ISRAEL JOURNAL OF
VETERINARY MEDICINE
A REVIEW OF CURRENT INTERNATIONAL
VACCINATION TRENDS FOR DOGS AND CATS. ARE WE
UP TO DATE AND IN-LINE WITH CONTEMPORARY
THINKING?
Vol. 59 (3) 2004 Trevor Waner
Veterinary Clinic, 9 Meginay Hagalil Street, 76200 Rehovot, Israel
Running title: Review of canine and feline vaccination trends
Address of corresponding author: Dr. Trevor Waner, B.V.Sc., Ph.D., Dipl
ECLAM 9 Meginay Hagalil Street, 76200 Rehovot, Israel.
e-mail: wanertnt@shani.net
Abstract
This review presents some highlights of current knowledge regarding the issue of annual
vaccination in dogs and cats and addresses whether there is a need for Israeli veterinarians to follow
international trends and to implement vaccination policies conforming to contemporary scientific
knowledge. An important driving force to reexamine existing veterinary annual vaccination protocols
was the serious concern regarding adverse effects caused by vaccination. The list of possible adverse
effects is presented and discussed. Methods concerning the manner in which persistence of immunity
after vaccination is measured are discussed. The results of two serological studies, in which the
protection of dogs and cats to major diseases preventable by vaccination are presented. The central
finding of both of these studies discussed here is that vaccination induces a serological response in
dogs and cats that lasts for extended periods of time. Published guidelines and recommendations for
both canine and feline vaccination schedules are reviewed. It was concluded that annual vaccination
may not be beneficial and in some cases may even be deleterious. The veterinarian is encouraged and
recommended to determine what is best for the individual patient and to tailor a vaccination program
for this purpose.
Historically, prophylaxis against important infectious diseases of dogs and cats has been
based on annual vaccination. This approach has resulted in excellent disease control for
infections that were once considered important causes of morbidity and mortality. Over the
past years veterinary medicine has seen advancements in vaccine technology making
vaccines more effective and safe. Furthermore evolution of scientific knowledge has resulted
in advances in the field of vaccinology. From the early 1990’s, professional as well as public
literature in Europe and the United States has been questioning whether annual vaccination is
necessary or even harmful. Based on a growing body of research and knowledge
veterinarians are required to judge whether there is a true need for annual vaccination (1-4).
This review presents some of the current knowledge available in the veterinary literature
regarding this concern, and addresses whether there is a need for Israeli veterinarians to
follow international trends and to implement vaccination policies conforming to contemporary
scientific knowledge.
Before dealing with current studies concerning with persistence of immunity after
vaccination, it is necessary to discuss which criteria are acceptable to determine whether
dogs and cats remain protected to specific agents after vaccination. Agreement about which
tests are reliable for assessing immune protection is pivotal for evaluating the validity and
relevance of the data derived from experiments. Essentially three methods are generally
accepted: Firstly, challenge studies are considered the “gold standard” for assessing
immunity (5). These studies are the most reliable but are impractical, very costly and time
consuming. The issue of whether challenge studies are ethical in pet dogs and cats has also
been raised (6). Challenge studies have been used especially to assess the efficacy of
vaccines like rabies.
A second technique to determine immunity or lack of immunity is based on serological
testing. High serum antibody titers have been shown to correlate reasonably with protective
immunity. For this reason researchers tend to define dogs with protective antibody titers as
those dogs with high titers, or at least titers higher than those documented to give protection
(6). Complicating the use of antibody levels to define protection is the that fact that although
CDV, CAV-2 and CPV antibodies correlate well with protection, the protective role of
antibodies against canine parainfluenza (CPIV) for example, is less clear-cut (7).
