key: cord-0008975-qigdebgv authors: Greene, Craig E.; Schultz, Ronald D.; Ford, Richard B. title: Canine Vaccination date: 2015-01-13 journal: Vet Clin North Am Small Anim Pract DOI: 10.1016/s0195-5616(01)50603-8 sha: 04c4637d0e027cb98f7e51e7cd1ccbc0772c15f1 doc_id: 8975 cord_uid: qigdebgv New technologies for vaccine development and infectious disease diagnosis are likely to be introduced in the near future. With this new technology comes the opportunity to vaccinate companion animals against even more infectious agents than is currently practiced in the United States. As we look forward, it becomes particularly important to review current vaccination standards applied to dogs with respect to current knowledge of duration of immunity, awareness of incidence, and likelihood of injurious or even fatal adverse events associated with vaccination, and individual risk factors that dictate which vaccines are most appropriate at which stage of life. GREENE et al sion of the facts that have compelled so many authors to challenge existing vaccination practices. This article is not intended to establish new vaccination standards for dogs, nor should it be used as a template for a national canine vaccination protocol. Nevertheless, change is in the wind, and revised recommendations for canine vaccination can be anticipated. The material presented in this article serves as a guide for clinicians willing to consider proposed canine vaccination recommendations as they apply to individual patients. Table 1 represents a summary of the information presented in this article. Is it really necessary to revise vaccination recommendations for dogs? Many would challenge that premise. After all, vaccination practice over the last 20 years has, in fact, worked well; canine distemper, canine parvovirus, and canine rabies are virtually nonexistent among vaccinates. Yet, despite the obvious successes attributable to companion animal vaccination, veterinarians must be willing to at least review, if not revise, vaccination practice standards as new vaccines are introduced and new vaccine technologies are developed. The objective, quite simply, is to administer the most appropriate vaccine(s) at the most appropriate stage of life and to do so with the best product(s) available. What should not occur is complacency and regimentation with respect to selection and administration of vaccines. Yet, that does happen. The demand among veterinarians that vaccines be simple to administer and timesaving has led to the long-term and widespread use of polyvalent vaccines. Twenty-five years ago, the most commonly used polyvalent products contained three vaccines (distemper-hepatitis-leptospirosis). Today, products containing eight or more vaccines per dose are routinely administered to dogs. Furthermore, polyvalent vaccines are routinely administered annually with seemingly little regard for the actual risk of infection. This is a disturbing trend. Annual administration of polyvalent vaccine implies that each vaccine antigen, whether of bacterial or viral origin, in each polyvalent product induces the same degree of immunity for the same duration in every patient. Immunologically, this is irrational. Depending on the vaccine and based on the results of controlled challenge studies, dogs derive protective immunity that persists for as little as a few months to as long as 7 or more years. 2 , 4,7,14,18,20,25,29,30 Convenience rather than science seems to be the driving force behind conventional recommendations listed on vaccine "labels" (product inserts). Even the 1995 ruling by US Department of Agriculture that manufacturers of new veterinary biologic agents must document the duration of immunity listed on the label (this ruling does not apply Not recommended: Infectious canine hepatitis is uncommon in the United States. Considering the low (to absent) prevalence, the risk of "hepatitis blue-eye" reactions and the fact that CAV-2 cross-protects against CAV-l, use of vaccines containing this antigen is not recommended for use in routine vaccination protocols. Recommended: Demonstrated cross-protection against canine hepatitis (CAV-l) and CAV-2, one of the agents known to be associated with infectious tracheobronchitis. Usually combined with CDV and crv vaccine. Currently, this product is not available as a monovalent vaccine. Adult dogs challenged 7 years after CAV-2 MLV vaccination were found to be protected against the more virulent CAV-l. Optional: Lyme disease has limited regional prevalence. Recommendation for use is limited to dogs with a known high risk of exposure. Optional: Lyme disease has limited regional prevalence. Recommendation for use is strictly limited to dogs with a known high risk of exposure. Most