Vaccination is widely employed to protect dogs against infectious diseases. As might be anticipated, some of these diseases are more important than others. This has led to the designations “core” and “noncore” to denote those vaccines that are essential and those that are less important. Core vaccines are those that all dogs, regardless of circumstances or location, should receive. They protect the animals from severe, life-threatening disease. The three core vaccines for dogs in North America are those against canine distemper virus (CDV), canine adenovirus 2 (CAV-2), and canine parvovirus type 2 (CPV-2). Additional vaccines may also be considered to be essential by the attending veterinarian based on their professional judgment. One obvious such example is rabies vaccine, especially in countries where rabies is endemic. Rabies vaccination is also legally required in many jurisdictions and is mandatory for international travel. Noncore vaccines are those whose use is also based upon careful risk assessment by a veterinarian in consultation with the dog owner. These risks will vary with the type of vaccine used, geographic location, local environment, degree of exposure to other dogs, and the dog’s lifestyle (Box 13.1). One unique feature of dogs is their extreme size variation. This presents problems regarding vaccine safety and efficacy. It has been conventional procedure to administer an identical dose of vaccine to all dogs irrespective of their size. Although it has long been thought that the canine immune system was somewhat indifferent to antigen dose, this is not the case. Postvaccinal antibody titers vary inversely according to a dog’s body weight. For example, antibodies against CPV-2, CDV, and CAV-2 have been measured in adult dogs over a large size range, 12 months after receiving a conventional vaccine. All the dogs developed a protective level of antibodies. CPV-2 antibody titers were significantly higher in very small dogs (<5 kg) than in medium sized dogs (10–20 kg) or in large dogs (>20 kg). CDV antibody titers were significantly higher in the very light, light, and medium groups, than in the heavy group. Interestingly there were no significant differences between the size groups with respect to CAV-2 antibody titers. In another study investigating rabies vaccine failures, the proportion of dogs failing to make sufficient antibodies—their median antibody titers—decreased whereas the vaccine failure rate increased with increased dog sizes. There is also a difference in the frequency of adverse reactions to vaccination in dogs depending upon their size (Fig. 10.1). Small dogs suffer more adverse events than large dogs. Other issues associated with dogs are the major differences in vaccine responses associated with different breeds. These breed differences, resulting largely from a loss of genetic variability, are reflected in differences in their responses to vaccines and also differences in their susceptibility to vaccine-induced adverse events. Bordetella bronchiseptica is a gram-negative bacterium, one of the complex mixture of agents that are associated with canine respiratory disease. Its importance was recognized in 1910 when it was wrongly believed to be the cause of canine distemper (Chapter 1). B. bronchiseptica is a primary pathogen because it can impair ciliary function and thus predispose to secondary opportunistic infections. It can also be a secondary invader following infection with other respiratory pathogens. Bordetella infection is associated with mild to moderate tracheobronchitis resulting in coughing, retching, sneezing, and nasal discharge. Monovalent and combined vaccines are available for administration parenterally or intranasally. Most of these are combined vaccines that contain multiple antigens against diverse respiratory pathogens. A nonadjuvanted acellular B. bronchiseptica vaccine containing selected bacterial antigens may be administered by the subcutaneous route. Several different modified live intranasal B. bronchiseptica vaccines are also available as well as single component oral vaccines. The oral vaccines may be administered into the buccal pouch as early as 7-8 weeks of age. Onset of immunity develops by 48 hours following oral and intranasal vaccination and the duration of immunity is 12 to 14 months so annual revaccination is recommended. These vaccines may be administered in combination with canine parainfluenza and CAV-2 vaccines. Intranasal or oral vaccines must never be delivered by parenteral injection since these live vaccines retain some virulence and may therefore cause severe adverse reactions and possibly death. Leptospira are aerobic gram-negative spirochetes. The taxonomy of Leptospires is complex and confusing. Three species are common animal pathogens, Leptospira interrogans, Leptospira borgpetersenii, and Leptospira kirchneri. These are each divided into multiple serogroups and serovars (Table 13.1). More than 250 serovars of Leptospira have been identified and immunity is highly serovar specific. Before the introduction of vaccination, the important serovars were considered to be canicola and icterhaemorrhagiae. Following