JAAHACanine Vaccination Guidelines

2022 AAHA Canine Vaccination Guidelines

John Ellis, DVM, PhD, DACVP, DACVM

†

, Elizabeth Marziani, DVM

†

Chumkee Aziz, DVM, DABVP (Shelter Medicine Practice), Catherine M. Brown, DVM, MSc, MPH,

Leah A. Cohn, DVM, PhD, DACVIM, Christopher Lea, DVM, DABVP (Canine and Feline Practice),

George E. Moore, DVM, PhD, DACVIM, DACVPM, Neha Taneja, MBA, MSHCM, LVT

ABSTRACT

These guidelines are an update and extension of previous AAHA peer-reviewed canine vaccination guidelines published in

2017. Vaccination is a cornerstone of canine preventive healthcare and one of the most cost-effective ways of maintaining

adog’s health, longevity, and quality of life. Canine vaccination also serves a public health function by forming a barrier

against several zoonotic diseases affecting dogs and humans. Canine vaccines are broadly categorized as containing

core and noncore immunizing antigens, with administration recommendations based on assessment of individual patient

risk factors. The guidelines include a comprehensive table listing canine core and noncore vaccines and a recommended

vaccination and revaccination schedule for each vaccine. The guidelines explain the relevance of different vaccine formu-

lations, including those containing modiﬁed-live virus, inactivated, and recombinant immunizing agents. Factors that

potentially affect vaccine efﬁcacy are addressed, including the patient’s prevaccination immune status and vaccine dura-

tion of immunity. Because animal shelters are one of the most challenging environments for prevention and control of

infectious diseases, the guidelines also provide recommendations for vaccination of dogs presented at or housed in ani-

mal shelters, including the appropriate response to an infectious disease outbreak in the shelter setting. The guidelines

explain how practitioners can interpret a patient’s serological status, including maternally derived antibody titers, as indi-

cators of immune status and suitability for vaccination. Other topics covered include factors associated with postvaccina-

tion adverse events, vaccine storage and handling to preserve product efﬁcacy, interpreting product labeling to ensure

proper vaccine use, and using client education and healthcare team training to raise awareness of the importance of vac-

cinations. (JAmAnimHospAssoc2022; 58:1–19. DOI 10.5326/JAAHA-MS-Canine Vaccination Guidelines)

AFFILIATIONS

University of Saskatchewan, Department of Veterinary Microbiology,

Saskatoon, Saskatchewan (J.E.); Hillside Animal Hospital, St. Louis, Missouri

(E.M.); Massachusetts Department of Public Health, Boston, Massachusetts

(C.M.B.); Association of Shelter Veterinarians, Houston, Texas (C.A.);

University of Missouri, Columbia, Missouri (L.A.C.); Auburn University,

Auburn, Alabama (C.L.); Purdue University, College of Veterinary Medicine,

West Lafayette, Indiana (G.E.M.); A Paw Partnership, Veterinary Well-being

Advocate, Centreville, Virginia (N.T.)

CONTRIBUTING REVIEWERS

Brett Sargent, DVM, DABVP (Front Range Veterinary Clinic, Lakewood,

Colorado); Jason Stull, VMD, MPVM, PhD, DACVPM (The Ohio State

University, College of Veterinary Medicine, Department of Veterinary Pre-

ventive Medicine, Columbus, Ohio)

Correspondence: john.ellis@usask.ca (J.E.)

† J. Ellis and E. Marziani were cochairs of the AAHA Canine Vaccina-

tion Guidelines Task Force.

These guidelines were prepared by a task force of experts convened by

the American Animal Hospital Association. This document is intended as

a guideline only, not an AAHA standard of care. These guidelines and rec-

ommendations should not be construed as dictating an exclusive

protocol, course of treatment, or procedure. Variations in practice may be

warranted based on the needs of the individual patient, resources, and

limitations unique to each individual practice setting. Evidence-based sup-

port for speciﬁc recommendations has been cited whenever possible and

appropriate. Other recommendations are based on practical clinical expe-

rience and a consensus of expert opinion. Further research is needed to

document some of these recommendations. Because each case is differ-

ent, veterinarians must base their decisions on the best available scientiﬁc

evidence in conjunction with their own knowledge and experience.

These guidelines are generously supported by Boehringer Ingelheim

Animal Health, Merck Animal Health, Zoetis Petcare, and Elanco Ani-

mal Health.

Bb (Bordetella bronchiseptica); CAV-1 (canine adenovirus type 1);

CAV-2 (canine adenovirus type 2); CDV (canine distemper virus); CFIA

(Canadian Food Inspection Agency); CIRD (canine infectious respiratory

disease); CIV (canine inﬂuenza virus); CPIV (canine parainﬂuenza virus);

CPV (canine parvovirus); CPV-2 (canine parvovirus type 2); DA2PP (dis-

temper, canine adenovirus type 2, parvovirus, parainﬂuenza combina-

tion vaccine); DOI (duration of immunity); ELISA (enzyme-linked

immunosorbent assay); HI (hemagglutination inhibition); IN (intranasal);

MDA (maternally derived antibodies); MLV (modiﬁed-live virus); VN (virus

neutralization); USDA (United States Department of Agriculture).

VETERINARY PRACTICE GUIDELINES

Introduction

Vaccination is an essential component of preventive pet healthcare

and an important pathway to nurturing a long-term veterinarian-

client-patient relationship. Universal, routine vaccination for high-

morbidity or high-mortality diseases such as canine distemper,

canine parvovirus enteritis, and rabies is necessary for individual

health and to maintain herd immunity to these infections, thereby

reducing the risk for disease spread and outbreaks. Recognizing that

there is hesitancy and skepticism in the human population to vacci-

nation, client education can play a key role in helping pet owners

understand that vaccination is a safe, effective, and necessary part of

their pet’s healthcare plan and that it acts as a barrier to zoonotic dis-

eases that can affect client households. All members of the veterinary

healthcare team should be able to communicate a consistent, uniﬁed

message to clients about the importance of immunization against

preventable infectious diseases. Protocols for baseline and individual-

ized vaccination plans are useful tools not only for implementing

vaccination practices but also for client education.

These guidelines include updated vaccination recommendations

and dosing schedules for canine vaccines licensed in the United

States. These recommendations are presented in easy-to-reference

tables, categorized by core and noncore vaccine antigens. Core vac-

cines are deﬁned as those recommended for all dogs irrespective of

lifestyle, e.g., rabies. Noncore vaccines are those recommended for

some dogs based on their risk of exposure when factors such as life-

style, geographic location, and endemic conditions are considered,

e.g., Lyme disease (Borrelia burgdorferi infection). Because animal

shelters represent one of the most challenging environments for the

prevention of canine infectious disease, these guidelines include a

detailed discussion of current recommendations for vaccination of

shelter dogs—at presentation, as resident animals, or in case of a dis-

ease outbreak. A simpliﬁed approach to determining the role of

patient serologic titers as indicators of the need for primary or repeat

vaccination is also described.

Licensed canine vaccines have a high degree of proven safety

and efﬁcacy. For this reason, dogs that present with an incomplete or

ambiguous vaccination or health history can still be vaccinated with

the expectation of a protective immune response and a low risk of

serious postvaccination adverse effects. Stated another way, veterinar-

ians can assume that the beneﬁts of vaccination far outweigh the

risks in cases of dogs with unknown immune status or vaccination

history—a common occurrence in veterinar y practice. Examples of

these real-world scenarios include the possibility of recent natural

exposure, absence of serologic data to guide a vaccination decision,

or suitability for noncore vaccines such as Leptospira spp. Thanks to

the reliability of the licensed vaccine armamentarium, a good rule of

thumb is, “When in doubt, vaccinate.”