authors recommend the recombinant Lyme vaccine over the killed bacterin for reasons of safety (fewer adverse reactions). Required: MLV vaccines are not available; state and local statutes govern the frequency of administration for products labeled as "I-year rabies." The rabies (I-year) vaccine is generally administered as an initial dose followed 1 year later by administration of the rabies (3-year) vaccine; state and local statutes may dictate otherwise. Required: State and local statutes govern the frequency of administration for products labeled as rabies (3-year); these statutes vary throughout the United States. The rabies (I-year) vaccine is generally administered as an initial dose followed 1 year later by administration of the rabies (3-year) vaccine; state and local statutes may dictate otherwise. to vaccines licensed before 1995) is not likely to change "annual booster" recommendations stipulated by manufacturers. It is important to understand that manufacturers are not mandated to establish the full duration of immunity but only to document what they claim. Studies to establish the maximum duration of immunity that would meet USDA guidelines are not economically feasible. The recommendation that virtually all canine vaccines be administered annually to adult dogs has been embraced by the veterinary profession for many years. Interestingly, however, for most vaccines administered to dogs today, there are no scientific studies at all establishing a 12-month duration of immunity. Vaccine efficacy studies for most vaccines in use today challenged vaccinates just 3 to 4 weeks after the last inoculation. The paradigm that adult dogs and cats require annual boosters for all the commonly administered vaccines is being challenged. We simply cannot continue to arbitrarily administer vaccines without regard for the number and type of vaccine antigens in the product and without realistic consideration of the risk of infection facing the individual animal.l2, 15, 16, 22, 24 Modified live virus (MLV) vaccines have been most effective in protecting dogs against canine distemper. Inactivated whole viral vaccines are not effective; however, a vectored recombinant vaccine is currently available. In puppies, distemper vaccination is performed at 3-to 4-week intervals, with the earliest inoculation being given when the puppy is 6 to 8 weeks of age. Most distemper vaccines used in North America today overcome maternal immunity by the time puppies are 12 weeks of age. Vaccination in puppies is usually continued until they reach 16 weeks of age. Dogs older than 12 weeks of age at the time they are presented for initial vaccination should receive at least two canine distemper virus (CDV) inoculations 2 to 3 weeks apart. The minimum duration of immunity, as determined by challenge, to attenuated (MLV) CDV is at least 7 years for vaccines using the Rockport strain of CDV, although that for vaccines using the Onderstepoort strain is at least 5 years. 2 ,29 The recombinant CDV vaccine is a canary pox-vectored vaccine that expresses distemper fusion and hemagglutinin glycoproteins. 23 Dogs receiving this vaccine must receive at least two doses initially. The reported duration of immunity is at least 12 months. Annual booster vaccination is recommended when using this product. A combined distemper-measles vaccine is still available. At a stage of life when administration of MLV CDV vaccine is expected to fail, measles vaccine is capable of causing a heterotypic immune response in the presence of high concentrations of maternally derived distemper antibody. Some veterinarians still recommend administration of a COVmeasles virus vaccine to puppies between 6 and 9 weeks of age. This product should not be used in female puppies over 12 weeks of age, because maternal antibodies to COV and measles may develop. These antibodies would be transferred to subsequent offspring at a level that could interfere with both measles and COV vaccination in the puppies. Therefore, antibodies would interfere with the protective effects of the MV-COV vaccination and the heterotypic MV would not provide early protection from COV Administration of a combined MLV COY-measles virus vaccine should be limited to those puppies in which the nursing status is unknown or that are likely to face COV exposure as puppies. Measles vaccine is not indicated in dogs over 16 weeks of age. Vaccination for canine adenovirus infection, the cause of infectious canine hepatitis (ICH), is usually done in combination with that for distemper and other diseases beginning when puppies are 6 to 8 weeks of age. Attenuated (MLV) adenovirus vaccines are generally used in the United States because of their ability to produce a superior