline viral rhinotracheitis (FVR) caused by feline herpesvirus-1 and feline respiratory disease caused by feline calicivirus (FCV).

Directions:

1. General Directions: Vaccination of healthy cats is recommended. Aseptically rehydrate the freeze-dried vaccine with the sterile diluent provided shake well and administer 1 mL intramuscularly or subcutaneously.
   
   
   
   
2. Primary Vaccination: Healthy cats 12 weeks of age or older should receive 2 doses administered 3-4 weeks apart. Cats vaccinated at less than 12 weeks of age should be revaccinated at 12 weeks of age.
   
   
   
   
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 queens 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.
For use in cats only.

Presentation: 25 x 1 dose vials.

Felocell 3
Vaccine
Formally FELOCELL CVR

Feline Rhinotracheitis-Calici-Panleukopenia Vaccine Modified Live Virus.

Description:
Felocell 3 contains attenuated strains of feline rhinotracheitis virus calicivirus and panleukopenia virus (Johnson Snow Leopard strain) propagated on established cell lines. Felocell 3 is packaged in freeze-dried form with inert gas in place of vacuum. Contains gentamicin as preservative.

Indications:
Felocell 3 is for vaccination of healthy cats as an aid in preventing feline viral rhinotracheitis (FVR) caused by feline herpesvirus-1 feline respiratory disease caused by feline calicivirus (FCV) and feline panleukopenia (FPL) caused by feline parvovirus.

Directions:

1. General Directions: Vaccination of healthy cats is recommended. Aseptically rehydrate the freeze-dried vaccine with the sterile diluent provided shake well and administer 1 mL intramuscularly or subcutaneously.
   
   
   
   
2. Primary Vaccination: Healthy cats 12 weeks of age or older should receive 2 doses administered 3-4 weeks apart. Cats vaccinated at less than 12 weeks of age should be revaccinated at 12 weeks of age.
   
   
   
   
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 queens 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.
For use in cats only.

Presentation: 25 x 1 dose vials.

Felocell 4
Vaccine
Formally FELOCELL CVR-C

Feline Rhinotracheitis-Calici-Panleukopenia-Chlamydia Psittaci Vaccine Modified Live Virus Chlamydia.

Description:
Felocell 4 contains attenuated strains of feline rhinotracheitis virus calicivirus and panleukopenia virus (Johnson Snow Leopard strain) and Chlamydia psittaci propagated on established cell lines. Felocell 4 is packaged in freeze-dried form with inert gas in place of vacuum. Contains gentamicin as preservative.

Indications:
Felocell 4 is for vaccination of healthy cats as an aid in preventing feline viral rhinotracheitis (FVR) caused by feline herpesvirus-1 feline respiratory disease caused by feline calicivirus (FCV) feline panleukopenia (FPL) caused by feline parvovirus and feline chlamydiosis caused by C. psittaci.

Directions:

1. General Directions: Vaccination of healthy cats is recommended. Aseptically rehydrate the freeze-dried vaccine with the sterile diluent provided shake well and administer 1 mL intramuscularly or subcutaneously.
   
   
   
   
2. Primary Vaccination: Healthy cats 12 weeks of age or older should receive 2 doses administered 3-4 weeks apart. Cats vaccinated at less than 12 weeks of age should be revaccinated at 12 weeks of age.
   
   
   
   
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 queens should be avoided.
For use in cats only.
For veterinary use only.

Presentation: 25 x 1 dose vials.

Leukocell 2
Vaccine

Feline Leukemia Vaccine Killed Virus

Description:
Leukocell 2 is prepared by propagating FeLV subgroups A B and C in FeLV-transformed lymphoid cells. Viral antigens are chemically inactivated combined with a sterile adjuvant to enhance the immune response and packaged in liquid form.
Leukocell 2 is prepared from an FeLV-transformed lymphoid cell line that releases FeLV viral particles which are soluble in a cell culture medium.1 The practical benefit of this unique patented feature is that production of immunosuppressive effects characteristic of fully assembled FeLV antigens whether live or killed is reduced.2-4 (See Safety and Efficacy). Contains gentamicin as preservative.

Indications:
Leukocell 2 is a multiple viral antigen vaccine for vaccination of healthy cats 9 weeks of age or older as an aid in preventing persistent viremia lymphoid tumors caused by feline leukemia virus (FeLV) and diseases associated with FeLV infection.

