Duration of immunity induced by companion animal vaccines

Concerns about possible adverse effects from annual vaccination have prompted the reanalysis of vaccine protocols for cats and dogs. In the last decade, several veterinary advisory groups have published protocols that recommend extended revaccination intervals for certain 'core' vaccines. In addition, practicing veterinarians have been asked to consider vaccination as an individualized medical procedure, based on an analysis of risks and benefits for each vaccine in an individual animal. The calls for extended revaccination intervals prompted considerable debate in USA and internationally. Areas of concern include the amount of evidence to support prolonged immunity from various vaccines, the risk of poor responses in individual animals and the possible effects on population immunity. This review examines how the duration of immunity (DOI) to a vaccine is established in animals and humans. It reviews factors that can affect the DOI in an individual animal, including the types of immune defenses stimulated by the pathogen, and the vaccine, host factors such as age and the level of exposure to the pathogen. In addition, it examines DOI studies that were published for canine and feline core vaccines.     

Serological testing—An alternative to boosters?

The issue of the duration of immunity, particularly for the modified live viral components of veterinary vaccines, has been a significant part of the recent vaccination debate. One manufacturer has increased the recommended booster interval for these components to 3 years give name and another now states 'up to 4 years' immunity. There remain many unanswered questions regarding this duration of immunity (DOI). Studies suitable for data sheet claims are time consuming and costly and can only be performed in laboratory dogs under tightly controlled conditions. Evidence from rabies serology testing in the UK shows that the response of individual animals to routine vaccination is highly variable. Much of the published field evidence on the persistence of antibody titres originates from North America, where vaccination strategies and reservoir species differ from Europe. Quantifying the effect of exposure to field virus on the maintenance of immunity in these studies is impossible, and little is known of the circulation of virus in unvaccinated dogs and wild mammals throughout Europe. If owners or vets are concerned about revaccination one option is to assess the need for each booster by performing a blood test. There is some published evidence of the relationship between antibody titres and protective immunity, and tests are available to measure responses to individual viral components of the routine canine and feline vaccines. It must be remembered that most commercial tests to assess immunity only measure antibodies, which are only one aspect of the immune response to vaccination. It is therefore possible that animals without or with low antibody titres are in fact protected. Serological tests are an option if owners are unwilling to have their animal boostered without evidence that it is needed. However, the cost of these tests is likely to exceed that of booster vaccination for the foreseeable future.     

Three-year serologic immunity against canine parvovirus type 2 and canine adenovirus type 2 in dogs vaccinated with a canine combination vaccine

A group of client-owned dogs and a group of dogs at a commercial kennel were evaluated for duration of antibody responses against canine parvovirus type 2 (CPV-2) and canine adenovirus type 1 (CAV-1) after receiving a combination vaccine containing recombinant canarypox-vectored canine distemper virus (CDV) and modified-live CPV-2, CAV-2, and canine parainfluenza virus, with (C6) or without (C4) two serovars of Leptospira (Recombitek C4 or C6, Merial). Duration of antibody, which correlates with protective immunity, was found to be at least 36 months in both groups. Recombitek combination vaccines can confidently be given every 3 years with assurance of protection in immunocompetent dogs against CPV-2 and CAV-1 as well as CDV. This allows this combination vaccine, like other, similar modified- live virus combination products containing CDV, CAV-2, and CPV-2, to be administered in accordance with the recommendations of the American Animal Hospital Association Canine Vaccine Task Force.     

Use of modified live feline panleukopenia virus vaccine to immunize dogs against canine parvovirus

Modified live feline panleukopenia virus (FPLV) vaccine protected dogs against canine parvovirus (CPV) infection. However, unlike the long-lived (greater than or equal to 20-month) immunity engendered by CPV infection, the response of dogs to living FPLV was variable. Doses of FPLV (snow leopard strain) in excess of 10(5.7) TCID50 were necessary for uniform immunization; smaller inocula resulted in decreased success rates. The duration of immunity, as measured by the persistence of hemagglutination-inhibiting antibody, was related to the magnitude of the initial response to vaccination; dogs with vigorous initial responses resisted oronasal CPV challenge exposure 6 months after vaccination, and hemagglutination-inhibiting antibodies persisted in such dogs for greater than 1 year. Limited replication of FPLV in dogs was demonstrated, but unlike CPV, the feline virus did not spread to contact dogs or cats. Adverse reactions were not associated with living FPLV vaccination, and FPLV did not interfere with simultaneous response to attenuated canine distemper virus.     