Vaccine Overview and Types

Vaccines are one of the medical and public health successes of the

19th and 20th centuries. Their use has reduced morbidity and mor-

tality more than any other intervention in human and veterinary

medicine. Vaccination of companion animals protects the health of

the individual animal, improves animal welfare in community set-

tings (e.g., shelters), protects public health (e.g., rabies and leptospi-

rosis), and reduces the occurrence of infectious diseases that transmit

mainly within a species (e.g., canine variants of rabies virus, canine

distemper, and canine parvovirus). Vaccines have mitigated the

impact of infectious diseases on populations through herd immunity

so successfully that some dog owners may hold the perception that

vaccination is no longer necessary. Although individual dogs with

low-risk lifestyles (i.e., minimal exposure to other animals) may ben-

eﬁt from herd immunity, unvaccinated individuals are still more vul-

nerable to infection, and reductions in population-level vaccination

rates without eradication of the pathogen will inevitably result in a

recurrence of disease at outbreak levels. This has been clearly demon-

strated by recurrent canine distemper and parvovirus outbreaks in

shelters, and by recent outbreaks of measles in human populations

where reduced vaccine coverage exists.

Vaccine efﬁcacy, assessed during product development, is mea-

sured as the proportionate reduction of disease in vaccinated groups

compared with unvaccinated groups. Although necessary for the pur-

poses of licensing , vaccine efﬁcacy calculated under these controlled

settings may not equate to the population impact of the vaccine in

real-world settings. This impact, known as vaccine effectiv eness, is

more difﬁcult to quantify, especially in veterinary medicine, which

lacks the robust surveillance systems for monitoring the numbers of

individuals vaccinated and disease cases. Vaccination failures,

namely, the occurrence of disease in an animal that has received an

appropriately administered vaccine against that disease, are rare but

should be expected because no vaccine achieves 100% effectiveness.

Vaccination failures can occur for many reasons including:

 Failure of the vaccinated patient to mount an adequate immune

response.

 Exposure to the infection before being fully vaccinated.

 Interference of maternal antibodies.

 Improper storage or handling of the vaccine, including inappropri-

ate administration.

 Waning immunity (e.g., immunosenescence, or age-related deterio-

ration of the immune system).

 Vaccine manufacturing errors, such as lack of potency due to insta-

bility, expiration, or improper storage.

Vaccination failures should be promptly reported to the manu-

facturer. These reports are essential for detecting changes in product

performance due to def ects in particular lots of vaccine. In the

United States, if a veterinarian is unable to report to the

2 JAAHA | 58:5 Sep/Oct 2022

manufacturer, reports can be made directly to the United States

Department of Agriculture (USDA) Center for Veterinary Biologics.

More information and instructions on reporting are available online

from the USDA at https:// www.ap his.u sda.g ov/aph is/ou rfocus /

animalhealth/veterinary-biologics/adverse-event-reporting/ct_

vb_adverse_event.

Although no vaccine produces complete immunity or protec-

tion, the term duration of immunity (DOI) is commonly used for

the length of time a vaccine is expected to produce a robust immune

response and protection against illness following exposure. DOI data,

unlike vaccine efﬁcacy (the reduction in disease in vaccinated ani-

mals compared with unvaccinated animals) data, are not required

for licensure by the USDA. Exceptions to this include rabies vaccines

and, recently, new vaccines for which no pre-existing products are

available. Vaccine labels historically recommend booster doses every

year. Increasingly, data are available from postlicensing studies dem-

onstrating that the effect of many vaccines persists for extended peri-

ods. In some cases, DOI data have been submitted to the USDA to

update vaccine labels. These data have also been considered in vac-

cine guidelines developed by various stakeholder groups. Because

data also reveal differences in serologic titers following administra-

tion of different vaccine formulations for the same pathogen, extrap-

olation about efﬁcacy and DOI between products may not always be

appropriate.

1–11

Table 1 lists the characteristics of the four general categories of

canine vaccines based on the physical attributes of the vaccine

immunizing antigen.

Recommendations for Core and Noncore

Canine Vaccines

Based on existing data and Task Force expertise, the AAHA Canine

Vaccination Task Force has separated vaccines into two categories,

core and noncore. Core vaccines are those deﬁned by the Task Force

as vaccines recommended for all dogs irrespective of lifestyle, unless

there is a speciﬁc medical reason not to vaccinate. Examples of core

vaccines include canine distemper virus, canine adenovirus type 2,

canine parvovirus type 2, and rabies. Noncore vaccines are those rec-

ommended for some dogs based on lifestyle, geographic location,

and risk of exposure. Canine leptospirosis vaccine, canine Bordetella

vaccine, canine Lyme vaccine, canine inﬂuenza vaccine, and the

Western diamondback rattlesnake toxoid are considered noncore.

Table 2 lists core and noncore vaccines as determined by the

Task Force and their dosing recommendations. The designation of a

core vaccine was unanimously supported by all members of the Task

Force, but there was not always consensus regarding noncore vac-

cines. For example, some members of the Task Force asserted that

the canine leptospirosis vaccine should be considered a core vaccine

based on the increasing geographical prevalence of the disease. How-

ever, others preferred to leave this decision up to the veterinarian.

For regions where noncore pathogens are endemic, such as canine

leptospirosis and canine Lyme disease, these traditionally noncore

vaccines may be considered a core vaccine by veterinary practices in

those locations. As travel with pets becomes more popular and

vector-borne diseases spread, patients should be carefully assessed at

least annually to determine their vaccine requirements. These should

be considered general rather than universally prescriptive recom-

mendations. Veterinarians have the discretion to administer vaccines

off-label when scientiﬁc data, local circumstances, or evolving stand-

ards of care support that decision. In those situations, informed con-

sent from the client is still an important consideration.

These guidelines have been revised from prior versions to pro-

vide consolidated and updated clinical information, allowing the vet-

erinarian to select the best vaccines and protocols to ﬁt individual

patient needs. The guidelines are to be considered discretionary rec-

ommendations, and the Task Force emphasizes that practitioners

should be aware of the importance of reviewing and following manu-

facturer’s label instructions for speciﬁc vaccines, including instruc-

tions on proper mixing and use of diluents. Different types of

vaccines for the same pathogen may induce different immunologic

responses depending on vaccine technology, formulation, route of

administration, and patient factors.

Key Vaccination Considerations by Antigen

Canine Distemper Virus, Canine Adenovirus, and

Canine Parvovirus

Canine Distemper Virus (CDV)

Canine distemper virus can infect many species including domestic

dogs, wolves, coyotes, foxes, ferrets, skunks, and raccoons. Although

relatively unstable in the environment, the wide host range and

worldwide disease distribution allow for increased risk of virus expo-

sure for free-roaming dogs.

CDV vaccines are considered core vaccines, recommended for

all dogs regardless of geographical location. CDV vaccines contain

modiﬁed-live virus (MLV), high-titer, low-passage (less attenuated)

modiﬁed-live virus, or a (recombinant) canarypox vector with tar-

geted CDV genes. The minimum age to begin the primary vaccina-

tion protocol in puppies is 6–8 wk. MLV vaccines can be blocked,

however, by maternally derived antibodies (MDA) against CDV,

which decline exponentially over time and are usually absent by

12–14 wk of age. Revaccination is therefore recommended at 2 to

4 wk intervals until greater than 16 wk old; 18–20 wk of age may be

preferred particularly in areas of high CDV risk.

After the primary puppy series of vaccinations, a booster should

be administered within 1 yr. Thereafter, interval boosters every 3 yr

2022 AAHA Canine Vaccination Guidelines

JAAHA.ORG 3

are recommended; annual boosters are not necessary. Longer

(.3 yr) duration of immunity after vaccination has been suggested

butislargelyunsubstantiatedinthepeer-reviewedliterature.

Detection of CDV antibodies after vaccination can be performed

by hemagglutination inhibition (HI), virus neutralization (VN), or

enzyme-linked immunosorbent assay (ELISA). (See the guidelines

sectiononUtilizationandInterpretationofSerologicTiters).

Canine Parvovirus (CPV)

Canine parvovirus type 2 (CPV-2) is the most common cause of viral

enteritis in dogs. Three antigenic canine variants, CPV-2a, CPV-2b,

and CPV-2c, have been identiﬁed, but they are 99% genetically

similar.

Domestic and wild canids are susceptible to CPV-2, but risk of

infection is most likely from virus particles shed by other domestic

dogs. The virus is relatively stable in the environment. CPV is trans-

mitted by oronasal exposure, but CPV MLV vaccines are currently

registered for parenteral administration and are generally highly

effective once maternal antibody concentrations fall below inhibitory

levels.