immune response, but inactivated products are still available in the U.S. and marketed in many countries. Vaccination for ICH reduced the prevalence of a disease that was once widespread. Outbreaks or isolated cases still occur when vaccination of puppies is delayed or incomplete. Shedding of modified viruses and high stability outside the host have been responsible for inadvertent immunization of many dogs. Vaccines for ICH contain either a killed homologous canine adenovirus-l (CAV-l) or a closely related respiratory isolate, MLV canine adenovirus-2 (CAV-2). The former is generally shed in the urine, and the latter is shed in upper respiratory secretions; however, the amount that is shed varies between individual products. Another side effect of attenuated CAV-l vaccine is its ability to produce anterior uveitis and corneal edema with opacification ("blue eye") in a small percentage of dogs. It is not documented that CAV-2 vaccines cause uveitis. Although inactivated vaccines produce a lesser serologic response, they are not shed by the host, nor do they cause anterior uveitis. In the absence of exposure to virulent virus, periodic boosters of inactivated adenovirus vaccine might be required to sustain immunity. The half-life of maternal antibody to ICH is similar to that of COY: approximately 8.5 days. By the time a puppy reaches 14 to 16 weeks of age, maternal antibody is not usually detectable. Vaccination for ICH is thus typically combined with that for CDV. The initial vaccines can be administered when puppies are 6 to 8 weeks of age and every 3 to 4 weeks until they reach 16 weeks of age. Although booster inoculation is recommended annually in adult dogs, challenge studies have demonstrated that the duration of immunity is at least 7 years when attenuated CAV-2 is used as the vaccine antigen. 29 The duration of immunity of killed CAV-2 vaccine and the MLV CAV-2 (intranasal) is not known. MLV CAV-2 has been shown to immunize dogs against the respiratory (CAV-2) and hepatic (CAV-l) adenoviruses. Considering the risks associated with administration of CAV-l to dogs, the use of the MLV CAV-l vaccine is not recommended. Infectious tracheobronchitis (ITB), or kennel cough, is a complex clinical infection caused by a number of respiratory pathogens that can infect dogs alone or in combination. Causative viruses include distemper (CDV), adenovirus (CAV-2), parainfluenza virus, herpesvirus, and Reovirus. Bordetella bronchiseptica is a recognized bacterial pathogen. 4 ,13 Secretory antibody (not that in serum) provides protection against infections of the upper respiratory mucosal surfaces. Parenteral and intranasal vaccines exist for CAV-2, parainfluenza virus, and B. bronchiseptica. Although protection against most agents develops after routine vaccination programs, vaccines against some agents such as herpesvirus or Reovirus are not available. The duration of immunity produced by many vaccines against respiratory pathogens has not been well established, but the labels of most products recommend annual boosters. It is unlikely that dogs derive significant immunity beyond 12 months subsequent to intranasal vaccination. For intranasal B, bronchiseptica vaccine, the duration of immunity may actually be less than 12 months. The performance of parenterally administered infectious tracheobronchitis (ITB) vaccines is quite different from that of intranasally (topically) administered vaccine. Parenterally administered vaccine for ITB provides a duration of immunity of up to 7 months or longer depending on the antigen?' 29 It is not known whether parenteral administration of ITB antigens culminates in the development of an effective local (upper respiratory tract) immune response. Maternal antibody interferes with parenterally administered vaccine. On the other hand, vaccine labeled for intranasal (topical) administration can be administered in puppies as young as 3 weeks of age (depending on the product), seems to induce a local immune response that is not interfered with by maternal antibody, and has a relatively rapid onset (3-5 days). It should be noted that although pneumonia caused by virulent B. bronchiseptica CANINE VACCINATION 483 has been reported in immunocompromised human beings, inadvertent nasal or ocular exposure to avirulent live canine B. bronchiseptica vaccine is not known to have caused clinical illness or symptoms in human beings. Vaccination with separate parenteral products usually begins in puppies at 6 weeks of age and is safe for pregnant animals. Animals should receive at least two doses 2 to 4 weeks apart, and complete protection is not expected until 2 to 3 weeks after the second vaccination. Intranasal parainfluenza and Bordetella vaccines may protect