Directions:

1. General Directions: Shake well. Aseptically administer 1 mL subcutaneously.
   
   
   
   
2. Primary Vaccination: Healthy cats 9 weeks of age or older should receive 2 doses administered 3-4 weeks apart.
   
   
   
   
3. Revaccination: Annual revaccination with a single dose is recommended.
   
   
   
   

Precaution(s):
Store at 2°-7°C. Prolonged exposure to higher temperatures may adversely affect potency. Do not freeze. Use entire contents when first opened.Sterilized syringes and needles should be used to administer this vaccine.

Caution(s):
Certain postvaccination reactions may occur. (See Safety and Efficacy)
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 malnouished 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 veterinary use only.

Presentation: Cartons of 50 x 1 dose vials.

VANGUARD® B (IN)
Pfizer Animal Health
Bordatella Brnchiseptica Vaccine
Avirulent Live Culture

Product Description:
Vanguard B (IN) is for vaccination of healthy dogs and puppies at least 3 weeks of age or older as an aid in preventing kennel cough caused by Bordetella bronchiseptica. Vanguard B (IN) is composed of an avirulent live culture of B. bronchiseptica bacteria.

Disease Description:
B. bronchiseptica is considered to be one of the primary etiologic agents of canine infectious tracheobronchitis. The vaccination of dogs with live avirulent B. bronchiseptica has been demonstrated to greatly reduce the severity of the disease. The advantages of Vanguard B (IN) include: 1) induction of good local immune response, 2) competitive inhibition of colonization of wild-type bacteria, 3) administration of a single dose, and 4) lack of administration site reaction.

Safety and Efficacy:
The safety of Vanguard B (IN) was demonstrated by in-house and field safety studies. A total of 655 dogs were vaccinated according to label recommendations. One of the 655 vaccinates was reported to have intermittent sneezing for 2 days following vaccination. No treatment was required. None of the remaining 654 dogs had any adverse reaction to the vaccination.
A challenge model was used to evaluate the efficacy of Vanguard B (IN). The antigen blockage effect was also determined of a modified live canine parainfluenza virus (CPI) vaccine administered concurrently.
A total of 42 puppies 3-5 weeks old were used for the study. Twelve were vaccinated with a monovalent B. bronchiseptica vaccine, 20 were vaccinated with a B. bronchiseptica/CPI combination vaccine, and 10 were vaccinated with a CPI vaccine. The group receiving the monovalent CPI served as the control group for B. bronchiseptica challenge and the group vaccinated with monovalent B. bronchiseptica vaccine served as the control group for the CPI challenge. The route of vaccination for all vaccines was intranasal. Blood and tracheal swabs were taken on the day of vaccination and weekly thereafter. Three weeks after vaccination, all dogs were challenged with virulent B. bronchiseptica and observed for clinical signs of tracheobronchitis (presence of coughing) for 2 weeks. None of the dogs vaccinated with B. bronchiseptica developed tracheobronchitis after challenge whereas the control dogs (CPI vaccinates) showed clinical signs which were frequently observed during the first week after challenge.

Directions:
Preparation of the Vaccine: Rehydrate with the accompanying sterile diluent. Shake well and draw back into the syringe the required amount. Remove the needle from the syringe and attach the enclosed applicator tip. Use immediately.

Dosage and Administration:
Instill 0.5 mL of rehydrated vaccine into each nostril using a syringe with applicator tip. Annual revaccination is recommended.

Precautions:

1. This product is designed for intranasal use only with the enclosed applicator tip.
   
   
   
   
2. DO NOT VACCINATE DOGS PARENTERNALLY.
   
   
   
   
3. Store in the dark at 2°-7°C (35º-45ºF).
   
   
   
   
4. Shake well after rehydration.
   
   
   
   
5. Burn containers and all unused contents.
   
   
   
   
6. In case of anaphylactoid reaction, administer epinephrine.
   
   
   
   

Presentation: 25 x 1 dose vials.

VANGUARD CV
Pfizer Animal Health
Canine Coronavirus Vaccine
Killed Virus
For use in dogs only

Description:
Vanguard CV is for vaccination of healthy dogs 6 weeks of age or older as an aid in preventing canine coronaviral gastroenteritis caused by canine coronavirus (CCV). The product is a liquid preparation of inactivated CCV propagated on an established cell line with an adjuvant to enhance the immune response.

