A modified live canine parvovirus vaccine. II. Immune response

The safety and efficacy of an attenuated canine parvovirus (A-CPV) vaccine was evaluated in both experimental and in field dogs. After parenteral vaccination, seronegative dogs developed hemagglutination-inhibition (HI) antibody titers as early as postvaccination (PV) day 2. Maximal titers occurred within 1 week. Immunity was associated with the persistence of HI antibody titers (titers greater than 80) that endured at least 2 years. Immune dogs challenged with virulent CPV did not shed virus in their feces. The A-CPV vaccine did not cause illness alone or in combination with living canine distemper (CD) and canine adenovirus type-2 (CAV-2) vaccines, nor did it interfere with the immune response to the other viruses. A high rate (greater than 98%) of immunity was engendered in seronegative pups. In contrast, maternal antibody interfered with the active immune response to the A-CPV. More than 95% of the dogs with HI titers less than 10 responded to the vaccine, but only 50% responded when titers were approximately 20. No animal with a titer greater than 80 at the time of vaccination became actively immunized. Susceptibility to virulent CPV during that period when maternal antibody no longer protects against infection, but still prevents active immunization, is the principal cause of vaccinal failure in breeding kennels where CPV is present. Reduction, but not complete elimination, of CPV disease in large breeding kennels occurred within 1-2 months of instituting an A-CPV vaccination program.     

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

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

Viral antibody studies of laboratory dogs with diarrheal disease

Viral antibody studies were done on laboratory dogs in an epizootic of gastrointestinal disease. Increased hemagglutination-inhibition antibody titers to a parvovirus (PV) antigenically related to feline panleukopenia virus were found in convalescent serum specimens of 78% (20/26) of the affected dogs and in 83% (5/6) of apparently healthy dogs. With one exception, all dogs tested had significant levels of hemagglutination-inhibition antibody to this PV. Similar increased antibody titers were found to feline panleukopenia virus. Also, neutralizing antibody responses were detected to the canine coronavirus in 24% (6/25) and canine herpesvirus in 45% (10/22) of the affected dogs. However, antibody titers did not increase to canine distemper virus, infectious canine hepatitis virus, canine parainfluenza virus, or minute virus of canines. Subsequent serotesting of the colony provided evidence that additional PV infections occurred in pups from each of 8 litters born 3 to 8 months after the epizootic. These findings indicated the continued presence of the PV for more than 1 year in the infected colony. Of 19 laboratory personnel who worked with the affected dogs, none, including 4 with a concurrent diarrheal disease, developed or had antibodies to the PV or canine coronavirus.     

Evaluation of antithyroglobulin antibodies after routine vaccination in pet and research dogs

OBJECTIVE: To determine whether routine vaccination induces antibodies against bovine thyroglobulin and autoantibodies against canine thyroglobulin in dogs. DESIGN: Prospective study. ANIMALS: 20 healthy research Beagles and 16 healthy pet dogs. PROCEDURE: For the research Beagles, 5 dogs were vaccinated with a multivalent vaccine and a rabies vaccine, 5 dogs received only the multivalent vaccine, 5 dogs received only the rabies vaccine, and 5 dogs were unvaccinated controls. The multivalent vaccine was administered at 8, 10, 12, 16, 20, 26, and 52 weeks of age and every 6 months thereafter. The rabies vaccine was administered at 16 and 52 weeks of age and then once per year. Blood was collected from all dogs at 8, 16, and 26 weeks of age and then 4 times yearly. Assays for antibodies directed against bovine and canine thyroglobulin were performed prior to and 2 weeks after each yearly vaccination. For the pet dogs, blood was collected prior to and 2 weeks after 1 vaccination. RESULTS: In the research Beagles, there was a significant increase in anti-bovine thyroglobulin antibodies in all vaccinated dogs, compared with control dogs. There was a significant increase in anti-canine thyroglobulin antibodies in the 2 groups of dogs that received the rabies vaccine but not in the group that received the multivalent vaccine alone. In the pet dogs, there was a significant increase in anti-canine thyroglobulin antibodies after vaccination but no significant change in anti-bovine thyroglobulin antibodies. CONCLUSIONS AND CLINICAL RELEVANCE: Recent vaccination may result in increased anti-canine thyroglobulin antibodies. Whether these antibodies have a deleterious effect on canine thyroid function is unknown.     

Chronological analysis of canine parvovirus type 2 isolates in Japan

Fifty-five canine parvovirus type 2 (CPV) samples, 12 fecal specimens and 43 cell culture isolates, were examined for their genetic characteristics of VP2 gene. They were collected from the diseased dogs at various districts of Japan during 27 years from 1980 to 2006. A fragment of VP2 gene was analyzed by restriction fragment length polymorphism assay and DNA sequencing. The original antigenic type 2 of CPV (CPV-2) was no longer found in the samples since 1984, and two antigenic variants CPV-2a and CPV-2b replaced CPV-2 as predominant types for about 5 years from 1982. A new genetic variant of prototype CPV-2a with non-synonymous substitution at the VP2 amino acid residue 297 from Ser to Ala was first detected in 1987. New CPV-2b with the same amino acid substitution at position 297 as new CPV-2a was also detected from the samples collected in 1997. Since then new CPV-2b has been the predominant CPV over the field of Japan. Several additional amino acid substitutions were detected in the VP2 gene of some recent CPV strains. Neither CPV-2c(a), CPV-2c(b), nor "Glu-426" of the antigenic variants previously found outside the country was detected in any samples tested. Reactivity of new CPV-2a and 2b variants against antibodies produced by the current vaccine products was determined by a cross hemagglutination-inhibition test. The recent field CPV isolates reacted more efficiently to the antibodies produced in dogs vaccinated with the new CPV-2b vaccine strain than the conventional CPV-2 vaccine strain.     