CPV MLV vaccines are considered core vaccines, recom-

mended for all dogs regardless of geographical location, and are

TABLE 1

Categories of Canine Vaccines Based on Physical Type of Immunizing Antigen



A list of licensed veterinary biologics is available at www.aphis.usda.gov/aphis/ourfocus/animalhealth/veterinary-biologics/ct_vb_licensed_products.

4 JAAHA | 58:5 Sep/Oct 2022

TABLE 2

2022 AAHA Core and Noncore Vaccines for Dogs



IN, intranasal; SQ, subcutaneous.



For dogs in shelter environments, see narrative for additional recommendations.

2022 AAHA Canine Vaccination Guidelines

JAAHA.ORG 5

currently considered protective against the three known variants.

The minimum age to begin the primary vaccination protocol in pup-

pies is 6–8 wk. However, MLV vaccines can be blocked by MDA

against CPV, which decline exponentially over time and may persist

for 13 –15 wk or possibly longer.

2,14

Revaccination is therefore

recommended at 2 to 4 wk intervals until greater than 16 wk old;

18–20 wk old is preferred particularly in areas of high CPV risk.

In spite of the core vaccination recommendation for CPV, CPV

diagnoses in young dogs (,1 yr old) continue owing to a lack of

protective antibodies, particularly in dogs presenting to animal shel-

ters.

Although host-related factors may play a role, failure to com-

plete primary vaccine schedules or vaccine storage or administration

errors may account for many or most “vaccine failures.”

16,17

After the primary puppy series of vaccinations, a booster should

be administered within 1 yr. Thereafter, interval boosters every 3 yr

are recommended; annual boosters are not necessary. Longer

(.3 yr) duration of immunity after vaccination has been suggested

butislargelyunsubstantiatedinthepeer-reviewedliterature.

Detection of CPV antibodies after vaccination can be performed

by HI, VN, or ELISA diagnostic tests. (See section on Utilization and

Interpretation of Serologic Titers.)

Canine Adenovirus (CAV)

Canine adenovirus type 2 (CAV-2) is considered a core vaccine, pri-

marily because it is necessary for the prevention of canine adenovirus

type 1 (CAV-1) (against which it cross-protects),

the cause of infec-

tious canine hepatitis, historically recognized as a severe and often

fatal disease of canids. Although uncommon, sporadic cases of CAV-

1 infection are still reported.

Vaccination schedules for parenteral

CAV-2 vaccines follow the recommendations for CDV and CPV,

and CAV-2 is usually a component of combination vaccines.

CAV-2 can also cause tracheobronchitis and is part of the canine

infectious respiratory disease (CIRD) complex. Given in combination

with canine parainﬂuenza virus (CPIV) and Bordetella vaccines, MLV

CAV-2 vaccine can be administered intranasally (IN) to puppies as

young as 3 wk of age, as mucosal immunity is not blocked by MDA.

Rabies

In the United States, stray dog control programs initiated in the

1940s, combined with routine rabies vaccination of owned dogs,

eliminated the canine rabies virus variant (strain) from circulation by

2008. The elimination of this variant of an almost uniformly fatal

virus from a domestic animal species that lives as a companion in

close contact with humans has saved both canine and human lives.

Today, in the United States and Canada, dogs (and humans) remain

at risk from host-adapted rabies virus variants in wildlife reservoir

species such as skunks, raccoons, foxes, and bats. The extent of spill-

over from wildlife is driven by the wildlife reservoir in the endemic

area, with spillover most common in areas with the raccoon variant,

somewhat less with skunk variants, and least common in areas where

only bat variants occur. The US CDC publish an annual rabies sur-

veillance summary that includes useful maps illustrating the distribu-

tion of terrestrial rabies virus variants as well as spillover events into

dogs. Links to recent publications on rabies and rabies epidemiology

are available at https://www.cdc.gov/rabies/resources/publications/

index.html. The Canadian Food Insp ection Agency (CFIA) also

compiles rabies statistics at https://inspection.canada.ca/animal-

health/terrestrial-animals/diseases/reportable/ra bies/rabies-in-

canada/eng/1356156989919/1356157139999.

Because of the high fatality rate and public health risk posed by

rabies infection, administration of rabies vaccine to dogs is legally

mandated in many jurisdictions. Age at initial vaccination, timing of

booster doses, vaccine formulation, response to overdue booster

doses, and whether rabies vaccine exemptions are permitted may all

be stipulated in laws or regulations. Mandates can exist at the local,

state, and provincial levels, and veterinarians should be aware of all

applicable requirements in their area. Veterinarians that serve clients

in multiple jurisdictions with variable requirements should generally

apply the requirements of the jurisdiction where the animal resides.

Local and state health departments (https://www.cdc.gov/rabies/

resources/cont acts. html) and state public health veterinarians (listed

at http://nasphv.or g/Documents/S tatePublicHealthV eterinariansB y

State.pdf) are important sources of information about vaccine

requirements, local rabies epidemiology, animal rabies testing, and

risk assessments following a possible rabies exposure.

Rabies vaccines are highly immunogenic and effective. Vaccine

failures are rarely reported. In jurisdictions where it is not man-

dated, rabies is recommended as a core vaccine, used in accordance

with the most current recommendations in the Compendium of

Animal Rabies Prevention and Control (http://www.nasphv.org/

documentsCompendia.html). Currently, all licensed rabies vaccines

for dogs are inactivated (killed) with 1 and 3 yr DOI formulations

available. All licensed products are labeled for puppies 3 mo of age

and older. A booster dose is recommended 1 yr following the initial

vaccination regardless of the formulation or age at initial vaccina-

tion. The booster’s purpose is to immunize any animals that failed

to respond to the initial dose. At this time, there are no published

data supporting the efﬁcacy of half-doses of rabies vaccine.

Legal exemptions from rabies vaccination requirements are

only available in certain jurisdictions. Because exposure to rabies

poses a risk to both animal and human health in unvaccinated or

undervaccinated dogs, possible exemptions should be discussed with

the owner in the context of the animal’s health and lifestyle (i.e., risk

6 JAAHA | 58:5 Sep/Oct 2022

of exposure). Veterinarians should document these discussions in

the medical record. Antibody titer levels as correlates of protection

have not been established for rabies, and serologic testing is not con-

sidered a substitute for vaccination.

20–25

Leptospirosis

Vaccination for the prevention of leptospirosis should be strongly

considered for most dogs in North America as the disease can be

life-threatening, is endemic in much of the continent, and is zoo-

notic. In addition to protection from disease, vaccination may be

necessary to meet state or international requirements for importation

and transport of dogs.

Leptospirosis is a bacterial infection caused by spirochetes in

the genus Leptospira, including L interrogans and Lkirschneri.Sur-

face antigens delineate multiple different serovars, with the predomi-

nant disease-associated serovars varying with geographic location

and over time. In the past, L interrogans serovars Canicola and Icter-

ohemorrhagiae were predominant in North American dogs, and vac-

cines for these serovars have been available since the 1960s.

more recent years, L interrogans serovars Pomona, Bratislava, and

Autumnalis and L kirschneri serovar Grippotyphosa have emerged as

important canine pathogens.

Quadrivalent vaccines for use in

North America now include the addition of serovars Pomona and

Grippotyphosa bacterins. The Task Force recommends the use of the

4-serovar vaccines for protection against the most relevant pathogens

because vaccines induce only partial or no immunity to heterologous

serogroups.

28,29

Most leptospiral vaccines are adjuvanted, killed whole-cell bac-

terins, but nonadjuvanted bacterin vaccines have been marketed

more recently.

28,30

As is typical for bacterin vaccines, annual boosters

are required, with DOI shown for various vaccine serovars ranging

from 12 to 18 mo.

30–35

Most dogs in North America should be considered at risk of

leptospirosis. Historically, the disease was most common in large-

breed dogs with rural outdoor exposure. This is no longer true.

Small-breed dogs are frequently infected, perhaps because of urban

and suburban exposure of dogs to wildlife reservoirs including

rodents.

36,37

Dogs of any age, breed, or sex can be infected.