Disease Description:
CCV causes enteric disease in susceptible dogs of all ages worldwide. 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 or by environmental stress.1 Primary signs of CCV infection include depression, anorexia, fever, 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. Particularly in puppies, dehydration is a potentially life-threatening result of severe diarrhea with death loss occasionally occurring within 24-36 hours after onset of disease.2 With CCV infection most dogs remain afebrile or have subnormal body temperature, and leukopenia is rarely observed in uncomplicated cases.3
Laboratory procedures are frequently employed to differentiate CCV and canine parvovirus (CPV) 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 CCV or CPV 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. Initial widespread prevalence of CPV, combined with the ambiguities of the HA test, may have obscured the prevalence of CCV as a source of canine enteritides. Comprehensive protection thus requires vaccination for both CCV and CPV.

Safety and Efficacy:
Safety of Vanguard CV 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 Vanguard CV 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. Shake well. Aseptically administer 1 mL subcutaneously or intramuscularly.
   
   
   
   
2. Primary Vaccination:Healthy dogs 6 weeks of age or older should receive 2 doses administered 2-3 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 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 may adversely affect potency. Do not freeze.
   
   
   
   
2. Use entire contents when first opened.
   
   
   
   
3. Contains gentamicin as preservative.
   
   
   
   
4. Vaccination of pregnant bitches should be avoided.
   
   
   
   
5. As with many vaccines, anaphylaxis may occur after use. Initial antidote of epinephrine is recommended and should be followed with appropriate supportive therapy.
   
   
   
   
6. 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.
   
   
   
   

Presentation: Cartons of 50 x 1 dose vials of vaccine.

Formerly known as Vanguard DA2MP now will be labeled as Vanguard DAMP.

Vanguard DAMP
Vaccine
Canine Distemper-Adenovirus Type 2-Measles-Parainfluenza Vaccine Modified Live Virus

Description:
Vanguard DAMP contains highly attenuated strains of CD virus measles virus CAV-2 and CPI virus propagated on an established canine cell line and freeze-dried to preserve stability.
Contains penicillin and streptomycin as preservatives.

Indications:
Vanguard DAMP is for vaccination of healthy dogs 6 to 12 weeks of age 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) and canine parainfluenza caused by canine parainfluenza (CPI) virus.

Directions:

1. General Directions: Vaccination of healthy dogs 6 to 12 weeks of age is recommended. Aseptically rehydrate the freeze-dried vaccine with the sterile diluent provided shake well and administer 1 mL intramuscularly.
   
   
   
   
2. Primary Vaccination: Administer a single 1-mL dose to healthy dogs between 6 and 12 weeks of age.
   
   
   
   
3. Revaccination: Dogs should be revaccinated at 14 to 16 weeks of age with a canine distemper canine adenovirus type 2 and canine parainfluenza vaccine. In most cases a complete immunization program will also include vaccination for canine parvovirus Leptospira canicola and L. icterohaemorrhagiae. At the discretion of the veterinarian annual revaccination with a single dose against any or all of these pathogens is recommended.
   
   
   
   

Precaution(s):
Store at 2-7C. 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.

Presentation: Cartons of 25 x 1 dose vials.

Formerly known as Vanguard DA2P now will be labeled as Vanguard DAP.

VANGUARD DAP
Pfizer Animal Health
Canine Distemper-Adenovirus Type 2-Parainfluenza Vaccine
Modified Live Virus
For use in dogs only

PRODUCT DESCRIPTION:
Vanguard DAP is for vaccination of healthy dogs 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), and canine parainfluenza caused by canine parainfluenza (CPI) virus. Vanguard DA2P contains attenuated strains of CD virus, CAV-2, and CPI virus propagated on an established canine cell line and freeze-dried to preserve stability.