A third technique for establishing immunity is based on the anamnestic response. Beyond
the role of cytotoxic T-cells and circulating serum antibodies in the protection against
infectious diseases is the immune characteristic that depends on memory cells. Memory cells
of both T- and B- lineages are derived from naïve and effector lymphocytes (T- and B-cells)
during the immune process of the primary response. They differ from the effector cells by
escaping the process of apoptosis, which occurs in most living cells in the body. The
mechanism of this phenomenon is known at least for T-cells. The cytokine IL-15 seems to
contribute to enhancing immune memory by selectively propagating memory T-cells and by
blocking T-cell death mediated by IL-2 (8). As far as memory B-cells are concerned the
mechanism of longevity is still obscure. Hence, the crucial question that arises is for how long
can immune memory be maintained for cellular or humoral immunity (T- and B-responses,
respectively) without secondary exposure to a given antigen? In an attempt to elucidate this
issue, Demkowicz et al., examined the duration of T-cell memory in humans by performing in
vitro T-cell responses to vaccinia virus (9). (WHO recommended the cessation of
immunization against smallpox in the 1970’s). Vaccinia virus replicates in the cytoplasm of
infected cells and is not thought to persist or remain latent after the acute phase of infection.
Long-persisting vaccinia virus-specific memory cytotoxic T-cells where identified in adults who
had been immunized against smallpox as children for up to 50 years after immunization. In
another study regarding the duration of antiviral immunity following smallpox vaccination, it
was found that more than 90% of volunteers vaccinated 25-75 years previously still
maintained substantial humoral or cellular immunity (or both) against the vaccinia virus (10).
Antiviral antibody responses remained stable between 1-75 years after vaccination, whereas
antiviral T-cell responses declined slowly with a half-life of 8-15 years (10).
Hence, an animal that develops an immune response after vaccination possess immune
memory cells that will activate a rapid and effective serologic response to exposure even if
serum antibody titers have declined to low or undetectable levels.
Generally, the most effective protection against viral infections is gained by the Type-I
response (cellular immunity). However, as a result of the lack of an easy to perform, reliable
and relatively inexpensive technique, the level of immunization is expressed usually by titer of
serum antibodies, regardless of their relevance to the specific mechanism of immunity. Not
with standing, the anamnestic response has been used experimentally to gauge immunity in
dogs and cats where a response of a 4-fold or greater in post vaccination antibody titer versus
prevaccination is generally regarded as a positive serological response. Under these
circumstances it must be borne in mind that revaccination of seropositive animals may result
in little or no serologic response because preexisting antibodies may neutralize the vaccine.
A recent survey in the United Kingdom dealt with 147 pet dogs that had not been
vaccinated for at least three years, looking at persistence of immunity to three important
canine diseases preventable by vaccination, canine distemper (CDV), canine adenovirus
(CAV-2) and canine parvovirus (CPV) (6). Dogs examined for CPV serum antibodies found
that 95% of dogs surveyed were protected against CPV with the rest of the dogs having
borderline titers. In the case of CDV, 72% of dogs had protective titers, 18% borderline titers,
and 10% had low to undetectable serum antibody titers. For CAV-2 82% had protective titers,
14% borderline titers, and 12% low to undetectable titers. For all the antigens tested, the
incidence of low or borderline titers did not appear to increase with increasing time after the
last vaccination.
The authors defined the protective titers taking into account the variations inherent in the
biological systems used to assay antibodies. From their own experience and data from the
literature they chose to define a protective titer as that higher than generally accepted. In the
case of CPV natural boosting of the immune system was strongly suspected due to the high
proportion of dogs with protective antibodies and the fact that the virus is very stable in the
environment. Natural boosting was not considered to be factor in the case of CDV probably
due to environmental susceptibility of the virus. In the case of CAV-2 which is inactivated by
heat but resistant to many disinfectants and can survive for months in near freezing
conditions the authors raised the possibility of natural reinfection.
It was concluded that the chances of an adult dog that had received its primary
vaccinations being infected by CPV, CDV or CAV-2 were low mainly because the vaccines
trigger seroconversion in a large proportion of the dogs. They further emphasized that primary
vaccination remains essential. They were not able to determine the interval after vaccination
after which the dogs’ immunity would wane significantly. They suggested determining the
antibody titers in dogs and vaccinating only those dogs that are borderline or low.