Polymerase chain reaction (PCR) amplification of parvoviral DNA from the brains of dogs and cats with cerebellar hypoplasia

Cerebellar hypoplasia in cats is caused most commonly by an in utero or perinatal infection with feline panleukopenia virus (parvovirus). Cerebellar hypoplasia has been reported infrequently in dogs, but no viral etiology has been identified to date. DNA was extracted from archival, paraffin-embedded, cerebellar tissue from 8 cats and from 2 canine littermates with cerebellar hypoplasia, 2 canine littermates with cerebellar cortical abiotrophy, 6 dogs with congenital cerebellar vermal defects, 1 dog with congenital hydranencephaly, and 15 dogs and cats with various encephalitdes. The DNA extracted from each cerebellum was subject to polymerase chain reaction (PCR) amplification by 3 primer pairs specific for parvovirus DNA. Sequence analysis of PCR products from each of the 8 cats and 2 dogs with cerebellar hypoplasia confirmed their identity with parvoviral DNA. The 6 dogs with cerebellar vermal defects, 2 dogs with cortical abiotrophy, 1 dog with congenital hydranencephaly, and all control samples were PCR negative for parvovirus. Parvoviral structural proteins were not identified by immunohistochemistry in either dog with cerebellar hypoplasia. This study shows that parvoviral DNA can be amplified from feline and canine archival brain tissue and that cerebellar hypoplasia in dogs might be associated with in utero parvovirus infection.     

Development of a Vaccine Incorporating Killed Virus of Canine Origin for the Prevention of Canine Parvovirus Infection

A parvovirus of canine origin, cultured in a feline kidney cell line, was inactivated with formalin. Three pilot serials were produced and three forms of finished vaccine (nonadjuvanted, single adjuvanted and double adjuvanted) were tested in vaccination and challenge trials. A comparison was also made with two inactivated feline panleukopenia virus vaccines, one of which has official approval for use in dogs. The inactivated canine vaccine in nonadjuvanted, adjuvanted or double adjuvanted form was immunogenic in 20 of 20 vaccinated dogs. The double adjuvanted vaccine is selected as the one of choice on the basis of best and most persistent seriological response.     

Duration of serologic response to five viral antigens in dogs

OBJECTIVE: To determine whether vaccinated dogs either remained seropositive or responded serologically to revaccination for 5 key viral antigens after extended periods since their last vaccination. DESIGN: Serologic survey. ANIMALS: 322 healthy client-owned dogs. PROCEDURE: Dogs were > or = 2 years old and vaccinated against canine distemper virus (CDV), canine adenovirus-1 (CAV-1), canine adenovirus-2 (CAV-2), canine parainfluenza virus (CPIV), and canine parvovirus (CPV). On day 0, dogs were revaccinated with a vaccine from the same vaccine line as they had historically received. Antibody titers were measured in sera collected at day 0 (prevaccination titer) and 5 to 7 days later (postvaccination titer). Dogs were considered to have responded serologically if they had a day-0 serum neutralization titer to CDV > or = 1:32; a serum neutralization titer to CAV-1, CAV-2, or CPIV > or = 1:16; a hemagglutination inhibition titer to CPV > or = 1:80; or a > or = 4-fold increase in antibody titer after revaccination. RESULTS: The percentage of dogs that had titers at or greater than the threshold values or responded to revaccination with a > or = 4-fold increase in titer was 98.1% for CDV, 98.4% for CAV-1, 99.0% for CAV-2, 100% for CPIV, and 98.1% for CPV. CONCLUSIONS AND CLINICAL RELEVANCE: In most dogs, vaccination induced a response that lasted up to and beyond 48 months for all 5 antigens. Although not equivalent to challenge-of-immunity studies as a demonstration of efficacy, results suggest that revaccination with the same vaccine provides adequate protection even when given less frequently than the traditional 1-year interval. The study provides valuable information for clinicians to help determine appropriate revaccination intervals.     

Dog response to inactivated canine parvovirus and feline panleukopenia virus vaccines

Inactivated canine parvovirus (CPV) and inactivated feline panleukopenia virus (FPV) vaccines were evaluated in dogs. Maximal serologic response occurred within 1-2 weeks after vaccination. Antibody titers then declined rapidly to low levels that persisted at least 20 weeks. Immunity to CPV, defined as complete resistance to infection, was correlated with serum antibody titer and did not persist longer than 6 weeks after vaccination with inactivated virus. However, protection against generalized infection was demonstrated 20 weeks after vaccination. In unvaccinated dogs, viremia and generalized infection occurred after oronasal challenge with virulent CPV. In contrast, viral replication was restricted to the intestinal tract and gut-associated lymphoid tissue of vaccinated dogs. Canine parvovirus was inactivated by formalin, beta-propiolactone (BPL), and binary ethylenimine (BEI) in serum-free media; inactivation kinetics were determined. Formalin resulted in a greater loss of viral HA than either BEI of BPL, and antigenicity was correspondingly reduced.     