SAFETY AND EFFICACY:
Safety of Vanguard DAP was confirmed in laboratory and field tests.1 In more than 15,000 vaccinated dogs, no significant postvaccination reactions attributable to the vaccine were reported. These findings are particularly important since adverse side effects sometimes follow vaccination with modified live ICH vaccine. After vaccination with ICH vaccine, persistent kidney infections may occur, causing virus shedding in urine. Uveitis and corneal opacity also are occasionally observed 1-2 weeks after vaccination.2 Vaccination with the CAV-2 fraction in Vanguard DAP, however, produced no such lesions. Challenge virus was not recovered from vaccinated dogs, and was not isolated from tissues taken at necropsy. Ocular lesions were not observed in any of 172 dogs inoculated intravenously with multiple doses of CAV-2 vaccine virus, while intravenous inoculation of 32 dogs with ICH vaccine produced ocular lesions in 22%. Additionally, the strain of CAV-2 in this product has been shown free of oncogenic properties characteristic of canine adenovirus.
Efficacy of Vanguard DAP was demonstrated in challenge-of-immunity studies.1 Dogs vaccinated with the CAV-2 vaccine were completely protected against challenge with virulent ICH virus that produced clinical disease in 100% of nonvaccinated control dogs. Vaccinates were also protected against challenge with virulent CAV-2 that caused severe respiratory syndromes in susceptible controls. After challenge with virulent CD virus, 95% of dogs vaccinated with the CD vaccine remained healthy. In contrast, all nonvaccinated control dogs developed clinical signs of CD, and 80% died. After challenge with virulent CPI virus, no clinical signs of disease were observed among dogs vaccinated with CPI vaccine, while all nonvaccinated controls revealed clinical signs and severe lung lesions typical of CPI.

DURATION OF SEROLOGIC RESPONSE:
In dogs vaccinated and boostered as puppies, and then vaccinated again approximately 1 year later, revaccination with Vanguard DAP has been demonstrated (under field conditions) to result in serum antibody titers that persist for 12—48 months against CD virus (serum neutralization [SN] titer ¥ 1:32), CAV-1 (SN ¥ 1:16), CAV-2 (SN ¥ 1:16) and CPI virus (SN ¥ 1:16).
Protection against infectious agents involves a complex interplay between humoral immunity, cellular immunity, or a combination of both. The purpose of vaccination is to induce effector cells in both these arms of the immune system. During the process, long-term immunity in the form of memory and B lymphocytes is produced. Memory cells and antibodies interact to provide protection to an animal challenged with the same pathogen at a later date. Depending on the vaccine and the disease, antibodies may be produced that provide complete protection from disease and prevent or reduce shedding. In other cases, antibodies may play a minor or ineffective role and protection from disease relies on systemic, local cellular immunity and/or local antibody production. The role of sustained serological titers in the prevention of disease has not been confirmed.
In companion animals, immunological response to infection or vaccination has generally been evaluated by measuring the level of antibodies in serum and correlating these with protection or susceptibility. For the diseases caused by canine distemper virus, canine parvovirus,3,4 canine adenovirus and leptospirosis,3 evaluation of antibody titers may be a valuable diagnostic indicator to determine when revaccination may be needed. For other diseases, a serological response has not been identified that correlates with protection. Practical knowledge of the disease, the vaccine and the patient, along with serologic test results when appropriate, is paramount in making the best recommendation for a vaccination protocol for a specific animal.
The duration and character of the immune response to the viral antigens of Vanguard and/or Vanguard Plus were determined in a multi-center serology study involving 46 small animal veterinary clinics located in the United States (44) and Canada (2). Three hundred twenty-two male and female (intact and neutered) dogs of various ages, breeds, weights, lifestyles and time since last vaccination were enrolled in the study. Dogs were required to be healthy, greater than 2 years old with no history of disease due to CDV, CPV, CAV-1, CAV-2, or CPI and must not have been vaccinated for 12—48 months or longer. Additionally, dogs must have received at least a priming vaccination series approximately 2—7 weeks apart as a puppy and a booster vaccination approximately 8—16 months later. All previously administered vaccines were Vanguard products. A blood sample was collected from each dog and serum submitted to Cornell Veterinary Diagnostic Laboratory for determination of CDV (SN), CPV (HAI) titers, CAV-1 (SN), CAV-2 (SN), and CPI (SN). The samples were sent to a single diagnostic laboratory, thus ensuring a standardized test and methodology. As shown in the table below, elevated geometric mean titers were sustained for 12 to ¥ 48 months after the last booster. Since the study was conducted under field conditions with client-owned animals, it is possible that natural exposure to infectious agents could have occurred without clinical signs of infection. In such cases, the titers measured in the study could be the result of exposure to the disease in addition to vaccinations during the course of the study.

table 1. Geometric mean titer/number of dogs5

1. General Directions: Vaccination of healthy dogs is recommended. Aseptically rehydrate the freeze-dried vaccine with the sterile diluent provided, shake well, and administer 1 mL subcutaneously or intramuscularly.
   
   
   
   
   
2. Primary Vaccination: Healthy dogs should receive 2 doses administered 3-4 weeks apart. If dogs are vaccinated before the age of 4 months, they should be revaccinated upon reaching 4 months of age. (Maternal antibodies may interfere with development of an adequate immune response in puppies less than 4 months old.)
   