Lepto-

spirosis occurs throughout North America, and while often associ-

ated with exposure to water, infection is well documented in arid

regionssuchasArizona.

Risk factors for leptospirosis include dogs

spending any time outdoors (including urban, suburban, and rural

environments), exposure to rodents, and time in kennels or dog

daycares.

37–39

Vaccination against leptospirosis can induce antibodies that

may lead to false-positive serologic tests meant for disease diagnosis.

Both microscopic agglutination tests and point-of-care serologic

assays are impacted by this effect.

40–45

Fortunately, this becomes less

important in light of the fact that clinical disease is unlikely in vacci-

nated dogs. Vaccination does not result in positive real-time poly-

merase chain reaction test results.

Leptospirosis is an important zoonotic pathogen.

Although

there is little evidence of direct human infection from dogs,

greater canine ex posure to contaminated environments a nd close

contact with people may link environmental sources to

humans.

47–49

Newer vaccines have been documente d to dramati-

cally reduce or p revent renal carriage and urina ry sh edding of

leptospires from exposed dogs, potentially pro tectin g hu mans

even if indirectly.

27,32,35,50,51

Historically, veterinarians have been concerned about adverse

reactions to leptospiral vaccines.

52–54

Vaccineformulationshavenow

been altered to minimize the likelihood of such reactions. Based on

available information, adverse reactions to leptospiral vaccines seem

to be rare, with ,53 adverse events per 10,000 doses.

53,54

Most

adverse reactions are minor, and serious anaphylactic reactions were

reported no more often for dogs given leptospiral vaccines than for

other vaccine antigens. Nevert heless, adverse reactions of any type

are more likely in smaller and younger dogs.

For this reason, the

Task Force suggests that the initial dose be administered at or after

12 wk of age. Other measures to mitigate adverse reactions include

minimizing the number of different vaccines administered at a single

visit and following manufacturers recommendations, such as allow-

ing a vaccine to reach room temperature before injection.

Borrelia (Lyme Disease)

Vaccination for Lyme borreliosis should be considered for dogs that

live within or travel to regions with emerging or endemic Lyme dis-

ease. Lyme disease is caused by infection with tick-transmitted borre-

lial pathogens. Although at least 21 species of borrelial pathogens can

cause Lyme disease, in North America disease is due almost exclu-

sively to Borrelia burgdorferi.

55,56

In 2014, species in the B burgdorferi

sensu lato complex were awarded a new genus designation, Borre-

liella. However, this nomenclature is not yet routinely used by veteri-

narians and Bburgdorferirefers to either.

Lyme disease is transmitted by the bite of Ixodid ticks.

In the

northeastern, mid-Atlantic, and north-central United States and east-

ern Canadian provinces, the primary vector is Ixodes scapularis

(black-legged tick, or deer tick), whereas on the Paciﬁccoast,thepri-

mary vector is Ixodes paciﬁcus (western black-legged tick). Although

the geographic expansion of endemic areas may well occur, currently

infections are largely restricted to clusters of states where these ticks,

and appropriate mammalian disease hosts, are abundant.

2022 AAHA Canine Vaccination Guidelines

JAAHA.ORG 7

Dogs that spend time outdoors in endemic regions are most

likely to beneﬁt from vaccination. Vaccination should be comple-

mented with an ectoparasite control program as prevention of tick

feeding prevents dis ease transmission.

57,58

For dogs with travel

planned to an endemic area, both initial vaccinations should be com-

pleted 2 to 4 wk before travel. In a recent large dataset (2013–2019),

states with $5% seroprevalence in tested dogs included (in order of

highest to lowest prevalence) Connecticut (15.5% seroprevalence),

Massachusetts, Vermont, Maine, Pennsylvania, New Hampshire,

Rhode Island, New York, New Jersey, West Virginia, Minnesota, Vir-

ginia, Maryland, Delaware, Wisconsin, and District of Columbia.

In Canada, the disease is endemic in portions of Manitoba, eastern

Ontario, southern Quebec, Nova Scotia, and New Brunswick.

60,61

Dogs can serve as sentinels for infection in humans for this zoonotic

disease, and regions with the greatest canine seroprevalence mirror

regions with more human infections.

59,62

Fortunately, although

Lyme disease is zoonotic, there is no direct transmission from

infected dogs to people, and infection in either species depends on

vector transmission.

Most dogs infected with Bburgdorferiremain healthy.

Only

#10% develop a polyarthritis that is responsive to antimicrobial

therapy.

The most important potential consequence of infection is

protein-losing nephropathy. For the estimated 1 to 5% of infected

dogs that develop Lyme nephritis, the outcome is often fatal despite

antimicrobial therapy.

63–65

Predisposition to Lyme nephritis has

been suggested for retriever breeds, perhaps warranting additional

consideration for vaccination in these breeds.

63,64,66

There are four types of Borrelia vaccines approved for use, each

of which has been proved safe and efﬁcacious. Vaccines for preven-

tion of Lyme disease exert their protective effect in an unusual way.

All available vaccines can induce canine antibodies that bind borre-

lial outer surface proteins that are expressed while the pathogen is in

the tick (OspA). Having only OspA in a vaccine has been shown to

be effective.

It is also known that lipidation is a determinant of

immunogenicity, and the lipidated recombinant OspA-only vaccine

elicits a robust immune response.

Some vaccines can also induce

antibodies to an antigen that is expressed shortly after transmission

to the dog (OspC).

56,69,70

When the tick ingests antibodies to OspA

from the vaccinated dog while feeding, the bacteria are killed before

transmission. Antibodies to OspC extend protection against any bac-

teria that were not successfully killed inside the tick, thus acting syn-

ergistically with antibodies to OspA.

69,70

Antibodies induced through vaccination may or may not result

in positive serologic tests depending on test methodology.

63,71–73

It is

important to understand the impact of vaccination on tests used for

either screening or disease diagnosis. Differentiation of vaccination

from infection is possible for Bburgdorferi.

Bordetella, Canine Parainfluenza, and

Canine Influenza

Previously evaluated

challenge of immunity studies in Bordetella

bronchiseptica (Bb)-seronegative beagle puppies have provided vari-

ably convincing evidence of the efﬁcacy of inactivated injectable,

modiﬁed-live combination IN and single-component oral vaccines

for Bb. More recently, current combination IN and single-component

oral vaccines for Bb have been directly compared.

75,76

Data from

these studies

75,76

are conﬂicting concerning the equivalency of the

oral versus IN route in conferring immunity; one showed no differ-

ence between routes,

whereas the other demonstrated superior clini-

cal efﬁcacy of the IN route.

Altogether, available data indicate that

commercial vaccines for Bb all “work” at some level, regardless of the

route of administration.

74–76

However, in general, the IN (versus oral)

route of administr a tion is prefera ble for respira tory pathogens. This is

because it has been recognized that the common mucosal immune

system, as originally conceptualized, was an oversimpliﬁcation and

that there is compartmentalization of mucosal immune responses, at

least to some extent, making IN delivery of antigen more effective

than oral at stimulating responses in the respiratory tract.

77–83

There may be an immunological beneﬁt in combining different

vaccines and routes of administration in a primary series. This strat-

egy is called “heterologous prime-boost” and involves administering

different forms of an antigen by different routes to broaden and

extend a response.

Although little studied in small animal veteri-

nary medicine, there is an extensive comparative literature,

includ-

ing a dog-relevant Bordetella pertussis murine model,

supporting

this approach. Currently, heterologous prime-boost is being widely

investigated in an effort to improve responses to vaccines for

COVID-19.

One study using a combination of IN and injectable

(whole-cell bacterin) Bb vaccines demonstrated a signiﬁcant clinical

beneﬁt to this approach versus either vaccine alone.

However, this

strategy has not yet been evaluated with current canine vaccines for

Bb or other pathogens.

Concerning boosting of Bb vaccines, current combination IN

and single-component acellular injectable Bb vaccines have been

shown to induce equivalent anamnestic (memory) Bb-speciﬁcIgG

andIgAresponseswhenusedasboostervaccinesinpreviously

immunized adult household dogs.