Another recent study carried out in the United States set out to determine whether
vaccinated dogs and cats either remained seropositive or responded serologically to
revaccination for five key viral antigens in dogs and three antigens in cats after extended
periods since their last vaccinations (11, 7). The antigens tested in dogs were CDV, CPV,
CPIV and CAV-1 and - 2. In cats the three antigens tested were feline panleukopenia virus
(FPV), feline calicivirus (FCV) and feline herpesvirus (FHV). The dogs and cats in these
studies were client-owned animals maintained under domestic setting and assessed under
conditions encountered in everyday life. The study consisted of 322 dogs and 272 cats. The
dogs and cats were required to be clinically healthy, without any history of clinical disease to
the diseases tested and documented to have received their puppy/kitten vaccinations. The
cats were also required to have negative results to feline immunodeficiency virus and feline
leukemia virus. Furthermore dogs and cats were required not to be vaccinated for at least 12
months prior to the start of the study. Most of the dogs and cats participating in this study had
been vaccinated during the past two years and some had not been vaccinated for 3-4 years
and more. On enrollment into the study blood was collected from each animal and frozen after
separation. Immediately after blood sample collection the dogs and cats were vaccinated.
Five to seven days after vaccination each dog and cat was reexamined and a second blood
was drawn, separated and frozen. The 2 serum samples for each dog and cat were shipped
to a diagnostic laboratory for serologic testing.
Dogs and cats were considered to have responded serologically if they had antibodies to
one or more of the antigens before vaccination or had a 4-fold or greater increase in antibody
after revaccination. The percentage of dogs that had titers at or greater than the threshold
values or responded to revaccination with a • 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. The percentage of
cats that had titers at or greater than the threshold values or responded to revaccination with
a • 4-fold increase in titer was 96.7% for FPV, 97.8% for FCV and 88.2% for FHV.
The results of the feline serological study showed that the vast majority of cats were
protected for extended periods lasting in some instances 4 years or more following initial
vaccination. The conclusions of this study are similar to other studies also indicating that
immunological protection is long lasting following initial vaccination (12). Furthermore, in
another study by Lappin et al., it was concluded that regardless of vaccine type or
postvaccination interval, if detectable antibodies were identified against FPV, FCV, or FHV,
cats were protected against virulent challenge (13). An essential result of a number of studies
suggested that even low FPV, FCV and FHV serum antibody concentrations correlate with
protection (14).
Among the cats tested there were a small percentage of non-responders, that is, cats that
had no antibody titer on admission to the study or cats that did not have a postvaccination
anamnestic response. These non-responders constituted 3.7% FPC, 0.9% FCV and 5.7%
FHV of all the cats tested. Regarding these cats the authors suggested that annual
vaccination for a period of 2 years might be beneficial in young cats with an immune system
that may not be fully developed. For the majority of cats the authors concluded that their data
supported a 3-year vaccination interval regardless of the cats’ lifestyle associated risks.
The results of the dog study indicated that vaccination consistently induced a serologic
response for up to and beyond 48 months for all the 5 antigens tested. The authors concluded
that the results suggested a rationale for revaccination intervals of longer than 1 year for the
antigens tested. However, they pointed out that although CPIV antibodies lasted longer than
48 months after vaccination, the protective value of these circulating antibodies is in doubt as
clinical infection with CPIV is countered primarily by mucosal immunity and often involves
concurrent infections with agents like CAV-2 and Bordetella bronchiseptica. For CPIV the
authors recommended routine vaccination when necessary.
The persistence of immunity after vaccination and the necessity for booster vaccinations is
only one facet of concern when vaccinations are carried out on an annual basis. Another
concern regarding unnecessary vaccination is the possibility of post vaccination adverse
effects (15-17). A number of side effects to vaccination have been documented and are
reviewed below. Type I hypersensitivity or anaphylaxis is a well-characterized adverse event
associated with vaccination (15). In dogs clinical signs are reported most often in the skin,
gastrointestinal tract and less often in the respiratory tract. Fatalities due to anaphylaxis have
been reported. The clinical signs in cats with anaphylaxis show a different pattern than those
reported for dogs with the majority involving the gastrointestinal tract, less often the
respiratory tract and least often the skin. Fatalities have been reported in cats due to
anaphylaxis.