   
   
   
   
3. Revaccination: Annual revaccination with a single dose is recommended, although, as recommended by the American Veterinary Medical Association and its Council on Biologic and Therapeutic Agents, the attending veterinarian should determine the frequency of revaccination based on the animal’s lifestyle and risk of exposure.6
   
   
   
   

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.
   
   
   
   

For vaccination of healthy dogs 6 weeks of age or older as an aid in preventing leptospirosis caused by Leptospira canicola, L. grippotyphosa, L. icterohaemorrhagiae, and L. pomona.

Directions:
Aseptically rehydrate the freeze-dried vaccine (Vanguard L4) with the sterile gel provided, shake well, and administer 1 mL subcutaneously or intramuscularly. Healthy dogs should receive 2 doses administered 3-4 weeks apart. Dogs vaccinated before the age of 4 months should be revaccinated with a single dose at 4 months of age. Annual revaccination with a single dose is recommended.

Precautions:
Store at 2°-7°C. Do not freeze. Use entire contents when first opened. Sterilized syringes and needles should be used to administer this vaccine. Contains gentamicin as preservative.
Vaccination of pregnant bitches should be avoided. In case of anaphylaxis, administer epinephrine or equivalent.

Presentation: 25 1-dose vials of vaccine, rehydrate each to 1 mL
25 1-mL vials of sterile gel for use as diluent

Description:
Vanguard Plus CPV contains a strain of CPV attenuated by low passage on an established canine cell line. The vaccine is high titer (107.0 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. Some puppies in the field may have higher levels of maternal antibodies than those evaluated in our pivotal efficacy study. Vanguard Plus PV is packaged in liquid form.
Contains penicillin, streptomycin, and amphotericin B as preservatives.

Indications:
Vanguard® Plus CPV is for vaccination of healthy dogs 6 weeks of age or older for the prevention of canine parvoviral enteritis caused by 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.
For use in dogs only.

Vanguard Plus 5
Vaccine
Canine Distemper-Adenovirus Type 2-Parainfluenza-Parvovirus Vaccine, Modified Live Virus

Description:
Vanguard® Plus 5 contains attenuated strains of CD virus, CAV-2, CPI virus, and CPV propagated on an established canine cell line. The CPV fraction is high titer (107.0 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. Some puppies in the field may have higher levels of maternal antibodies than those evaluated in our pivotal efficacy study. Vanguard® Plus 5 is packaged in freeze-dried form with inert gas in place of vacuum.
Contains penicillin and streptomycin as preservatives.

Indications:
Vanguard® Plus 5 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, and canine parvoviral enteritis caused by canine parvovirus (CPV).

Directions:
1. General Directions: Vaccination of healthy dogs is recommended. Aseptically rehydrate the freeze-dried vaccine with the sterile diluent provided, 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.

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.
For use in dogs only.

Vanguard Plus 5/CV
Vaccine
Canine Distemper-Adenovirus Type 2-Coronavirus-Parainfluenza-Parvovirus Vaccine, Modified Live and Killed Virus

Description:
Vanguard® Plus 5/CV is a freeze-dried preparation of attenuated strains of CD virus, CAV-2, CPI virus, and CPV, plus a liquid preparation of inactivated CCV with an adjuvant. The CPV fraction is high titer (>107.0 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. Some puppies in the field may have higher levels of maternal antibodies than those evaluated in our pivotal efficacy study. All viruses were propagated on established cell lines. The liquid component is used to rehydrate the freeze-dried component, which is packaged with inert gas in place of vacuum.
Contains penicillin and streptomycin as preservatives.

Indications:
Vanguard® Plus 5/CV 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, and enteritis caused by canine coronavirus (CCV) and canine parvovirus (CPV).

Directions:
1. General Directions: Vaccination of healthy dogs is recommended. Aseptically rehydrate the freeze-dried vaccine (Vanguard Plus 5) 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.
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.

Presentation: 25 x 1 dose vials with accompanying bacterin diluent.