within 72 hours after their use; thus, they can be used to help prevent illness in an outbreak in a kennel or in pets before hospitalization or boardingP Vaccination against respiratory pathogens does not induce sterile immunity. In other words, vaccinated animals that are challenged are expected to become infected and may exhibit a mild short clinical illness. Clinical signs of upper respiratory infection may develop subsequent to intranasal administration of vaccine. Signs are generally mild or unnoticeable. Canine parvovirus-2 (CPV-2) vaccines are available as inactivated or MLV products. Recombinant vaccines are not currently available but are being developed. MLV products offer faster, more effective protection against disease and shedding of virulent virus after challenge than inactivated vaccines. For this reason, older dogs that are housed with younger susceptible animals should be vaccinated with MLV vaccines. In case of an outbreak, MLV vaccines should always be used. MLV CPV-2 products are consistently shed in the feces of vaccinated dogs. Infected contact animals may develop weak positive reactions on fecal parvovirus enzyme-linked immunosorbent assay (ELISA) tests but will not develop disease. Maternal antibody blockade is the predominant reason that parvoviral vaccination is inconsistent in protecting pups during their primary vaccination series.1O,16 Attenuated or inactivated vaccines do not break through maternal immunity as effectively as virulent canine parvovirus. To overcome the period of maternal antibody blockade, manufacturers have raised the titers or lowered their serial passage. 8 ,28.29 Recommendations for use of these potent parvoviral vaccines are a complete series beginning at 6 weeks of age. Repeat vaccines are given every 3 to 4 weeks until dogs are 16 weeks old despite the fact that some products have label claims of protection by 12 weeks of age. The last inoculation should be given at 16 weeks of age for breeds such as Doberman Pinschers and Rottweilers, which have been identified as being poorly responsive to CPV vaccination. In the absence of maternal immunity, where pups are presented after 16 weeks of age, one MLV CPV-2 inoculation may be sufficient for protection against parvoviral infection. Vaccination with MLV CDV with concurrent CPV-2 vaccination does not cause immunosuppression as has been observed in coinfection with virulent CPV-2 virus. Alternating between distemper and parvoviral vaccines in young puppies on a weekly or longer interval is thus not needed or recommended. If an animal recovers from a documented parvoviral infection, it is recommended to wait 4 weeks before vaccinating it so that the immune response is recovered. Immunity to parvoviral infection is probably lifelong; however, boosters are given because of the convenience afforded by combination products. Because of the great environmental resistance of parvoviruses, young pups should be kept away from parks, boarding facilities, and dog shows until the vaccination series is complete. Veterinarians should attempt to limit suspected parvovirus-infected dogs from coming into contact with susceptible puppies in their veterinary hospital waiting rooms and wards. Vaccination of cats against feline panleukopenia protects them against CPV-2b infection. There has been a genetic and resultant antigenic shift of canine parvovirus since its initial evolution in 1978. Nevertheless, cross-protection still exists between the old CPV-2 strains in the vaccine and the new field isolates (CPV-2a and CPV-2b). Similarly, immunodiagnostic tests based on monoclonal antibodies to original isolates are still sensitive in detecting newer strains of virus. Newer field isolates can infect cats. There is limited evidence to suggest that vaccines based on 2b strains do not infect cats. Duration of immunity of MLV CPV-2 vaccines is several years (at least 7 years based on challenge studies),29 and overvaccination is a consideration. The duration of immunity subsequent to administration of inactivated (killed) CPV products has been shown to protect puppies from challenge for at least 16 months after vaccination.25 Under field conditions, dogs may be partially protected by weaker MLV or inactivated products yet still boost their immunity when exposed to virulent virus. Most vaccines licensed for canine coronavirus (CCV) are inactivated canine coronaviral or feline coronaviral strains. One attenuated (MLV) canine coronaviral product exists. Manufacturers recommend that two doses of vaccine be given 2 to 3 weeks apart beginning in puppies at 6 to 8 weeks of age, with the last one being given at least after 12 weeks of age. The vaccines seem to be safe; however, allergic reactions may occur