Type II hypersensitivity involving cell destruction mediated by antibodies may account of
the transient thrombocytopenia following vaccination (18, 19). There has been some concern
that vaccination may trigger autoimmune diseases (20-22). Reports of suspected autoimmune
hemolytic anemia in dogs developing within 2 to 14 days post vaccination has been reported.
Vaccine administration has also been hypothesized to a contributing factor for thryroiditis in
dogs (22). In pet dogs a significant increase in anti-canine thyroglobin antibodies has been
detected following vaccination, however whether these antibodies have a deleterious effect is
unclear (22). An experimental study evaluating the immune response to puppies routinely
vaccinated with commercially available distemper, adenovirus, leptospira, parainfluenza,
parvovirus plus coronavirus and rabies demonstrated the development of autoantibodies
particularly against fibronectin and laminin (15). The clinical significance of these
autoantibodies is not clear. Other side effects include immunosuppression (23, 24),
cutaneous vasculopathies resulting in alopecia (25), metaphyseal osteopathy (26, 27),
polyradiculoneutritis and encephalitis (1) and sarcoma in cats (28).
Annual vaccination has been placed in doubt based on a growing body of information
regarding the persistence of antibody after vaccination and the potential adverse effects
caused by frequent vaccination (16). Guidelines and recommendations have been published
for both canine and feline vaccination schedules (1-4).
The American Animal Hospital Association (AAHA) published in 2003 a report on canine
vaccine guidelines and recommendations (4). In this report the authors have made their
recommendations based on disease incidence and severity, vaccine efficacy and duration of
immunity, safely, and the health, welfare and lifestyle of the individual animals. For this
purpose they have divided vaccines into “core” (recommended vaccines) and “noncore”
(optional vaccines) and those generally not recommended vaccines. The authors stress that
vaccine decisions must be approached like any other medical decision, where indications and
contraindications must be taken into account and risk benefit concerns must be considered.
The AAHA report highly recommended for the CDV modified live vaccine (MLV) that
following the initial puppy vaccination schedule and the initial adult vaccination (>16 weeks of
age), a booster vaccination interval of 3 years, although they point out that vaccination is
protective for 5 to 7 years depending on the strain of CDV vaccine used. A similar
recommendation of a booster vaccination interval of 3 years is recommended for CPV (MLV),
CAV-2 (MLV) and CPIV (MLV or MLV topical). Vaccination for the various serovars of
Leptospira was recommended as optional. The AAHA report noted that the disease
prevalence of leptospirosis may vary for each serovar according to geographic location, and
therefore it was difficult to make an all-encompassing recommendation. They also reminded
the reader that post vaccination reactions in puppies and small breed dogs may be high, and
this should also be taken into account. They recommended annual vaccination or even biannual vaccination where dogs are exposed to significantly high risk.
Vaccination for Bordetella bronchispetica and Borrelia burgdorferi (Lyme borrelissis) was
graded as optional. Revaccination was recommended on the basis of risk and potential
exposure. Vaccination for canine coronavirus (killed or MLV), Giardia lamblia and CAV-1 was
not recommended by the AAHA report.
In January 2001 the "2000 Report of the American Association of Feline Practitioners and
Academy of Feline Medicine Advisory Panel on Feline Vaccine" was published
recommending the use of vaccines and the frequency of administration (2). Firstly the panel
discouraged the use of polyvalent vaccines except for those containing combinations of FPV,
FCV and FHV. This opinion was based on the idea that as the number of antigens in a
vaccine increases the probability of associated adverse reactions also increase. The panel
continued with a discussion on different feline vaccine components. Regarding FPV, the
panel noted that the immunity conferred by FPV vaccines was excellent and conferred
complete protection from infection and clinical disease for at least 7 years. They concluded
that following the initial series of vaccinations and revaccination 1 year later, cats should be
vaccinated no more frequently than once every 3 years. Similar conclusions were made for
FCV and FHV, recommending vaccination once every 3 years.