VANGUARD PLUS 5 L4
Pfizer Animal Health
Canine Distemper-Adenovirus Type 2-Parainfluenza-Parvovirus Vaccine
Modified Live Virus
Leptospira Canicola-Grippotyphosa-Icterohaemorrhagiae-Pomona Bacterin
For use in dogs only

PRODUCT DESCRIPTION:
Vanguard Plus 5 L4 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 parvovirus (CPV), and leptospirosis caused by Leptospira canicola, L. grippotyphosa, L. icterohaemorrhagiae, and L. pomona. Vanguard Plus 5 L4 is a freeze-dried preparation of attenuated strains of CD virus, CAV-2, CPI virus, CPV, and inactivated whole cultures of L. canicola, L. grippotyphosa, L. icterohaemorrhagiae, and L. pomona. These whole Leptospira cells have been extensively rinsed, resulting in reduced extraneous materials.
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 below. Some puppies in the field may have higher levels of maternal antibodies than those evaluated in our pivotal efficacy study. All viruses were propagated on established cell lines. An adjuvanted sterile gel is used to rehydrate the freeze-dried component, which is packaged with inert gas in place of vacuum.

SAFETY AND EFFICACY:
Laboratory evaluation demonstrated that Vanguard Plus 5 L4 aided in preventing disease caused by CD, CAV-1, CAV-2, CPI, and CPV, and leptospirosis caused by L. canicola, L. grippotyphosa, L. icterohaemorrhagiae, and L. pomona, and that no immunologic interference existed among the vaccine fractions. Field safety trials conducted by Pfizer Animal Health showed it to be safe 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. 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 the CAV-2 strain used in Vanguard vaccines not only protects against ICH, but against CAV-2 respiratory disease as well.¹ 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 L4 was subjected to comprehensive safety and efficacy testing at Pfizer. It was shown safe and essentially reaction-free in laboratory tests and in clinical trials under field conditions. Product safety was further demonstrated by a backpassage study that included oral administration of multiple doses of the vaccine strain to susceptible dogs, all of which remained normal. The CPV virus in Vanguard Plus 5 L4 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 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.^2,3 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)]. 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). 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 L4 is therefore highly immunogenic and capable of stimulating active immunity in the presence of maternal antibodies.

DURATION OF SEROLOGIC RESPONSE:
In dogs vaccinated and boostered as puppies, and then vaccinated again approximately 1 year later, revaccination with Vanguard Plus 5 L4 has been demonstrated (under field conditions) to result in serum antibody titers that persist for 12-48 months against CD virus (serum neutralization [SN] titer = 1:32), CAV-1 (SN =1:16), CAV-2 (SN = 1:16), CPI virus (SN = 1:16), and CPV (hemagglutination inhibition [HAI] titer = 1:80).
Protection against infectious agents involves a complex interplay between humoral immunity, cellular immunity, or a combination of both. The purpose of vaccination is to induce effector cells in both these arms of the immune system. During the process, long-term immunity in the form of memory T and B lymphocytes is produced. Memory cells and antibodies interact to provide protection to an animal challenged with the same pathogen at a later date. Depending on the vaccine and the disease, antibodies may be produced that provide complete protection from disease and prevent or reduce shedding. In other cases, antibodies may play a minor or ineffective role and protection from disease relies on systemic, local cellular immunity and/or local antibody production. The role of sustained serological titers in the prevention of disease has not been confirmed.
In companion animals, immunological response to infection or vaccination has generally been evaluated by measuring the level of antibodies in serum and correlating these with protection or susceptibility. For the diseases caused by canine distemper virus, canine parvovirus,^4,5 canine adenovirus and leptospirosis,⁴ evaluation of antibody titers may be a valuable diagnostic indicator to determine when revaccination may be needed. For other diseases, a serological response has not been identified that correlates with protection. Practical knowledge of the disease, the vaccine and the patient, along with serologic test results when appropriate, is paramount in making the best recommendation for a vaccination protocol for a specific animal.
The duration and character of the immune response to the viral antigens of Vanguard and/or Vanguard Plus were determined in a multi-center serology study involving 47 small animal veterinary clinics located in the United States (44) and Canada (3). Three hundred twenty-two male and female (intact and neutered) dogs of various ages, breeds, weights, lifestyles and time since last vaccination were enrolled in the study. Dogs were required to be healthy, greater than 2 years old with no history of disease due to CDV, CPV, CAV-1, CAV-2, or CPI and must not have been vaccinated for 12-48 months or longer. Additionally, dogs must have received at least a priming vaccination series approximately 2-7 weeks apart as a puppy and a booster vaccination approximately 8-16 months later. All previously administered vaccines were Vanguard products. A blood sample was collected from each dog and serum submitted to Cornell Veterinary Diagnostic Laboratory for determination of CDV (SN), CPV (HAI) titers, CAV-1 (SN), CAV-2 (SN), and CPI (SN). The samples were sent to a single diagnostic laboratory, thus ensuring a standardized test and methodology. As shown in the table below, elevated geometric mean titers were sustained for 12 to = 48 months after the last booster. Since the study was conducted under field conditions with client-owned animals, it is possible that natural exposure to infectious agents could have occurred without clinical signs of infection. In such cases, the titers measured in the study could be the result of exposure to the disease in addition to vaccinations during the course of the study.