There are no similar published

studies concerning the use of the single-component oral vaccine for

this purpose or any use in household dogs.

Dogs that are at risk for Bb are also at risk for canine parain-

ﬂuenza virus (CPIV) and canine adenovirus virus-2 (CAV-2) and

should be vaccinated for all three pathogens.

88,89

Only the current

combination IN and injectable (core) vaccines contain these patho-

gens. Therefore, the use of single-component oral and injectable Bb

vaccines is not recommended. Exceptions include dogs that cannot

8 JAAHA | 58:5 Sep/Oct 2022

be vaccinated IN, or in the case where the injectable Bb vaccine is

used simultaneously with the injectable core vaccines as a booster for

IN primed responses in a puppy series.

85,86

If an IN (modiﬁed-live)

Bb vaccine is inadvertently administered by injection, the vaccine

package insert or manufacturer should be consulted, as resulting

inﬂammatory reactions can be serious.

Duration of immunity and related recommendations for annual

vaccination for Bb and CPIV are largely based on experimental infec-

tions in seronegative laboratory beagle puppies.

74,91,92

Such studies,

usually conducted at peak immune response after vaccination, can

generally accurately assess the ability of a vaccine to reduce disease.

However, the validity of using such studies employing group-housed,

genetically similar subjects to determine DOI conferred by vaccines to

household dogs is questionable. It is difﬁcult to model heterogeneous

household conditions comprising the plethora of the host, environ-

mental and pathogen cofactors that can contribute to the brevity or

longevity of protective clinical immunity. The latter endeavor requires

well-designed and well-conducted ﬁeld trials, including disease report-

ing; however, these types of studies are rare. One seminal study of the

natural history of Bb indicated that the duration of clinical immunity

(reduction of disease) may be as short as 6mo.

The duration of

clinical immunity to CPIV in household dogs is unknown.

There-

fore, for patients at high risk for CPIV and Bb, it may be advantageous

to use IN combination Bb and CPIV vaccines more frequently than

annually, for example, before boarding. In addition to boosting adap-

tive immune responses, the latter practice may better ameliorate dis-

ease through stimulation of the local innate immune response (type 1

interferon),

although this is poorly documented in small animals.

Canine inﬂuenza virus (CIV) serotypes H3N8 and H3N2 have

been documented in North America and other parts of the world.

Disease caused by these viruses is usually indistinguishable from that

caused by other respiratory pathogens associated with canine infec-

tious respiratory disease (CIRD), although severe and sometimes

fatal disease can occur in CIV-infected dogs. In contrast to CPIV,

which tends to be endemic, or at least prevalent, in canine popula-

tions,

88,89

CIV infections and clinical disease to date have occurred

as multicentric nonsustaining outbreaks.

Therefore, the routine use

of CIV vaccines in all dogs is currently not recommended. Etiologic

diagnoses of CIRD cases using quantitative polymerase chain reac-

tion respiratory pathogen panels, together with monitoring of the

current circulation of CIV (https://www.vet.cornell.edu/animal-

health-diagnostic-center/news/canine-inﬂuenza-civ-updates), should

be used to determine whether CIV vaccination is warranted in indi-

vidual dogs, especially in dogs that are boarded and otherwise com-

mingled at dog daycare, dog parks, dog shows and agility events, and

in dogs who travel. Although immunity to inﬂuenza viruses is pri-

marily serotype-speciﬁc, the use of bivalent CIV vaccines may avoid

skewing of responses to one serotype.

This could broaden protec-

tive immunity and is therefore recommended.

Rattlesnake Toxoid

Currently, there are no published data documenting the efﬁcacy of

the western diamondback rattlesnake (Crotalus atrox)venomtoxoid

in dogs.

97–99

In a published experimental challenge study,

100

mice

were vaccinated with 50- to 1500-fold (by volume) higher doses of

toxoid than recommended in dogs and were subsequently challenged

intraperitoneally with high doses (twice the LD

)ofvenom.This

protocol and challenge are of questionable relevance to rattlesnake-

bitten dogs. In addition, although vaccinated mice had an increased

survival time, a cohort of vaccinees died or required euthanasia

earlier than unvaccinated controls following exposure to venom.

Similarly, adverse reactions, including anaphylaxis, in previously vac-

cinated, then envenomated, dogs have been reported.

The venom of pit vipers including the Crotalidae is antigenically

heterogeneous.

101

Despite the manufacturer’sclaimsofcross-

protection against envenomation by pit vipers other than Catrox,

there are no published data to support this in dogs. Veterinarians

choosing to use this toxoid should be aware of the lack of peer-

reviewed published data. Polyvalent antivenin therapy is an alterna-

tive to vaccination in suspect cases of rattlesnake bite.

Vaccination of Shelter Dogs and Puppies

Increased opportunities for disease exposure and transmission,

heightened animal stress, and high population turnover rates con-

tribute to an elevated risk for infectious disease in dogs housed in

high-density environments such as animal shelters. In addition, dogs

entering shelters are less likely to be immune against CPV and CDV

than owned dogs.

102–104

Of equal importance, infectious diseases are

detrimental for individual animals, entire shelter populations, and

community animals if an outbreak occurs. These increased environ-

mental and patient risk factors inherent to shelter populations war-

rant more stringent vaccination requirements than those for owned

dogs. Accordingly, all dogs, unless severely ill and unable to be

housed within the shelter, should be vaccinated upon shelter entry.

MLV vaccines should be used (as opposed to inactivated vaccines)

owing to the possibility of more rapid onset of immunity. The

DA2PP vaccination schedule in puppies should be started at a youn-

ger age, have shorter intervals between vaccinations, and end at an

older age than that in owned puppies.

Core vaccines for dogs in shelter environments include paren-

teral MLV DA2PP, IN Bb and CPIV, and parenteral rabies. Addi-

tional high-density or high-risk environments, including foster

homes, foster-based rescues, breeding facilities, sanctuaries, boarding

2022 AAHA Canine Vaccination Guidelines

JAAHA.ORG 9

kennels, and pet stores, should consider following the same vaccina-

tion protocol.

Unless sufﬁcient and reliable documentation of current vaccina-

tion status is presented, all dogs and puppies 4 wk of age and older

should receive an MLV DA2PP vaccine at or before shelter entry

and receive boosters at 2 to 3 wk intervals until they reach 18–20 wk

of age. In addition, exposure to infectious disease should be physi-

cally avoided for puppies, ideally through placement in foster care

until adoption or upon reaching 18–20 wk of age.

All dogs older than 18–20wkofageattimeofentryshould

receive an initial dose of MLV DA2PP vaccine followed by a booster

vaccine 2–3 wk later, administered either within the shelter, if the dog

remains in care, or by their owner’s veterinarian after adoption.

When dogs are housed in shelters for prolonged periods of time, they

should receive booster vaccinations as recommended for owned dogs.

All puppies and dogs older than 3 wk of age should receive an

IN Bb and CPIV vaccine with or without CAV-2 at or before entry

to mitigate CIRD. Although not documented in dogs, IN administra-

tion probably stimulates a local, rapid innate (interferon) response in

addition to mucosal IgA. In puppies, this immune response avoids

interference from maternal antibodies.

89,105,106

Single-component

mucosal vaccines that contain only Bb should be avoided because

dogs that are deemed at risk for Bb should be vaccinated against

CPIV as well. Injectable Bb vaccines should be avoided in shelter

environments owing to a delayed onset of immunity, including little

stimulation of the local immune responses in the upper respiratory

tract. This leads to reduced efﬁcacy in limiting CIRD compared with

IN vaccines. Oral or injectable single-component Bb vaccines are

only recommended when it is not possible to administer a two-way

IN vaccine.

A single dose of a rabies vaccine should be administered paren-

terally to all dogs older than 12 wk of age before release from the

shelter. Rabies vaccination is not required upon shelter entry, as risk

of exposure to rabies within the shelter environment is limited. How-

ever, if a long-term stay is anticipated, rabies vaccine should be

administered on entry with the other core vaccines. Local legal man-

dates regarding the level of veterinary supervision required for rabies

vaccination should be considered when developing shelter protocols.