Three-year duration of immunity in dogs following vaccination against canine adenovirus type-1, canine parvovirus, and canine distemper virus

A challenge-of-immunity study was conducted to demonstrate immunity in dogs 3 years after their second vaccination with a new multivalent, modified-live vaccine containing canine adenovirus type 2 (CAV-2), canine parvovirus (CPV), and canine distemper virus (CDV). Twenty-three seronegative pups were vaccinated at 7 and 11 weeks of age. Eighteen seronegative pups, randomized into groups of six dogs, served as challenge controls. Dogs were kept in strict isolation for 3 years following the vaccination and then challenged sequentially with virulent canine adenovirus type 1 (CAV-1), CPV, and CDV. For each viral challenge, a separate group of six control dogs was also challenged. Clinical signs of CAV-1, CPV, and CDV infections were prevented in 100% of vaccinated dogs, demonstrating that the multivalent, modified-live test vaccine provided protection against virulent CAV-1, CPV, and CDV challenge in dogs 7 weeks of age or older for a minimum of 3 years following second vaccination.     

Three-year rabies duration of immunity in dogs following vaccination with a core combination vaccine against canine distemper virus, canine adenovirus type-1, canine parvovirus, and rabies virus

Thirty-two seronegative pups were vaccinated at 8 weeks of age with modified-live canine distemper virus (CDV), canine adenovirus type-2 (CAV-2), and canine parvovirus (CPV) vaccine and at 12 weeks with a modified-live CDV, CAV-2, CPV, and killed rabies virus vaccine. An additional 31 seronegative pups served as age-matched, nonvaccinated controls. All test dogs were strictly isolated for 3 years after receiving the second vaccination and then were challenged with virulent rabies virus. Clinical signs of rabies were prevented in 28 (88%) of the 32 vaccinated dogs. In contrast, 97% (30 of 31) of the control dogs died of rabies infection. These study results indicated that no immunogenic interference occurred between the modified-live vaccine components and the killed rabies virus component. Furthermore, these results indicated that the rabies component in the test vaccine provided protection against virulent rabies challenge in dogs 12 weeks of age or older for a minimum of 3 years following vaccination.     

Evaluation of the efficacy and duration of immunity of a canine combination vaccine against virulent parvovirus, infectious canine hepatitis virus, and distemper virus experimental challenges

The results of this study confirmed that dogs vaccinated subcutaneously with a commercially available multivalent vaccine containing modified-live canine distemper virus, canine adenovirus type 2, canine parvovirus type 2b, and canine parainfluenza virus antigens were protected against sequential experimental challenge 55 to 57 months after initial vaccination given at 7 to 8 weeks of age. All 10 vaccinates were protected against clinical diseases and mortality following parvovirus and infectious canine hepatitis experimental infections. All vaccinates were protected against mortality and 90% against clinical disease following distemper challenge. These data support at least a 4-year duration of immunity for these three "core" fractions in the combination vaccine.     

Association between cancer chemotherapy and canine distemper virus, canine parvovirus, and rabies virus antibody titers in tumor-bearing dogs.

OBJECTIVE: To determine the association between cancer chemotherapy and serum canine distemper virus (CDV), canine parvovirus (CPV), and rabies virus antibody titers in tumor-bearing dogs. DESIGN: Prospective study. ANIMALS: 21 client-owned dogs with various malignancies and 16 client-owned dogs with lymphoma. PROCEDURE: In study A, serum antibody titers were measured by use of hemagglutination inhibition (CPV titers) or serum neutralization (CDV titers) before and at least 1 month after initiation of chemotherapy. Baseline values were compared with values obtained from a control population of 122 healthy dogs seen for routine revaccination. Titers were considered protective at > or = 1:96 for CDV and > or = 1:80 for CPV. In study B, serum IgG titers were measured by use of immunofluorescent assay (CDV and CPV titers) and rapid fluorescent focus inhibition test (RFFIT, rabies titers) at baseline and again at weeks 5, 8, and 24 of a standard chemotherapy protocol for treatment of lymphoma. An IgG titer of > or = 1:50 was considered protective for CPV and CDV. An RFFIT titer of > or = 0.5 U/ml was considered protective for rabies virus. RESULTS: Significant changes were not detected in CDV, CPV, and rabies virus titers following chemotherapy in tumor-bearing dogs. CONCLUSIONS AND CLINICAL RELEVANCE: Results suggest that established immunity to CDV, CPV, and rabies virus from previous vaccination is not significantly compromised by standard chemotherapy used to treat tumor-bearing dogs.     