Routine vaccination against Chlamydia psittaci, feline infectious peritonitis, Bordetella
bronchiseptica and dermatophytosis infection was not recommended by the panel either due
to the frequency of adverse effects or due to still non-proven efficacy of the vaccines. The
routine use of Giardia lamblia vaccine was not recommended, however its use may be
considered in a comprehensive control program in environments in which expose to G.
lamblia is clinically significant. When parasite exposure is on-going revaccination at an annual
interval was recommended.
A publication by the American Veterinary Medical Association's (AVMA) "Council on
Biologic and Therapeutic Agents" in November 2002 reviewed both dog and cat vaccination
protocols (4). Besides dealing with the different vaccines available for dogs and cats, they
stressed the following principles: (i) Vaccination is an important part of preventive medical
practice. (ii) Vaccination is associated with benefits and risks and that knowledge of
immunology, vaccinology and pathobiology of infectious diseases is necessary for the
implementation of an effective individualized vaccination program. (iii) Revaccination should
be designed to create and maintain clinically relevant immunity while minimizing potential
adverse effects. The document pointed out that the historic practice of immunizing animals
annually is supported by minimal scientific data and that there is increasing evidence that
vaccines provide immunity beyond 1 year. Unnecessary stimulation of the immune system
may not result in enhanced disease control and may expose animals to unnecessary risks.
(iv) Veterinary practitioners should consider creating a “core” and “noncore” vaccination
program. Veterinarians and owners should carefully consider the benefits and risks of using
“noncore” vaccine products on an individual basis.
The AVMA publication goes on to list and discuss the recommendations for the vaccines
used in cats and dogs. For the “core” vaccines of dogs (CDV, CPV and CAV-2) (and cats
(FPV,FCV and FHV) the recommendations were similar to those of AAHA report. Although
the AMVA publication acknowledges that the revaccination interval can be extended beyond 1
year, they fail to recommend a specific interval or a range of intervals for either dog or cat
vaccination. The AVMA document differs from the AAHA recommendations regarding
vaccination for CPIV in dogs. Whereas the AAHA recommend vaccination of dogs every three
years following the initial puppy vaccinations, the AVMA recommends annual or more
frequent vaccination if this is deemed necessary.
In this review two major recent studies have been presented, each using a different but
complimentary serological approach for determining persistence of protection to important
canine and feline pathogens. It must be emphasized that although just two recent studies
have been quoted here, there is a great volume of literature on this subject dealing with
duration of protection to disease after vaccination in both dogs and cats (29-33). In the first
study the persistence of serum antibody was studied in dogs following a prolonged period
after the last vaccination (6). The second studies were set up to determine whether
vaccinated dogs and cats either remained seropositive or responded serologically to
revaccination after receiving their last vaccinations following extended periods of time (11, 7).
Whereas the first study assayed the serum antibodies present at the time of examination the
second study focused on serological response to revaccination, which is the immune-memory
cell response. Both methods are valid and both methods complement each other in
demonstrating the fact that the vast majority of dogs and cats remain protected from infection
after vaccination with potent and viable vaccines for a prolonged period extending in some
cases for a number of years.
With this knowledge it is proposed that vaccines should be administered using the same
principles that apply to any other pharmaceuticals. Vaccines should be administered
thoughtfully and appropriately. Where possible the response to vaccination should also be
monitored (34). The objective of companion animal vaccination is to protect the maximum
number of animals at risk and vaccinate no more frequently than necessary, bearing in mind
the risks of exposure and disease. Patient characteristics such as age, breed, immune status
and state of health may affect the risks and benefits of vaccination. Bearing this in mind
vaccination should be viewed as an individual procedure rather than a standard protocol
applicable to all animals (4).