Rabies vaccination is acceptable even if additional vaccines may have

been administered to the patient within the past 2 wk. Conclusive

evidence is lacking that concurrent vaccination against multiple

pathogens will impair the expected immune response to any individ-

ual component. Ensuring shelter dogs are vaccinated against rabies

upon release from the shelter provides a signiﬁcant public health

beneﬁt and outweighs any theoretical risk of vaccine interference.

Routine vaccination of shelter-housed dogs against Leptospira,

B burgdorferi (Lyme disease), and canine inﬂuenza virus (CIV;

H3N8 or H3N2 serotypes) is not recommended because these infec-

tions usually pose a minimal risk within the shelter environment.

However, local endemic or epizootic infections, such as in CIV out-

breaks with potential for shelter exposure, as well as available shelter

resources, legal require ments, and the risks and beneﬁts of vaccines

should be considered if adopting these noncore vaccinations in a

shelter protocol.

107

Shelters should advise owners to discuss an indi-

vidually tailored vaccination program with their veterinarian after

adoption.

Pregnancy and mild illness or injury are not contraindications

to administering core vaccines (CDV, CPV, CAV-2) to shelter-

housed dogs. The overall beneﬁts of MLV vaccination in a high-risk

environment outweigh the potential risks posed by vaccination.

108

adogismildlyillwhenvaccinatedonentrytotheshelterandthe

immune response to vaccination is of concern, then boostering the

MLV DA2PP vaccine in 2–3 wk (or after the animal has recovered)

will likely provide additional protection. Shelters that vaccinate all

animals on entry provide optimum herd immunity within their pop-

ulation. Conversely, shelters that do not vaccinate on entry or do not

vaccinate all dogs are at higher risk for an infectious disease

outbreak.

109,110

Infectious Disease Outbreak Management in Shelters

An infectious disease outbreak is one of the more daunting chal-

lenges in the high-risk animal shelter setting. Temporary cessation of

animal intakes is a helpful initial approach to an outbreak. Appropri-

ate vaccination of resident or incoming dogs is a crucial strategy

when an infectious disease outbreak occurs in the animal shelter

population. A proper vaccination strategy in the face of an outbreak

is dependent on the pathogen involved, its route of transmission

(oral vs. respiratory), the stage of the outbreak, effectiveness of local

sanitation practices, and the vaccine formulations being used. Unfor-

tunately, there are virtually no published data from controlled studies

in dogs that address these issues, relegating decisions to clinical

judgments.

Serological testing offers shelters an effective tool to help man-

age disease outbreaks, particularly in the case of CDV and CPV, as

opposed to depopulation or prolonged lockdown of the shelter.

Although additional host, pathogen, and environmental cofactors

that contribute to disease outbreaks must also be taken into account

during the outbreak management process, serological testing can

provide supplemental insights. Serological testing, by providing indi-

vidual risk assessment, can assist in population ﬂow decision making

during an outbreak. In general, healthy, seropositive dogs, especially

those with high titers, are likely resistant to disease and can be con-

sidered low risk. They can be adopted with appropriate waivers.

10 JAAHA | 58:5 Sep/Oct 2022

Healthy, seronegative dogs, who are potentially susceptible to disease

andconsideredhighrisk,shouldbequarantinedandseparatedfrom

the rest of the population (ideally, placed in foster care outside of the

shelter). They should be revaccinated, observed for development of

clinical signs throughout the anticipated incubation period of the dis-

ease, and serologically retested 10–14 days later. Puppies, especially

those #4 mo of age, require additional management during an out-

break. Serological testing and risk assessment of dogs in this age

group can be misinterpreted because of the potential presence of

transient maternal antibodies.

Cessation of intake into the shelter is critical for effective out-

break management. If temporary cessation of intake is not possible,

then housing newly admitted dogs in a completely segregated area of

the shelter (with infection control practices, including designated

staff and equipment) is required to prevent disease transmission.

Utilization and Interpretation of

Serologic Titers

In human medicine, the efﬁcacy of modern vaccines is established

and monitored primarily on the basis of standardized serology

(“titers”) in conjunction with large-scale clinical trials and usually

substantial centralized disease-reporting processes from vaccinated

populations.

111

A similar approach has been applied to some extent

in livestock medicine. This has been facilitated by large vaccinated

populations and driven by economic imperatives; immunity favor-

ably affects production parameters. Data deriving from such studies

are nearly absent in canine populations.

Studies of experimental infections to determine vaccine efﬁcacy

in dogs generally involve small numbers of animals and may use

challenge organisms and methods that do not reproduce naturally

occurring diseases. In addition, vaccine efﬁcacy and licensing studies

generally use purebred beagles with limited genetic heterogeneity.

There are relatively few studies conducted in household dogs. Under-

standing these limitations, as well as the biological reality that vac-

cines almost never protect 100% of the population 100% of the time,

is essential to convey reasonable expectations of vaccine efﬁcacy to

clients.

“Protective titers” forCDV,CPV,andtoalesserextentCAV-1

have been of most interest to general practitioners. These viruses

often cause lethal infections in naïve dogs and comprise the core

antigens for which there are very effective vaccines. Generally, labo-

ratories determining titers have used VN tests for CDV and HI tests

for CPV.

112–114

Both are bioassays and report results as titers, which

are dilutions of antibody. Both VN and HI tests measure antibodies

to viral surface proteins that directly relate to neutralization of the

virus (VN) or are a surrogate for actual neutralization (HI). In con-

trast, depending on how the test antigen is prepared, ELISA tests can

measure antibody responses that are not involved in protection, such

as responses to internal nuclear proteins. Results are generally

reported as “units,” not titers.

Interpretation of titers can be difﬁcult for several reasons. First,

by their nature, they are subject to intralaboratory and interlabora-

tory variation. This issue was at least implied in seminal stud-

ies.

112,113

Second, there is no readily available documentation of

standardization or comparative results of these or other tests when

performed in different laboratories. This makes it difﬁcult to inter-

pret a titer, especially if it is not very low or very high. Lastly, at best,

the determination of “protective titers” hasbeenbasedonlimited

data. These data were thoroughly reviewed 20 years ago.

112

Nothing

more substantive has become available since then. ELISA-based in-

clinic antibody detection tests have been available for CPV and CDV

for more than 20 years.

115,116

HI and VN tests, respectively, were

used as “gold standards” to determine their sensitivity and speciﬁcity,

as it relates to a “protective titer.”

115–117

Commercial ELISAs have

been applied in shelter populations outside of the laboratory and fur-

ther compared with HI and VN tests.

117,118

Such applications have

provided no further basis for a determination of “protective titers,”

primarily because the titers or amounts of antibody were not corre-

lated with clinical outcomes. Recognizing these limitations, no values

for “protective titers” are indicated in these guidelines, although

some commercial laboratories will provide them.

After the disappearance of maternal antibodies, the presence of

any detectable antibody (a titer) indicates, by deﬁnition, that an

immune response to vaccination or exposure to an antigen involving

at least B and helper (CD41) T cells has occurred.

The presence,

or absence, of antibody is not necessarily indicative of coincident

cell-mediat ed immune responses, or their absence.

Altogether, a

titer, almost regardless of the amount, is not necessarily indicative of

protection or susceptibility. Rather, it is more complicated than

that.

119

Disease in the individual animal results from the interaction

of host, pathogen, and environmental cofactors. It can be misleading

to forecast an outcome on the basis of one cofactor: a titer.

Routine administration of commonly used vaccines has been

associated with uncommon to rare adverse events in dogs.

52,120

Cur-

rently, for the core antigens, most practicing veterinarians have

adopted a 3 yr protocol. Unlike in human medicine, it is based on

very limited population-based data involving disease reportage, and

experimental challenge studies directly comparing the responses in

annually versus triennially (or any other interval) vaccinated dogs

are lacking. Altogether, routine “titer testing” to ascertain the neces-

sity to revaccinate at currently recommended intervals is not usually

advised, except in cases in which dogs have a history of adverse

responses to vaccination, there is a suspicion of vaccine-related auto-

immune disease, or when owners express resistance or hesitancy to

2022 AAHA Canine Vaccination Guidelines

JAAHA.ORG 11

having their dogs vaccinated or boostered—in which case client com-

munication and education may help overcome this hesitancy.