more commonly when inactivated corona viral vaccines are com-bined with leptospiral bacterins. To avoid potential interactions, CCV vaccine could be used in puppies between 6 and 9 weeks of age, and Leptospira vaccination could be instituted thereafter. Otherwise, the clinician may prefer to decide whether or not it is important or necessary that both products be administered. CCV challenge studies are not indicative of "protection" since it is not possible to produce experimental disease in dogs over 12 weeks of age. Furthermore, manufacturer recommendations to administer CCV booster vaccines annually are difficult to justify based on the fact that CCV does not cause disease in adult dogs. CCV produces significantly less morbidity and minimal mortality compared with CPV-2. Experimentally, combined infections with CPV-2 and CCV have been shown to produce clinical disease that is more severe than with either infection alone. 1 Nevertheless, it has also been shown that vaccination with CPV can prevent clinical disease when both viruses are present.1 9 ,28 The routine and frequent use of CCV vaccine in dogs is difficult to rationalize. Clinical infection typically occurs in puppies 6 weeks of age or younger. Some studies have suggested that the duration and quality of immunity derived from natural exposure and infection are actually preferred over attempts to immunize by way of vaccination. 28 In the absence of reliable commercial or in-hospital diagnostic assays for CCV, the prevalence of clinical disease associated with CCV infection in dogs is unknown but is considered to be extremely low, even in high-density shelter environments. Yet CCV, both killed and MLV, is commercially incorporated into several multivalent vaccines combined with distemper, adenovirus, parainfluenza virus, and parvovirus antigens. The fact that multivalent vaccines containing CCV outsell vaccines that do not contain CCV in the United States suggests that routine CCV inoculation of dogs throughout life is common. CCV vaccine is considered to be among the least important vaccine antigens given to dogs today, however, and has been identified by several authors as a vaccine that, quite simply, is not needed. 9 ,28 Most leptospiral vaccines for dogs contain inactivated serovars of canicola and icterohaemorrhagiae. Vaccination with these products is not recommended in animals less than 9 weeks of age because of the allergenic nature of these products. Leptospira bacterin is usually used to reconstitute the lyophilized components in combination vaccines. Leptospira bacterins may not produce as high a level or as long a duration of immunity as other agents. Although postvaccination titers often decline to undetectable levels, unpublished challenge studies suggest that immu-nity in some dogs is sustained for 1 year. Inactivated Leptospira vaccines may not, however, protect against the carrier state that may develop after exposure to virulent organisms. One vaccine manufacturer has employed a technology that involves separating surface proteins, or immunogens, of Leptospira from extraneous cellular debris, thereby avoiding the need to use whole-cell bacteria. It is not known whether or not this technology can reduce the incidence of adverse events in young dogs and toy breeds over that recognized with conventional wholecell bacterins. Leptospiral vaccines have been considered optional by veterinarians in many areas because of the perceived low incidence of the disease, short duration of immunity, and risk of postvaccinal hypersensitivity. The use of Leptospira vaccine is probably responsible for the reduced prevalence of disease caused by L. canicola and L. icterohaemorrhagiae. Recently, it has been shown that the incidence of confirmed cases of canine leptospirosis may be increasing in the United States. S ,33 Furthermore, dogs are being diagnosed with infections by serovars of L. interrogans that we do not routinely vaccinate against. Serovars of L. grippotyphosa, L. pomona, L. bratislava, and others are reported throughout the United States and have been linked to acute renal failure. 6 ,33 Another interesting point is that many of these reports are on dogs living exclusively in urban areas. The risk of infection is not limited to dogs living outdoors in rural environments. Vaccines containing conventionally used serovars of L. canicola and L. icterohaemorrhagiae do not cross-protect against other serovars known to infect dogs. s Less than 2 years ago, Leptospira vaccines were introduced that are believed to protect against serovars L. grippotyphosa and L. pomona. Additional Leptospira serovars are likely to be introduced in the near future. Nevertheless, the incidence of acute anaphylaxis among young dogs (especially those under 12 weeks of age) and toy breeds (regardless of age) makes the decision to include routine vaccination of dogs with all available Leptospira serovars difficult. Without regional incidence data for canine leptospirosis, practitioners still have insufficient information at their disposal to make a reasonable riskbenefit analysis regarding use of leptospira vaccines. Commercial inactivated (killed) whole-cell bacterins and one recombinant outer surface protein A (OspA) vaccine is licensed in the United States. 