The seroprevalence of canine parvovirus-2 in a selected sample of the canine population in ontario

Canine sera, collected from dogs presented to the Ontario Veterinary College between 1976 and 1980, were assessed for canine parvovirus-2 antibody using a microtitre hemagglutination-inhibition test. Special emphasis was made on the period from September 1979 to October 1980 (2892 samples). No antibody was detected in samples collected in 1976 or 1977. The first positive sera were obtained in January 1978. By the end of 1978 antibodies to canine parvovirus-2 were widespread in Ontario dogs and in 1980, 683 of 2191 dogs (31.2%) had antibody. This was before widespread vaccination was being practised and indicates canine parvovirus-2 infection occurred frequently. Evaluation of clinical records of these dogs suggested that most infections had been subclinical.     

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

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

Evaluation of a novel tumor vaccine in dogs with hemangiosarcoma

BACKGROUND: Hemangiosarcoma (HSA) is a highly metastatic and often rapidly fatal tumor of dogs. At present, adjuvant chemotherapy is the only proven effective treatment for dogs with HSA, though the benefits from chemotherapy are modest. Administration of immunotherapy together with chemotherapy has also been reported to improve survival in dogs with HSA. Therefore, we evaluated safety and immunologic responses to a novel tumor vaccine administered together with doxorubicin chemotherapy in dogs with different stages of HSA. HYPOTHESIS: That tumor vaccination could be safely and effectively combined with doxorubicin chemotherapy for treatment of dogs with HSA. ANIMALS: Twenty-eight dogs with various stages of HSA were enrolled in the study. METHODS: The HSA vaccine was prepared with lysates of allogeneic canine HSA cell lines mixed with an adjuvant composed of liposome-DNA complexes. Dogs received a series of 8 immunizations administered over a 22-week period, and most also received chemotherapy. Clinical adverse effects were noted, immune responses were measured by enzyme-linked immunosorbent assay (ELISA) and flow cytometry, and survival times were calculated. RESULTS: The most common adverse effects observed in vaccinated dogs also treated with doxorubicin chemotherapy were diarrhea and anorexia. Vaccinated dogs were found to mount strong humoral immune responses against a control antigen and, most dogs also mounted antibody responses against canine HSA cells. Thirteen dogs with stage II splenic HSA that received the tumor vaccine plus doxorubicin chemotherapy had an overall median survival time of 182 days. CONCLUSIONS: We conclude that an allogeneic tumor lysate vaccine is safe in dogs with HSA and can elicit humoral immune responses in dogs that are receiving concurrent doxorubicin chemotherapy.     

Seroprevalence of canine parvovirus in wild coyotes from Texas, Utah, and Idaho (1972 to 1983)

The prevalence of serum antibodies against canine parvovirus-2 (CPV-2), as measured by a standard hemagglutination-inhibition test, was determined in serum samples collected from 1,184 coyotes (Canis latrans) in Texas, Utah, and Idaho from 1972 to 1983. No evidence of parvoviral infection was found before 1979, after which seroprevalence rapidly increased to greater than 70% at all sites by 1982. There were minor differences in prevalence between age groups and among sites, but no consistent differences between sexes. The onset of CPV-2 seroprevalence in free-ranging coyotes coincided remarkably with the recognition of the clinical disease and seroprevalence in domestic dogs in the United States.     

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

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

The immune response to disialoganglioside GD3 vaccination in normal dogs: a melanoma surface antigen vaccine