Postvaccination Adverse Events

and Reactions

Undesired or unexpected consequences after vaccination include fail-

ure to provide protection from disease and adverse reactions associ-

ated with vaccine administration. Failure to provide protective

immunity is primarily of concern in very young or very old dogs.

Young dogs most commonly fail to mount a sufﬁcient immune

response following vaccination because of the presence of MDA

from colostrum. Puppies in some breeds, e.g., Doberman pinschers

and rottweilers, have been purported to be immune nonresponders

to a standard initial vaccination series, but deﬁnitive evidence of this

characteristic is lacking.

Questions are sometimes raised about whether multiple vac-

cines, simultaneously administered, diminish or overwhelm the

immune response. Although antibody responses can vary after

administration of different vaccines and antigens, there is no evi-

dence of a lack of protective immunity following concurrent admin-

istration of multiple antigens or vaccines.

Vaccine efﬁcacy in older dogs is typically related to concerns of

immunosenescence, an age-related decline in the function of the

immune system. Although geriatric dogs may have a relative diminu-

tion of naïve T cells to confront new antigens, these patients gener-

ally do not lack memory cells created from previous exposure to

antigens in early or mid-life.

121

Adverse postvaccination reactions may be (1) caused by inap-

propriate administration of a modiﬁed-live product, (2) secondary to

innate immune responses to the vaccine, (3) speciﬁc cell-mediated or

humoral immune responses to vaccine components, or (4) induced

by vaccine antigens that return to virulence (unlikely in appropriately

tested and licensed vaccines).

Localized cell-mediated immune reactions or generalized sys-

temic responses can occur after vaccination. Type I hypersensitivity

reactions have been linked to vaccination, but vaccine associations

with other immune-mediated diseases, e.g., immune-mediated throm-

bocytopenia, immune-mediated hemolytic anemia, and immune-

mediated polyarthritis, are less consistent.

122–126

This may indicate

that factors besides vaccine antigens are respon sib le for immune

disease sequelae following vaccination.

Adverse reactions, as well as desirable immune responses, are

genetically inﬂuenced in some cases. Immunogenetics is a developing

investigative ﬁeld for adverse drug and vaccine reactions in peo-

ple

127,128

but is basically unexplored in veterinary medicine.

Although some breeds have been identiﬁed as at increased risk of

vaccine reactions,

breed (a phenotype) is a crude indicator of

genetics. More likely, genetic predisposition for individuals exists

within some family lines, thus selectively increasing risk overall for

some breeds. Owners should be informed that adverse event risk

occurs at the individual patient level.

129

In genetically predisposed individuals, undesirable immune

responses can be triggered by various vaccine antigens.

123,130

In dogs,

IgE reactivity has been detected against components of cell culture

media used to propagate vaccinal viruses and other pathogens. Mostly,

the offending substances are xenogeneic (to dogs) proteins, such as in

fetal calf serum, e.g., bovine serum albumin, gelatin and casein.

131

other words, the antigens of concern are typically vaccine components

that are not the label (pathogen) antigens. Thus, identiﬁcation and

quantity of these antigens are not part of manufacturer labels.

Although genetic predisposition cannot be altered, adverse

event risk can be diminished by reducing the quantity of vaccine

antigens presented to the patient’s immune system. Because antigens

of concern are not the label antigens, combination vaccines contain-

ing multiple pathogens do not inherently carry more adverse event

risk than single-component vaccines. Because of the way rabies vac-

cine virus is propagated, single-component rabies vaccines may have

more adverse event risk, as they have a more diverse array of pro-

teins than combination vaccines containing other viruses that are

propagated similarly, or other single-component vaccines.

132

Reducing antigenic stimuli can be achieved by reducing the

number of vaccines administered at a single ofﬁce visit. This is a par-

ticularly useful approach in small dogs.

Reducing the administered

volume (“split dosing”) for any vaccine below the manufacturer’s

recommended volume is not advised, because the USDA and manu-

facturer have not approved such reductions. Therefore, this practice

couldinvolvetheassumptionofliability.

Reducing the number of vaccines administered at a single ofﬁce

visit may necessitate additional ofﬁce visits in order to provide neces-

sary vaccine coverage and complete protection. Although compari-

son studies have not been performed, at least 2 wk is recommended

between vaccines to allow the heightened immune response from the

most previous vaccination to subside.

If possible within guidelines and manufacturer recommenda-

tions, administering vaccines nonparenterally, e.g., mucosally or IN,

can also reduce adverse event risk.

A common question is whether at-risk patients should be

pretreated with diphenhydramine before vaccination. If the risk is

hypothetical, i.e., involving an at-risk breed but in cases in which no

previous reactions have occurred, pretreatment as a precaution is

generally not recommended. Although prevaccination administration

of diphenhydramine may prevent type I hypersensitivity reactions,

the lack of any subsequent reaction does not actually prove the pre-

treatment was beneﬁcial or necessary.

12 JAAHA | 58:5 Sep/Oct 2022

If the vaccination risk involves a dog with a history of previous

vaccine reaction, one cannot presume reactions will automatically

recur. Precautions such as limiting the number of vaccines adminis-

tered are prudent, as is prevaccination administration of diphenhy-

dramine. Single anti-inﬂammatory doses of glucocorticoids, if

administered, do not impair humoral responses to vaccination.

133,134

If the vaccination risk involves a patient with an existing immune-

mediated disease, consideration should be given to the stability and

condition of the patient, the need for vaccination, and prudent ways

to minimize adverse event risk.

If vaccines are administered to patients with existing medical

conditions or health concerns, clients should sign an informed con-

sent statement as increased risk of disease may result if the dog’s

immunocompetence is compromised. When a dog experiences a

possible adverse event, the veterinary team should report the speciﬁc

patient and vaccine infor mation to the vaccine manufa cturer

and/or the USDA. (https://www.aphis.usda.gov/aphis/ourfocus/

animalhealth/v eterinary-biologic s/adverse-event -reporting/ct_

vb_adverse_eve nt).

Vaccine Storage and Handling

Vaccines are among some of the most important resources used to

protect animals’ health. However, they are only effective if they are

stored and handled correctly. Improper handling and storage can

decrease the efﬁcacy of the vaccine, leaving the animal vulnerable to

disease.

135

Speciﬁc details about storage and handling protocols can

be found in each manufacturer package insert.

In general, storage and handling require vaccines to be kept in a

temperature-controlled environment from the time they leave the

manufacturer to the time of their administration, a process known as

the vaccine cold chain.

135,136

The vaccine cold chain is a shared

responsibility between the manufacturer, distributor, and veterinary

team. The development of a standard operating procedure to ensure

proper ordering, storage, and administration is essential to the vac-

cine protocol of a veterinary healthcare provider.

Storage and temperature monitoring equipment are critical to

ensure proper vaccine potency. The CDC recommends purpose-built

units (also known as pharmaceutical grade) or stand-alone house-

hold refrigeration units to properly store vaccines.

135,136

Either

purpose-built or stand-alone units can be compact size or larger. A

high-quality thermometer should be kept in the center of the refrig-

erator. Temperatures should be monitored and recorded per the vet-

erinary team’s standard operating manual.

Refrigerated vaccines should be stored at temperatures between



Cand8



C(36



Fand46



F).

135,136

The thermostat should be set at

midrange to achieve a temperature of 5



C(40



F), which will

decrease the likelihood of temperature ﬂuctuations.

135,136

Vaccines

should be organized and placed centrally in the refrigeration unit to

promote proper airﬂow, typically 2–3 inches from the walls and

doors.

135,136

Removedeli,fruit,andvegetabledrawers,astheseareas

have unstable temperatures and are unsuitable for storage. Vaccines

should be kept in their original packaging with lids closed until ready

to open.

135,136

The refrigerated vaccine storage unit should be desig-

nated for only vaccines.

Single-dose vaccines (both freeze-dried and liquid forms)

should not be removed from the refrigerator until the time of admin-

istration.

135,136

A new, sterile syringe and needle should always be

used for proper vaccine administration. A delay in vaccine reconsti-

tution and administration could decrease the efﬁcacy of the vaccine

owing to the fragility of the vaccine and temperature ﬂuctua-

tions.