table 1. Geometric mean titer/number of dogs⁶

DIRECTIONS:

1. General Directions: Vaccination of healthy dogs is recommended. Aseptically rehydrate the freeze-dried vaccine (Vanguard Plus 5 L4) with the sterile gel provided, 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, although, as recommended by the American Veterinary Medical Association and its Council on Biologic and Therapeutic Agents, the attending veterinarian should determine the frequency of revaccination based on the animal's lifestyle and risk of exposure.⁷
   
   
   
   

PRECAUTIONS:

1. Store at 2°-7°C. Prolonged exposure to higher temperatures and/or direct sunlight may adversely affect potency. Do not freeze./
   
   
   
   
2. 
   
   
   
   
3. Use entire contents when first opened.
   
   
   
   
4. Sterilized syringes and needles should be used to administer this vaccine. Do not sterilize with chemicals because traces of disinfectant may inactivate the vaccine.
   
   
   
   
5. Burn containers and all unused contents.
   
   
   
   
6. Contains gentamicin as preservative.
   
   
   
   
7. Vaccination of pregnant bitches should be avoided.
   
   
   
   
8. In case of anaphylaxis, administer epinephrine or equivalent.
   
   
   
   
9. 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. 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.
   
   
   
   
2. 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.
   
   
   
   
3. 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.
   
   
   
   
4. Schultz RD: Current and future canine and feline vaccination programs. Vet Med 93(3):233-254, 1998.
   
   
   
   
5. Tizard I, Ni Y: Use of serologic testing to assess immune status of companion animals. JAVMA 213:54-60, 1998.
   
   
   
   
6. Study 2164H-60-01-004, Pfizer Animal Health
   
   
   
   
7. American Veterinary Medical Association, Position Statements on Biologics, June 2001.
   
   
   
   

PRODUCT DESCRIPTION:
Vanguard Plus 5 L4 CV 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, L. grippotyphosa, L. icterohaemorrhagiae, and L. pomona. Vanguard Plus 5 L4 CV is a freeze-dried preparation of attenuated strains of CD virus, CAV-2, CPI virus, CPV, and inactivated whole cultures of L. canicola, L. grippotyphosa, L. icterohaemorrhagiae, and L. pomona. These whole Leptospira cells have been extensively rinsed, resulting in reduced extraneous materials.
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 below. Some puppies in the field may have higher levels of maternal antibodies than those evaluated in our pivotal efficacy study. All viruses were propagated on established cell lines. A liquid preparation of inactivated CCV with an adjuvant is used to rehydrate the freeze-dried component, which is packaged with inert gas in place of vacuum.

SAFETY AND EFFICACY: Laboratory evaluation demonstrated that Vanguard Plus 5 L4 CV aided in preventing disease caused by CD, CAV-1, CAV-2, CPI, CCV and CPV, and leptospirosis caused by L. canicola, L. grippotyphosa, L. icterohaemorrhagiae, and L. pomona, and that no immunologic interference existed among the vaccine fractions. Field safety trials conducted by Pfizer Animal Health showed it to be safe 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. 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 the CAV-2 strain used in Vanguard vaccines not only protects against ICH, but against CAV-2 respiratory disease as well.¹ 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 L4 CV was subjected to comprehensive safety and efficacy testing at Pfizer. It was shown safe and essentially reaction-free in laboratory tests and in clinical trials under field conditions. Product safety was further demonstrated by a backpassage study that included oral administration of multiple doses of the vaccine strain to susceptible dogs, all of which remained normal. The CPV virus in Vanguard Plus 5 L4 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 the 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.^2,3 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)]. 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). 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 L4 CV is therefore highly immunogenic and capable of stimulating active immunity in the presence of maternal antibodies.
The efficacy of the CCV fraction of Vanguard Plus 5 L4 CV was demonstrated in an extensive vaccination challenge study. Sixteen 7- to 8-week-old puppies were vaccinated with Vanguard 5/CV-L (vaccinates) and 17 with Vanguard 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.