the widespread use of vaccines against these two, the prevalence of serovars has changed. In North America, the important serovars are now considered to be Pomona, Autumnalis, Bratislava, and Grippotyphosa, whereas in Europe the important serovars are Bratislava, Grippotyphosa, and Sejroe. TABLE 13.1 ■ Note that certain serovars such as Hardjo are found in more than one species. Antileptospiral immunity is primarily antibody-mediated and is directed against the bacterial lipopolysaccharide (LPS). (Experimentally, polyclonal and monoclonal antibodies against this LPS can transfer immunity to susceptible animals.) However, it also appears that cell-mediated responses are required to protect against some serovars such as Hardjo in cattle. Whole, inactivated Leptospira bacterins have been used for many years but are associated with adverse reactions, in addition to serovar-specific immunity. In the United States, dogs receive bacterins containing four serovars: Canicola, Icterhaemorrhagiae, Pomona, and Grippotyphosa. There is limited cross protection between these serovars. Some may protect against clinical disease and reduce but not prevent renal colonization and shedding. Antibodies last for about 1 year (at least 15 months in the case of Grippotyphosa). In other countries these bacterins may contain up to 8 different serovars. (Box 13.2). Borrelia burgdorferi is the cause of Lyme disease predominantly spread by the deer tick, Ixodes scapularis. Four different vaccines are available in North America. All induce antibodies to OspA, the antigenic outer membrane lipoprotein of the spirochete. OspA is expressed by the organisms within the tick mid-gut but is downregulated within the vertebrate host. When blood is ingested by a feeding tick, the antibodies to OspA attack the spirochetes and thus halt transmission. AntiOspA antibody titers are however not boosted by natural exposure and wane in vaccinates allowing host infection. Recently vaccines containing OspC have also been investigated. OspC is the dominant surface antigen expressed within the vertebrate host. AntiOspC antibodies and T cells induced by these vaccines may therefore eliminate organisms within the host. Available vaccines include a killed whole cell bacterin (OspA), a bacterin containing OspA and OspC, a recombinant OspA vaccine and a chimeric recombinant containing OspA plus OspC. All are administered subcutaneously. The reported efficacies of these vaccines are highly variable ranging from 50% to 100%. Vaccination of infected dogs is of no benefit so puppies should be tested to ensure that they are not infected before vaccination. Vaccination is also advisable if a dog travels from a nonendemic area to an endemic one. Vaccination must be part of a comprehensive program to reduce disease risks including adequate tick control, preferably with products that prevent tick attachment or kill ticks during early feeding. As with other species, dogs may suffer from chronic infectious respiratory disease caused by diverse pathogens. An initial viral infection may cause tissue damage and immunosuppression leading to secondary bacterial invasion. The primary viral pathogens include canine parainfluenza, adenovirus 2, or distemper. Other viruses that may play a role include reoviruses, respiratory coronavirus, herpesvirus, influenza virus, pneumovirus, and adenovirus 1. Bordetella bronchiseptica may act as a primary or secondary pathogen. Other potential bacterial pathogens include Mycoplasmas, Streptococcus equi subspecies zooepidemicus, and Chlamydophila psittaci. Vaccines are not available against every one of these agents and the viral components are discussed in the viral section later. Many of the available vaccines are designed to be administered intranasally. It should be pointed out that there are major differences in the nature of the immune response triggered by intranasal and injected vaccines. Thus intranasal administration with a modified live vaccine will trigger local innate responses in addition to a local immunoglobulin A (IgA) response. Parenteral immunization with an acellular vaccine will trigger a systemic immunoglobulin G (IgG) response. Both of these are protective responses. In theory, the best result may be obtained by administering the injected vaccine first and boost with the intranasal product (or vice versa). This prime boost technique has worked very well in humans vaccinated against polio. However, there is as yet, no data to support this method in dogs. Canine distemper caused by canine morbillivirus infection remains one of the most significant and lethal viral diseases of dogs. It affects the gastrointestinal and respiratory tract in addition to the nervous system. There are currently 50 licensed distemper vaccines available in the United States; however, only one of these is directed against canine distemper virus alone. Distemper vaccine is usually combined with those against canine adenovirus 2, canine parvovirus, and canine parainfluenza. These combinations may also contain coronavirus, leptospirosis, and Borrelia vaccines. Three different types of vaccine are available to prevent canine distemper. Inactivated