The use of serological test kits may be a useful tool in assessing the immunological status
of dogs (12, 34). However the use of antibody titers to determine current immunity remains
contentious. There has been little standardization of methodology thus allowing for
inconsistent interpretation of whether an animal is immune or otherwise. The level of
protective antibody may vary from one test kit to another with doubtful correlation between
methodologies. Not withstanding, a number of ELISA kits have been developed and verified
for the detection of antibodies to a number of canine and feline infectious diseases. In many
cases the kits have been designed to show a positive reaction at a given cut-off point,
generally at or above the titer indicative of active or past infection. This same titer could also
be used to assess presence or absence of protective antibody in a healthy dog or cat. Among
the range of test kits available, the ELISA kit of Biogal (Kibbutz Galed, Israel) is the only test
kit that gives a semi-quantitative antibody titer result allowing the practitioner to judge the
level of antibody and therefore the degree of protection against a specific disease (35, 34).
Test kits such as these could not only be used to assess the antibody response of pups and
kittens after their initial vaccination, but also the persistence of serum antibody titers to
specific infectious diseases in adult dogs. The tests could be performed on an annual basis.
In this regard it should be borne in mind that a negative or low antibody titer might not
necessarily indicate lack of protection to a specific disease. These animals may still possess
rapid responding memory cells, which can be activated if the dog or cat became infected.
However looking at the results of the canine study of Bohm et al., it is highly likely that only a
small percentage of vaccinated dogs will lack antibody to the “core” canine diseases (6). On
the other hand, serum antibody tests are not available for all vaccinatable diseases. In this
case it is important to select a reliable laboratory with a quality control program sufficient to
make the test results reliable.
It is unanimously accepted that current vaccination programs in small animal practice have
played a crucial role in the prevention of devastating infectious diseases with an associated
decline in their morbidity and mortality (1-4). While the reduction in unnecessary vaccination
is desirable, veterinarians should keep in mind that outbreaks of previously controlled
endemic diseases might occur if the number of vaccinated animals in a given population falls
below a certain threshold. Furthermore it must be stressed that the effects of changing and
extending the vaccination interval on the canine and feline population immunity is largely
unknown. An example of an unfavorable outcome to decline in vaccination in humans is
pertussis, a respiratory disease (36). This disease is readily controlled by an efficacious
vaccine that resulted in the disease becoming rarer. In the course of time attention shifted
from disease prevention to possible adverse effects associated with vaccination, and resulted
in antivaccine movements in some countries. One study has shown that the incidence of
pertussis was lower by a factor of 10 to 100 in countries in which high vaccine coverage was
maintained compared to countries in which vaccination programs were compromised. On the
other hand the World Health Organization has decided to discontinue oral poliomyelitis
vaccination when no wild-type poliovirus transmission is detected in the world for 3
consecutive years. This type of decision can only be carried out using an efficient surveillance
program. Similar programs to evaluate the incidence of disease in pets do not exist, so
decisions based on this type of rationale are not applicable in small animal veterinary
medicine.
In conclusion, a growing body of literature is available indicating the current historic
approach of annual vaccination may not be beneficial and in some cases may even be
harmful. The veterinarian is encouraged and recommended to determine what is best for his
patient and to tailor a vaccination program for the individual. In this regard the discrimination
between “core” and “noncore” vaccines allow the veterinarian to assess the risks and
potential for infectious agents according to the age, breed, immune status, life style and
geographic location of the individual dog and cat, and vaccinate in accordance with the
veterinarian’s best judgment. This review has set out to give an overview of the current
thoughts on vaccination and in particular on annual vaccination. The question remains of how
to apply these principals both through the national professional veterinary organizations and
individual effort. Public awareness of these recommendations is also important in order to
make our decisions regarding vaccination frequency understandable to the lay public and
allow for debate and transparency.
LINKS TO OTHER ARTICLES IN THIS ISSUE
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