135,136

Multidose vaccines typically have preservatives to allow

prolonged storage once the seal has been opened.

135,136

See the vac-

cine package insert for manufacturer recommendations and direc-

tions for proper storage and handling.

Interpreting Vaccine Labels

Labels for veterinary vaccines have recently undergone considerable

changes to bring greater clarity to the user. Historically, veterinary

vaccines were assigned a tier system based on the effectiveness of the

protection of the vaccine.

137

The tier system was initially not well

understood and led to confusion among veterinary practitioners. As

a result, the USDA implemented a new rule that requires vaccine

labels to contain a simple claim and provide the public the opportu-

nity to view the relevant safety and efﬁcacy studies online.

137,138

The

new label system states: “This product has been shown to be effective

for the vaccination of healthy (name of species, weeks of age or older

against name of disease).

137

Veterinarians are encouraged to review

individual manufacturer efﬁcacy and safety data online at the

Licensed Biological Product Information website: https://www.aphis.

usda.gov/aph is/our focus/an imalhe alth/ve terinar y-biolo gics/C T_

Vb_licensed_products.

Vaccine Licensure

In the United States, veterinary biologics include vaccines, bacterins,

antisera, diagnostic test kits, and other products of biological origin

acting through immunologic mechanisms to prevent disease.

139

The

USDA, under the authority of the Virus-Serum-Toxin Act, governs

and mandates the licensure of biologics.

139

The USDA prohibits the

preparation or sale of veterinary biologics that are ineffective,

contaminated, dangerous, or harmful.

140

The mandate of the Virus-

Serum-Toxin Act is interpreted with the understanding that veterinary

biologics should be safe, pure, potent, and efﬁcacious.

140

Regulatory over-

sight through the USDA Animal and Plant Health Inspection Service

is described in 9 CFR 101-124. In the United States, manufacturers

2022 AAHA Canine Vaccination Guidelines

JAAHA.ORG 13

are inspected before the issue of their ﬁrst license for a product and

then periodically inspected afterward. Not only are the physical

plants inspected, but starting materials (seed virus, bacteria, and cell

lines) are also tested for purity and identiﬁcation.

137

Once a license

has been granted, no substantial changes in the manufacturing pro-

cess are allowed to ensure a consistent product.

137

Vaccines are granted different licenses through different catego-

ries.

137

Fully licensed products meet the requirements that establish the

purity, safety, potency, and efﬁcacy of the product. Conditional licenses

are issued in order to meet an emergency condition, limited market,

local situation, or other special circumstance under expedited proce-

dures that ensure purity, safety, and a reasonable expectation of efﬁ-

cacy. Imported products can be permitt ed for distrib ution and sale and

must meet the same standards as fully licensed products. This scenario

is typically associated with factors such as a lack of USDA-licensed

products and a viable threat of emerging infectious animal disease.

137

The licensure standards for veterinary vaccines in Canada are

similar to those required in the United States for fully licensed prod-

ucts. Regulated products include vaccines, immunoglobulin prod-

ucts, and diagnostic kits that are used for the prevention, treatment,

or diagnosis of diseases in animals, including domestic livestock,

poultry, pets, wildlife, and ﬁsh. To meet the requirements for licen-

sure, veterinary biologics must be shown to be pure, potent, safe, and

effective when used in the target species according to the manufac-

turer’s label recommendations. Product labeling must be compliant

with Canadian requirements, including the use of metric units and

complete information available in both English and French. The

CFIA, under the legislative authority of the Health of Animals Act

and Regulations, is responsible for regulating veterinary biologics in

Canada.

141

Responsibilities of the CFIA in licensing vaccines include

veriﬁcation of products (master seeds), licensing of the manufactur-

ing facilities, and issuance of import and/or export permits.

141

addition, the licensing submission must also contain supporting data

demonstrating that the product can be manufactured and used with-

out adversely affecting animal health, human health, food safety, or

the environment.

141

Client Education and Training the

Healthcare Team

Creating a well-deﬁned vaccination protocol with consistent messag-

ing serves as a framework for the veterinary team to reference during

patient visits. This reinforces the importance of vaccines for the vet-

erinary team and ensures that a consistent message is communicated

between the healthcare team and clients. A protocol also helps the

healthcare team follow a consistent vaccination schedule, especially

when starting an initial series of vaccines, while concurrently consid-

ering the lifestyle, geographical location, and risk factors for each

individual pet. At a minimum, a vaccination schedule should consist

of the following information:

 Anatomical location of vaccine administration

 Route of administration

 Age requirements and/or restrictions

 Frequency of administration

A vaccination protocol should be created with the patient’s

needs and lifestyle in mind, with buy-in from the client through edu-

cation explaining the importance of vaccines.

The Need for Consistency

Creating consistency across the healthcare team builds a strong prac-

tice culture, decreases confusion about recommendations, assists with

training team members, and increases compliance. This better enables

all team members to educate clients about vaccination schedules,

disease prevention, and what to expect following vaccination. Client

education materials can support practices by educating clients about

vaccinations, vaccine reactions, and disease processes.

Wellness plans prove to be advantageous by creating consis-

tency within a practice and providing a standard for quality pet care.

Wellness plans often include the recommended vaccinations for pets

and help the healthcare team deliver a clear message when it comes

to the health of the dog. They can also reduce redundancy in deliver-

ing key points about certain vaccines, vaccination protocols, and the

importance of vaccination.

Developing Client Education Materials

Client education continues even after a dog presents to a practice for

vaccination. Developing client education materials and creating a

practice library can provide a ready resource to clients about why,

what, and when vaccines should be given to their pet. The more cli-

ents understand the reasons for vaccination, the more likely they will

see the importance of adhering to an individualized vaccination

schedule for their dog. Each practice should consider creating a

source (online or physical copies) of educational material for clients,

discharge instructions for practice teams, and short blurbs of 1–2

sentences about each vaccine and the disease(s) it prevents. More

comprehensive educational material can be stored in a repository

and used as requested or needed.

Determining the Best Communication

Approach

In order to determine how to best communicate with clients, it is

important to assess client communication preferences. A survey or

questionnaire can be used to ask clients about their preferred contact

methods or whether they would like to receive speciﬁc additional

14 JAAHA | 58:5 Sep/Oct 2022

material. Client preferences can then be noted in the patient’shistory.

This allows information to be relayed in a way the client understands.

With electronic medical record systems now in veterinary practices,

documenting and ﬁnding client information has simpliﬁed. Some

electronic medical record systems can even connect with mobile appli-

cations where clients and hospital teams can communicate.

Summary

Regular vaccination of canine patients is a central component of pre-

ventive healthcare, as well as an opportunity for the practice to engage

with clients to discuss the importance of disease prevention. These

vaccination guidelines provide a current and comprehensive resource

for making informed decisions when designing vaccination protocols

for dogs. Vaccination best practices are based on individualized needs

determined by the patient’s history and risk of disease exposure.

Whereas core vaccines are recommended for every dog regardless of

lifestyle, noncore vaccine recommendations are determined by assess-

ing the likelihood of a dog’s exposure to a given infectious disease.

Licensed canine vaccines have a high degree of safety and efﬁcacy,

and in most cases, the beneﬁts of vaccination far outweigh the risks.

Dogs presented at, residing in, or originating from animal shelters are

in a high-risk setting for infectious disease exposure and outbreaks,

and shelter-speciﬁc vaccination protocols seek to mitigate that risk.

It is important that the entire healthcare team be well versed on

the practice’s vaccination philosophy and protocols. The practice team

is then prepared to deliver a consistent and uniﬁed message to clients

on the importance and role of vaccination in patients’ healthcare

plans. Improper vaccine storage and handling and failure to adhere to

label recommendations are the principal reasons for the occasional

incidence of vaccination failure. Periodic staff training can minimize

these procedural shortfalls and help ensure that vaccination is a reli-

able and useful tool for delivering optimum pet healthcare.

The authors gratefully acknowledge the contribution of Mark

Dana of Kanara Consulting Group, LLC, in the preparation of

the manuscript.

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