CDV vaccines generally give inferior protection and are best used in susceptible wildlife species. Modified live virus vaccines contain attenuated virus strains such as the Snyder Hill and Rockborn strains attenuated by prolonged canine cell culture, or the egg adapted Onderstepoort strain, now adapted to tissue culture. Antigenic differences between these strains are not significant and all are protective when used appropriately. Note that the modified live virus (MLV) distemper vaccines, although safe in domestic dogs, can cause disease in related wildlife such as gray foxes and the black-footed ferret. Indeed, the black-footed ferret, a highly endangered species was nearly wiped out as a result of the inappropriate use of MLV distemper vaccines (Chapter 20). A canarypox vectored recombinant vaccine is available in some countries. The genes encoding two immunogenic CDV antigens, the hemagglutinin (HA) and fusion proteins have been inserted into an ALVAC canarypox vector (Chapter 5). This vaccine is able to overcome some maternal immunity and appears to immunize puppies about four weeks earlier than conventional MLV vaccines. The vectored vaccine has the additional advantage that it is unable to cause postvaccinal distemper encephalitis. The recombinant and MLV vaccines perform similarly with respect to onset and duration of immunity. Measuring serum antibodies provides a reasonable assessment of protective immunity. Duration of immunity after vaccination is at least five years. Measles and canine distemper viruses are very closely related morbilliviruses; their fusion proteins are almost identical. As a result, an attenuated measles vaccine has been used for many years to provide early protection of puppies against distemper. The differences between the HA antigens of these viruses are such that maternal antibodies against distemper virus cannot completely neutralize the measles vaccine. As a result, measles vaccine may be administered somewhat earlier than distemper vaccine to effectively immunize puppies. It is given intramuscularly between 6 and 12 weeks of age. (Use the dog vaccine, not the human one. There is not enough antigen in the human one.) It is vitally important, however, that puppies also be vaccinated using a distemper vaccine at the appropriate time. Heterotypic immunity should not be relied on after 16 weeks of age. CAV-2 is a respiratory pathogen transmitted by the oronasal route. The virus damages bronchial epithelial cells resulting in fever, cough, nasal discharge, and pharyngitis. Inactivated CAV vaccines are usually administered in combination with CDV and CPV. The preferred vaccines against canine adenoviruses are modified live products. These MLV also provide immunity against infectious canine hepatitis caused by CAV-1 and against tracheobronchitis caused by CAV-2. Immunity develops about five days postvaccination with the MLV. However, CAV-2 infection or vaccination will not induce the hypersensitivity reaction known as blue-eye caused by CAV-1 (Fig. 10.5). Both injectable and intranasal forms of CAV-MLV vaccines are available. Because CAV-2 is a contributor to the canine respiratory disease complex, it is commonly used in combination with other respiratory pathogen vaccines such as those against Bordetella bronchiseptica and canine parainfluenza virus. The duration of immunity after vaccination is at least nine years. The presence of serum antibodies indicates protection, making serology a useful guide to revaccination. CPV is one of the major causes of canine acute gastroenteritis. Young puppies two to six months of age are most susceptible, but cases are increasingly recognized in adult dogs. Clinical signs include anorexia, depression, vomiting, and diarrhea that is often hemorrhagic. The original canine parvovirus (CPV-2) first appeared in the 1970s and was likely a host variant of feline panleukopenia or a related virus. Since then new circulating variants have appeared. For example, CPV-2a and -2b appeared in the 1980s and CPV-2c in 1996. All these variants are antigenically related so that currently available MLV-CPV vaccines are believed to protect against the variants circulating in North America. The inactivated vaccines are not as effective and are relatively slow to induce protective immunity when compared with the MLV vaccines. As a result, they are not recommended for routine use except possibly in situations such as in an immunosuppressed dog where the use of a live vaccine may be hazardous. In the absence of maternal antibodies, MLV parvovirus vaccines may be protective within three days. This is probably because of early interferon production rather than antibodies (Fig. 4.1). These MLV vaccines can replicate in the dog intestine and thus are intermittently shed in the feces of vaccinated dogs. This shedding occurs irrespective of the presence of antibodies. MLV-CPV vaccines should not be used in wildlife as they may be insufficiently attenuated. Inactivated vaccines are safer in other species. Duration of immunity is thought to be life-long, especially following the use of MLV vaccines. The use of rabies vaccines in the United States is