DURATION OF SEROLOGIC RESPONSE:
In dogs vaccinated and boostered as puppies, and then vaccinated again approximately 1 year later, revaccination with Vanguard Plus 5 L4 CV has been demonstrated (under field conditions) to result in serum antibody titers that persist for 12-48 months against CD virus (serum neutralization [SN] titer = 1:32), CAV-1 (SN = 1:16), CAV-2 (SN = 1:16), CPI virus (SN = 1:16), and CPV (hemagglutination inhibition [HAI] titer = 1:80).
Protection against infectious agents involves a complex interplay between humoral immunity, cellular immunity, or a combination of both. The purpose of vaccination is to induce effector cells in both these arms of the immune system. During the process, long-term immunity in the form of memory T and B lymphocytes is produced. Memory cells and antibodies interact to provide protection to an animal challenged with the same pathogen at a later date. Depending on the vaccine and the disease, antibodies may be produced that provide complete protection from disease and prevent or reduce shedding. In other cases, antibodies may play a minor or ineffective role and protection from disease relies on systemic, local cellular immunity and/or local antibody production. The role of sustained serological titers in the prevention of disease has not been confirmed.
In companion animals, immunological response to infection or vaccination has generally been evaluated by measuring the level of antibodies in serum and correlating these with protection or susceptibility. For the diseases caused by canine distemper virus, canine parvovirus,^4,5 canine adenovirus and leptospirosis,⁴ evaluation of antibody titers may be a valuable diagnostic indicator to determine when revaccination may be needed. For other diseases, a serological response has not been identified that correlates with protection. Practical knowledge of the disease, the vaccine and the patient, along with serologic test results when appropriate, is paramount in making the best recommendation for a vaccination protocol for a specific animal.
The duration and character of the immune response to the viral antigens of Vanguard and/or Vanguard Plus were determined in a multi-center serology study involving 47 small animal veterinary clinics located in the United States (44) and Canada (3). Three hundred twenty-two male and female (intact and neutered) dogs of various ages, breeds, weights, lifestyles and time since last vaccination were enrolled in the study. Dogs were required to be healthy, greater than 2 years old with no history of disease due to CDV, CPV, CAV-1, CAV-2, or CPI and must not have been vaccinated for 12-48 months or longer. Additionally, dogs must have received at least a priming vaccination series approximately 2-7 weeks apart as a puppy and a booster vaccination approximately 8-16 months later. All previously administered vaccines were Vanguard products. A blood sample was collected from each dog and serum submitted to Cornell Veterinary Diagnostic Laboratory for determination of CDV (SN), CPV (HAI) titers, CAV-1 (SN), CAV-2 (SN), and CPI (SN). The samples were sent to a single diagnostic laboratory, thus ensuring a standardized test and methodology. As shown in the table below, elevated geometric mean titers were sustained for 12 to = 48 months after the last booster. Since the study was conducted under field conditions with client-owned animals, it is possible that natural exposure to infectious agents could have occurred without clinical signs of infection. In such cases, the titers measured in the study could be the result of exposure to the disease in addition to vaccinations during the course of the study.

table 1. Geometric mean titer/number of dogs⁶

DIRECTIONS:

1. General Directions: Vaccination of healthy dogs is recommended. Aseptically rehydrate the freeze-dried vaccine (Vanguard Plus 5 L4) with the accompanying vial of liquid vaccine (Vanguard 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, although, as recommended by the American Veterinary Medical Association and its Council on Biologic and Therapeutic Agents, the attending veterinarian should determine the frequency of revaccination based on the animal's lifestyle and risk of exposure.⁷
   
   
   
   

PRECAUTIONS:

1. Store at 2°-°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. In case of anaphylaxis, administer epinephrine or equivalent.
   
   
   
   
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. 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.
   
   
   
   
2. 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.
   
   
   
   
3. 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.
   
   
   
   
4. Schultz RD: Current and future canine and feline vaccination programs. Vet Med 93(3):233-254, 1998.
   
   
   
   
5. Tizard I, Ni Y: Use of serologic testing to assess immune status of companion animals. JAVMA 213:54-60, 1998.
   
   
   
   
6. Study 2164H-60-01-004, Pfizer Animal Health
   
   
   
   
7. American Veterinary Medical Association, Position Statements on Biologics, June 2001.