Neutralizing antibodies against feline parvoviruses in nondomestic felids inoculated with commercial inactivated polyvalent vaccines

The virus neutralization (VN) antibody titers of serum samples from 18 individuals representing 8 carnivore species vaccinated with commercial polyvalent vaccines optimized for domestic cats containing inactivated feline panleukopenia virus (FPLV) were evaluated against canine parvovirus type 2 (CPV2). In addition, the titers among 5 individuals from 4 carnivore were evaluated against antigenic variants of feline parvoviruses; FPLV, CPV2, CPV2a, CPV2b, CPV2c, mink enteritis virus type 1 (MEV1) and MEV2. The polyvalent vaccines induced cross-reactive VN titers against antigenic variants of feline parvoviruses in nondomestic felids. However, we observed very low cross-reactive VN antibody in lions and Siberian tigers, therefore we should pay attention to CPV infections in these animals even if they were vaccinated with inactivated FPLV vaccines.     

Serologic evaluation of vaccinated American river otters

The Oklahoma Department of Wildlife Conservation acquired 20 American river otters (Lutra canadensis) between 1984 and 1985 for reintroduction into Oklahoma waterways. In 1985, 10 otters were evaluated for serum antibody titers after vaccination with canine distemper virus, canine adenovirus type 2, canine parvovirus (CPV), feline panleukopenia virus (FPV), feline rhinotracheitis virus (FRV), and feline calicivirus. Prevaccination serum-virus neutralization (SVN) antibody to feline rhinotracheitis virus was found in 2 otters and to feline calicivirus in 1 otter. Using an indirect fluorescent antibody (IFA) assay, prevaccination antibody to CPV and FPV was found in 2 otters. A significant increase in SVN antibody titers was found after vaccination of otters with canine adenovirus type 2 (6 of 8 animals) and feline calicivirus (1 of 8 animals). One of 8 otters developed significant antibody titers to CPV and FPV, as measured by IFA assay. Otters did not develop SVN antibody titers to canine distemper virus after vaccination. Antigens of feline leukemia virus, using ELISA, or antibodies to feline infectious peritonitis, using IFA assay, were not found in the 20 otters.     

Response of mink, skunk, red fox and raccoon to inoculation with mink virus enteritis, feline panleukopenia and canine parvovirus and prevalence of antibody to parvovirus in wild carnivores in Ontario.

Mink virus enteritis, feline panleukopenia and canine parvovirus-2 were inoculated separately into groups of raccoon, mink, red fox and striped skunk. Raccoons were highly susceptible to mink virus enteritis and feline panleukopenia, with animals developing clinical illness, and several dying within six to ten days of inoculation with lesions typical of parvovirus infection. Both viruses were shed in high titre in the feces of infected raccoons, and high antibody titres were stimulated. Raccoons inoculated with canine parvovirus-2 showed no signs; shedding of virus was sporadic though moderate titres of antibody developed. Mink inoculated with mink virus enteritis and feline panleukopenia developed signs and lesions of early parvovirus infection. No signs or significant lesions followed canine parvovirus-2 inoculation. Shedding of virus was heavy (mink virus enteritis) or sporadic (feline panleukopenia and canine parvovirus-2), though good serological responses were elicited to all three viruses. Red fox showed no signs of infection, shed all three viruses only sporadically, and the serological response was strong only to feline panleukopenia. Skunks developed low antibody titres, but no signs, and did not shed virus. Antibody to parvovirus was found in 79.2% of 144 wild red foxes; 22.3% of 112 wild raccoons; 1.3% of 157 wild skunks and 6/7 coyotes in southern Ontario. The likely significance of these viruses to wild and captive individuals and populations of these carnivores is discussed.     

Parvovirus-induced regression of canine transmissible venereal sarcoma

In 1981, during the worldwide canine parvovirus (PV) epizootic, canine transmissible venereal sarcomas growing in Beagles in a colony regressed earlier than expected after the dogs became infected with PV. Subsequent studies revealed that modified-live PV vaccine (feline panleukopenia virus) was capable of preventing tumor transplantation when the vaccine was inoculated simultaneously with the tumor in a site distant from the implantation site. However, the PV vaccine had no effect if it was inoculated 3 or 18 days after the tumor was transplanted.     