regulated by individual states or other jurisdictions. As a result, requirements may be conflicting and inconsistent. In most, but not all states, vaccination is mandatory. It is essential that practicing veterinarians are fully aware of the appropriate legislation and regulations that govern rabies vaccination. Although modified live vaccines have been proven safe in dogs, the World Health Organization stopped recommending these vaccines in 2004. As described elsewhere (Chapter 10), self-inoculation incidents result in an unacceptable risk to humans. No modified live rabies vaccines are currently marketed in the United States. Inactivated rabies vaccines are commonly used in mass vaccination programs where maintaining the cold chain is less critical and safety is not an issue. These viruses are generally grown to high titer in tissue culture and then inactivated with beta-propiolactone, acetylethylamine, or binary ethyleneimine (Fig. 3.2). Once inactivated, adjuvants such as aluminum hydroxide, aluminum phosphate, or saponin are added. Vectored recombinant rabies vaccines express the highly immunogenic rabies glycoprotein G gene. Vectors used include vaccinia, canarypox, and adenoviruses. The vaccinia and adenovirus vectored vaccines may be used in North America and Europe for wildlife vaccination. It is interesting to note that injectable rabies vaccines may be of little use in less developed countries where most cases of canine-induced rabies occur. In these countries there are large numbers of stray dogs and it is not possible to catch and vaccinate them all. In such cases, encouraging results have been obtained by distributing oral recombinant vaccines similar to those used in wildlife (Chapter 20). Blister packs containing the vaccines may simply be offered to these dogs by hand, enclosed in chicken heads, meatballs or a short segment of boiled beef or pig intestine. The vaccinator can also note that the dog has punctured the vaccine blister and recover used packs. This technique is a viable strategy to supplement parenteral vaccination in otherwise unreachable dog populations. In many jurisdictions it is a requirement that domestic dogs, cats, and ferrets are to be vaccinated. In general, they are not considered to be vaccinated until 28 days after the initial vaccine dose. The interval between doses is determined by the manufacturer and indicated on the product label, but legally they are considered unvaccinated one day after the vaccine’s official duration of immunity (one year or three years). In most (but not all) states, only a licensed veterinarian is authorized to administer rabies vaccine. The definition of exposure to rabies also varies between states. This is determined by the state Department of Health, not by the veterinarian. Most properly vaccinated dogs are immune to rabies. Should such a dog be bitten by a rabid animal, they should be quarantined for 45 days. Unvaccinated animals should be quarantined for four months. They should be vaccinated within 96 hours of exposure on entry into quarantine. If multiple doses of vaccines are administered to small-breed dogs (<10 kg), this may increase the risk of adverse reactions. Given the importance of the size of the dog, it has been suggested that veterinarians consider delaying administration of noncore vaccines to small dogs until two to four weeks after completion of the core vaccination process. There is currently no data available to support the practice of reducing vaccine dose or frequency of administration in small dogs. Dose reduction increases the chances that the dog will receive an insufficient dose to confer protective immunity. Likewise, there is no data to suggest that dose reduction will reduce the incidence of adverse events. After all, if the animal is already allergic to a vaccine component, even a reduced dose may trigger a reaction. Note that vaccination of dogs against rabies has saved millions of humans from a horrible death. This is yet another triumph for the science of immunology. Canine parainfluenza (CPiV) is a Rubulavirus in the family Paramyxoviridae. It is one of the main contributors to “kennel cough.” The virus causes transient mild respiratory disease and damages local defense mechanisms in the respiratory tract by destroying ciliated epithelium. As a result, secondary opportunistic infections by viruses and bacteria are common. It is usually a component of combination vaccines. The duration of immunity to this virus is unclear and it may be less than three years. Canine influenza was first described in 2004 when it appears to have been transmitted from horses to racing greyhounds. The original outbreak began as a severe hemorrhagic pneumonia with high mortality. Viral virulence has declined since then and the canine disease is now primarily a tracheobronchitis. An inactivated canine influenza vaccine (H3N8) may be given subcutaneously. Immunity develops approximately seven days after the second dose although vaccinated dogs may still develop mild clinical signs. This is a noncore vaccine because this strain of influenza is largely restricted to North America. An inactivated influenza vaccine