14 ,26 In Europe, the vaccines are of the whole-cell type. Vaccines have been shown by challenge studies conducted by the manufacturer of the recombinant outer surface protein A vaccine to provide a duration of immunity for up to 1 year. Vaccination protected challenged dogs from spirochetemia and clinical limping episodes as compared with unvaccinated dogs. Lyme borreliosis vaccines are recommended by the manufacturer for use in dogs as young as 9 to 12 weeks of age, and primary vaccination consists of two inoculations 3 weeks apart. Immunization should be given early in life to high-risk dogs living in endemic regions. It should be noted that all vaccines stimulate antibody that produces a positive test result with the indirect fluorescent antibody serodiagnostic test. Dogs having a positive indirect fluorescent antibody test should be retested using either of two tests: the Western blot technique, which may discriminate between infection and vaccine-induced antibody, or the recently introduced in-hospital ELISA test (SNAP 3Dx Assay; IDEXX Laboratories, Westbrook, ME), which has been shown to react only to antibody from a unique C6 surface peptide. 21 The ELISA test does not cross-react to antibody produced by any of the commercially available vaccines on the market in the United States. Claims of hypersensitivity induced by whole-cell Lyme vaccines have been reported. The most common observation is postvaccination lameness among dogs that did not show clinical or serologic evidence of infection. Unfortunately, the vaccines contain a limited number of strains, which may not cross-protect against the known isolates of B. burgdorjeri. Routine testing of dogs using the in-hospital ELISA test in regions of the United States where Lyme borreliosis is suspected or is known to occur in human beings can provide new information pertaining to the regional incidence of infection among the canine population. Today, that information is largely extrapolated from human incidence data maintained by the Centers for Disease Control and Prevention. In the meantime, routine vaccination of dogs against B. burgdorjeri is not indicated outside regions of known high disease prevalence. Infection with the protozoan Giardia lamblia is known to affect mammals and birds worldwide. Differences exist in the pathogenicity and host range of various strains. Colonization of the intestinal lumen results in intestinal villus shortening and malabsorptive diarrhea. Neonatal animals are most susceptible to infection. 3 Areas with impounded unfiltered surface water that is used for recreation or drinking are most often associated with infection. Unsanitary conditions can lead to endemic infections. An inactivated adjuvanted vaccine is available for vaccination of puppies and kittens. The first dose can be given in animals as young as 8 weeks of age. Neither routine or annual revaccination is indicated .;:. 00 00 with this product, except in the unusual situation where recurrent exposure and infection are documented and cannot be controlled using conventional hygienic methods. This vaccine has been shown to diminish fecal shedding of the infectious cysts for up to 1 year. The vaccine also reduces the rate and quantity of infection when given before exposure. If the prevalence of infection is high in a group of animals or in a specific area, this vaccine might be an adjunct to help control the disease. It is not recommended for administration to all dogs, and its use must be coupled with other management procedures. The current vaccine has been shown to cause granuloma-like masses at the inoculation site. It is important to note that accurate identification of Giardia in dogs with diarrhea is not as straightforward as it may seem. As such, falsepositive diagnoses of giardiasis are probably common. Conventional saline fecal flotation techniques are not adequate to diagnose Giardia cysts in feces. Furthermore, direct fecal examination is limited by the experience of the microscopist and by the fact that many other structures in the feces of dogs such as yeast bodies are easily confused with Giardia cysts. Feces should be subjected to centrifugal flotation in a 33% zinc sulfate