Duration of serologic response to three viral antigens in cats

OBJECTIVE: To determine whether vaccinated cats either remained seropositive or responded serologically to revaccination against 3 key viral antigens after extended periods since their last vaccination. DESIGN: Serologic survey. ANIMALS: 272 healthy client-owned cats. PROCEDURE: Cats were > or = 2 years old and vaccinated for feline panleukopenia virus (FPV), feline calicivirus (FCV), and feline herpesvirus (FHV). On day 0, cats were revaccinated with a vaccine from the same line of vaccines as they had historically received. Antibody titers were measured in sera collected on day 0 (prevaccination titer) and 5 to 7 days later (postvaccination titer). Cats were considered to have responded serologically if they had a day-0 hemagglutination inhibition titer to FPV > or = 1:40, serum neutralization (SN) titer to FCV > or = 1:32, SN titer to FHV > or = 1:16, or > or = 4-fold increase in antibody titer after revaccination. RESULTS: The percentage of cats that had titers at or above the threshold values or responded to revaccination with a > or = 4-fold increase in titer was 96.7% for FPV, 97.8% for FCV, and 88.2% for FHV. CONCLUSIONS AND CLINICAL RELEVANCE: In most cats, vaccination induced a response that lasted up to and beyond 48 months for all 3 antigens. Although not equivalent to challenge-of-immunity studies as a demonstration of efficacy, results suggest that revaccination with the vaccine used in our study provides adequate protection even when given less frequently than the traditional 1-year interval. The study provides valuable information for clinicians to determine appropriate revaccination intervals.     

Clinical and serological response of wild dogs (Lycaon pictus) to vaccination against canine distemper,canine parvovirus infection and rabies

Wild dogs Lycaon pictuis (n = 8) were vaccinated 4 times against canine distemper (n = 8) (initially with inactivated and subsequently with live attenuated strains of canine distemper) and canine parvovirus infection (n = 8) over a period of 360 days. Four of the wild dogs were also vaccinated 3 times against rabies using a live oral vaccine and 4 with an inactivated parenteral vaccine. Commercially-available canine distemper, canine parvovirus and parenteral rabies vaccines, intended for use in domestic dogs, were used. None of the vaccinated dogs showed any untoward clinical signs. The inactivated canine distemper vaccine did not result in seroconversion whereas the attenuated live vaccine resulted in seroconversion in all wild dogs. Presumably protective concentrations of antibodies to canine distemper virus were present in all wild dogs for at least 451 days. Canine parvovirus haemagglutination inhibition titres were present in all wild dogs prior to the administration of vaccine and protective concentrations persisted for at least 451 days. Vaccination against parvovirus infection resulted in a temporary increase in canine parvovirus haemagglutination inhibition titres in most dogs. Administration of both inactivated parenteral and live oral rabies vaccine initially resulted in seroconversion in 7 of 8 dogs. These titres, however, dropped to very low concentrations within 100 days. Booster administrations resulted in increased antibody concentrations in all dogs. It was concluded that the vaccines were safe to use in healthy subadult wild dogs and that a vaccination protocol in free-ranging wild dogs should at least incorporate booster vaccinations against rabies 3-6 months after the first inoculation.     

Clinical use of serum parvovirus and distemper virus antibody titers for determining revaccination strategies in healthy dogs

OBJECTIVE: To assess whether serum canine parvovirus (CPV) and canine distemper virus (CDV) antibody titers can be used to determine revaccination protocols in healthy dogs. DESIGN: Case series. ANIMALS: 1,441 dogs between 6 weeks and 17 years old. PROCEDURE: CPV and CDV antibody titers in serum samples submitted to a commercial diagnostic laboratory were measured by use of indirect fluorescent antibody (IFA) tests. On the basis of parallel measurements of CPV and CDV serum antibody titers in 61 paired serum samples determined by use of hemagglutination inhibition and serum neutralization methods, respectively, we considered titers > or = 1:5 (IFA test) indicative of an adequate antibody response. RESULTS: Age, breed, and sex were not significantly associated with adequate CPV- or CDV-specific antibody responses. Of 1,441 dogs, 1,370 (95.1%) had adequate and 71 (4.9%) had inadequate antibody responses to CPV, whereas 1,346 of 1,379 (97.6%) dogs had adequate and 33 (2.4%) had inadequate responses to CDV. Vaccination histories were available for 468 dogs (468 for CPV, 457 for CDV). Interval between last vaccination and antibody measurement was 1 to 2 years for the majority (281/468; 60.0%) of dogs and 2 to 7 years for 142 of 468 (30.3%) dogs. Interval was < 1 year in only 45 of 468 (9.6%) dogs. CONCLUSIONS AND CLINICAL RELEVANCE: The high prevalence of adequate antibody responses (CPV, 95.1%; CDV, 97.6%) in this large population of dogs suggests that annual revaccination against CPV and CDV may not be necessary.