against a second influenza strain (H3N2) is also available as is a bivalent vaccine directed against both strains. This strain of influenza is also currently geographically restricted to North America. H3N2 is shed in much greater amounts than H3N8, making it that much more contagious. Ideally dogs should receive vaccines against both strains if the veterinarian perceives them to be at risk. Influenza viruses continue to evolve rapidly. The highly pathogenic strain of influenza, H5N1, was transmitted to dogs in Central Asia after they had been exposed to infected duck carcasses. It is essential that veterinarians be aware of the inevitability of the emergence of new strains of influenza virus capable of infecting both companion animals and their owners. Most of the vaccines used in dogs contain combinations of antigens. These are generally administered as subcutaneous modified live or recombinant canine distemper vaccine (D) plus adenovirus 2 (A), parvovirus (P), and parainfluenza (P) vaccines (DAPP). Other vaccine combinations may include leptospira. There are two groups of canine coronaviruses. Group 1 causes enteric disease. Group 2 causes a mild self-limiting respiratory disease. Although both inactivated and modified live vaccines against the group 1 virus are available, their use is not usually recommended because this virus usually only causes a mild, self-limiting or inapparent gastroenteritis with anorexia, fever, and diarrhea. It usually affects puppies younger than six weeks old and lasts for a few days. The vaccine appears to protect dogs from disease but not from infection. Canid herpesvirus 1 may produce mild upper respiratory disease and inapparent infections in adult dogs. However, it causes fatal infections in newborn puppies. This susceptibility is highly age related and puppies over two weeks of age rapidly develop resistance. The clinical disease is nonspecific. Puppies vomit, show rapid shallow breathing, and die within two days. The virus may also cause abortion, stillbirth, and infertility. Although a vaccine is not available in North America, an adjuvanted subunit vaccine is marketed in Europe (Eurican Herpes 205, Boehringer Ingelheim). It consists of purified glycoprotein subunits (especially gB glycoprotein) of the F205 strain with an oil adjuvant. It is administered subcutaneously when the female is in heat or 7 to 10 days after mating. A second dose is given one to two weeks before whelping. Revaccination during each subsequent pregnancy is recommended. As with other such vaccines its effectiveness depends upon the puppies ingesting adequate colostral antibodies. A toxoid directed against the Western Rattlesnake (Crotalus atrox) venom is available. It is administered to dogs that may be exposed to Western Diamondback Rattlesnakes. There is limited cross protection against other rattlesnake species. Two subcutaneous doses are given after four months of age, and annually thereafter. Although this vaccine may mitigate the severity of the venom, snake-bitten dogs must still receive immediate veterinary attention. Current high-quality core vaccines induce high levels of antibodies in dogs. As a result, canine colostrum also contains high antibody titers. These maternal antibodies are highly effective in blocking antibody responses in young puppies (Fig. 13.1). As a result, maternal antibodies persist longer and many puppies cannot be primed, even by 12 weeks of age. Most puppies that have suckled successfully and received sufficient colostrum will be protected up to approximately 8 to 14 weeks of age. However, not all mothers are immune and not all puppies receive sufficient colostrum. As a result, at least three doses of the core vaccines must be administered every 3 to 4 weeks beginning between 6 and 8 weeks of age with the final dose administered on or after 16 weeks of age to ensure that a susceptibility gap does not develop between the loss of maternal immunity and vaccination. An optional fourth dose may be administered at 18 to 20 weeks of age. This is recommended if confirmed distemper or parvovirus infections have occurred in young dogs that had received the initial three-dose series.
Canine vaccines
Species considerations
Antibacterial vaccines
Bordetella bronchiseptica
Leptospirosis
Species
Serogroup
Serovar
L. interrogans
Icterohemorrhagiae
Icterohemorrhagiae
Copenhageni
Grippotyphosa
Grippotyphosa
Canicola
Canicola
Australis
Australis
Bratislava
Pomona
Pomona
Kennewicki
Sejroe
Sejroe
Hardjo
Leptospira borgpeterseni
Sejroe
Hardjo
Hardjo-bovis
Australis
Australis
Leptospira kirschneri
Icterohemorrhagiae
Icterhemorrhagiae
Grippotyphosa
Grippotyphosa
Canicola
Canicola
Australis
Australis
Borrelia burgdorferi
Canine respiratory disease complex
Antiviral vaccines
Canine distemper
Heterotypic immunization
Canine adenovirus 2
Canine parvovirus
Rabies
Canine parainfluenza
Canine influenza
Combination vaccines
Other noncore vaccines
Canine coronaviruses
Canine herpesvirus
Crotalid vaccine
Vaccination and maternal antibodies
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Canine vaccines
A Simple Classification of the Most Common Leptospires Discussed in the Text