solution. The slide should be scanned with a X 10 objective magnification. Rabies vaccines have been extremely effective in reducing the prevalence of this disease in dogs. As a result, the prevalence of human disease has decreased substantially, although the relative prevalence of feline rabies has increased in the United States. In most countries, inactivated (killed) vaccines are used. Inactivated virus vaccines have been shown to provide a minimum duration and level of immunity comparable to those of MLV products. They often contain high viral content and potent adjuvants, however, which can sometimes produce acute or chronic hypersensitivity reactions. An avipoxvirus-vectored recombinant rabies vaccine that produces minimal inflammatory reactions has been licensed for use in cats. 31 A single rabies vaccine is generally administered in animals 3 to 4 months of age. A second dose should be administered 1 year after the first dose regardless of the dog's age. Subsequent boosters are required every 1 or 3 years thereafter as mandated by state law or local statutes. New technologies for vaccine development ll , 32 and infectious disease diagnosis21 are likely to be introduced in the near future. With this new technology comes the opportunity to vaccinate companion animals against even more infectious agents than is currently practiced in the United States today. As we look forward, it become;,> particularly important to review current vaccination standards applied to dogs with respect to current knowledge of duration of immunity (Table 2) , awareness of the incidence and likelihood of injurious or even fatal adverse events associated with vaccination, and individual risk factors that dictate which vaccines are most appropriate at which stage of life. Does canine coronavirus augment the effects of subsequent parvovirus infection Canine distemper virus Giardiasis in dogs and cats Viruses recovered from laboratory dogs with respiratory disease Diagnosis of leptospirosis: A reemerging disease of companion animals Leptospira interrogans serovar grippotyphosa infection in dogs Duration of Immunity in Companion Animals after Natural Infection and Vaccination Performance of a high titre attenuated canine parvovirus vaccine I in pups with maternally derived antibody Canine viral vaccines at a turning point-a personal perspective Vaccines for dogs DNA vaccines Vaccine-induced immune-mediated hemolytic anemia in the dog Canine infectious tracheobronchitis Humoral immune response of dogs after vaccination against Leptospirosis measured by an IgM and 19E specific ELISA Vaccine-induced autoimmunity in the dog Effect of maternally derived antibody levels on antibody responses to canine parvovirus, canine distemper virus and infectious canine hepatitis virus after vaccinations in beagle puppies Canine infectious tracheobronchitis: Effects of an intranasal live canine parainfluenza-Bordetella bronchiseptica vaccine on viral shedding and clinical tracheobronchitis (kennel cough) Comparison of selected canine vaccines for their ability to induce protective immunity against canine parvovirus infection Efficacy of immunity induced by canine coronavirus (CCV) vaccines compared against immunity after natural infection with CCV High-titer canine parvovirus vaccine: Serologic response and challenge-of-immunity study Characterization of a Borrelia burgdorferi VIsE invariable region useful in canine Lyme disease serodiagnosis by enzyme-linked immunosorbent assay State of the art: Bacterial vaccines Protection of dogs against canine distemper by vaccination with a canary pox virus recombinant expressing virus fusion and hemagglutinin glycoproteins State of the art: Viral vaccines [abstract) The duration of immunity to an inactivated adjuvanted canine parvovirus vaccine Efficacy of a nonadjuvanted, outer surface protein A recombinant vaccine in dogs after challenge by ticks naturally infected with Borrelia burgdorferi Report of the American Association of Feline Practitioners and Academy of Feline Medicine Advisory Panel on Feline Vaccines Current and future canine and feline vaccination programs Duration of immunity to canine vaccines: What we know and don't know Rabies vaccines: Duration of immunity study in dogs Rabies vaccines. In Rabies: Guidelines for Medical Professionals Genetic vaccines Canine leptospirosis Challenge studies required *The duration of immunity listed for individual antigens represents the length of time dogs were followed before challenge or before measuring antibody; it does represent the maximum possible duration of immunity.Although a modified-live canine adenovirus-l vaccine is still available at this writing, use of this product in clinical practice is not recommended.