As a result of its metastatic potential, canine malignant melanoma like its human counterpart like its human counter part, has a poor response to conventional treatment protocols. This prompted us to investigate the possibility of enhancing the immune response against the melanoma cell surface antigen, disialoganglioside GD3. Initially a flow cytometric study was designed in which the incidence of GD3 on the cell surface, recognized by the monoclonal antibody Mel-1 (R24), was established in canine melanoma cell lines. Results from the flow cytometry found GD3 to be highly expressed (94.2%) in six out of seven canine melanoma cell lines. Since it was thus potentially a good target, a study in which normal dogs were vaccinated intradermally with a vaccine containing GD3 plus adjuvants was designed. The adjuvant included CpG oligodeoxynucleotide (CpG-ODN) sequences and RIBI-adjuvant, which are known to target toll-like receptors (TLR) of the innate immune system. From a cohort of 10 dogs, 4 were vaccinated 3 times, at 4 weekly intervals with GD3 plus adjuvant, and 4 received only RIBI-adjuvant, and 2 phosphate buffered saline. Caliper measurements were collected to assess skin reaction at the vaccination site and sera assayed for IgM and IgG antibodies against GD3 and cell-mediated cytotoxicity against a melanoma cell line. Results from the study found significant differences (P<0.05) in the vaccine site reactions, IgM/IgG levels and cell-mediated cytotoxicity in the vaccinated versus unvaccinated dogs. The addition of CpG-ODN sequences and increasing GD3 concentration in the vaccine increased the inflammation response at the injection site. GD3 IgG and IgM antibodies in vaccinated dogs showed increasing titers over time and achieved significance at weeks 9 and 12, respectively. Cell-mediated cytotoxicity was only detected in peripheral blood mononuclear cells from vaccinated dogs. In conclusion, by combining the tumor antigen GD3 (a known weak self-antigen) and an adjuvant, tolerance was overcome by an innate and adaptive immune response in this population of normal dogs.     

High-cell-passage canine coronavirus vaccine providing sterilising immunity

OBJECTIVES: To evaluate the ability of a high-cell-passage canine coronavirus vaccine to immunise dogs against challenge with a field isolate of the virus. METHODS: Three dogs that had previously tested seronegative and virus-negative for canine coronavirus were inoculated twice, at 21-day intervals, with the vaccine and kept under observation. Two seronegative and virus-negative dogs served as unvaccinated controls. For safety tests, two additional dogs were inoculated oronasally with 10 times the vaccinal dose and no reactions were observed. Faecal samples were collected daily from the vaccinated dogs after the first and second inoculations. Both vaccinated and control dogs were challenged two weeks after the second vaccination with a field canine coronavirus strain. Blood samples were collected for serological tests before vaccination and at weekly intervals after vaccinations and challenge. RESULTS: Virus was not detected in faecal samples after the first or second vaccinations by virus isolation assays and PCR. Significantly, the vaccinated dogs did not have clinical signs after challenge and no virus shedding was observed. The two unvaccinated control dogs had moderate enteritis, and virus was detected in cell cultures starting from three days postchallenge (dog 1) and two days postchallenge (dog 2), and by PCR for 23 median days. CLINICAL SIGNIFICANCE: This study showed the efficacy of a high-cell-passage canine coronavirus vaccine in preventing infection of dogs by virulent virus and, specifically, its ability to induce sterilising immunity.     

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

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

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

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

Serum antibody response to canine parvovirus, canine adenovirus-1, and canine distemper virus in dogs with known status of immunization: study of dogs in Sweden

Serum antibody titers to canine parvovirus (CPV), canine adenovirus-1 (CAV-1), and canine distemper virus (CDV) were measured in dogs with known immunization status. The dogs represented 3 groups: nonvaccinated dogs less than 12 months old; vaccinated dogs less than 12 months old; and adult dogs greater than 12 months old. For practical reasons, the population from which the specimens were obtained could be considered as free from natural infection with CAV-1 and CDV. In nonvaccinated dogs less than 12 months old, antibodies against all 3 viruses were measured at the time the dogs were given their first vaccination. Altogether, 50.7% of the dogs had titer greater than or equal to 1:10 to CPV, and 26.1 and 46.2% had titer greater than or equal to 1:8 to CAV-1 and CDV, respectively. The concentration of maternal antibody seemed to be of major importance for failure of immunization with use of inactivated CPV vaccine, but not with CAV-1 and CDV vaccination. In dogs less than 12 months old and vaccinated against CPV infection with inactivated virus, only 11.5% had titer greater than or equal to 1:80. In dogs vaccinated against infectious canine hepatitis and canine distemper, 63.2 and 78.3%, respectively, had titer greater than or equal to 1:16. In adult dogs greater than 2 months old and vaccinated against CPV infection, less than 50% had titer greater than or equal to 1:80, regardless of time after vaccination. There was no significant difference in titer between vaccinated and nonvaccinated dogs.(ABSTRACT TRUNCATED AT 250 WORDS)     

Lack of association between repeated vaccination and thyroiditis in laboratory Beagles

BACKGROUND: Intensive vaccination protocols have been suggested as partially responsible for an increased prevalence of autoimmune diseases in dogs in recent years. The aim of this study was to determine whether repeated routine vaccination in dogs is associated with an increased prevalence of thyroiditis. METHODOLOGY/PRINCIPAL FINDINGS: We conducted a prospective experimental study with 20 healthy purpose-bred Beagles. Five dogs were vaccinated with a multivalent vaccine and a rabies vaccine. Five dogs received only the multivalent vaccine, and 5 dogs received only the rabies vaccine. Five dogs were unvaccinated controls. The multivalent vaccine was administered at 8, 10, 12, 16, 20, 26, and 52 weeks of age and every 6 months thereafter. The rabies vaccine was administered at 16 and 52 weeks of age and then once a year. Blood samples were collected 1 week before euthanasia for evaluation of thyroid profiles and measurement of antibodies directed against canine thyroglobulin. Dogs were euthanized at 5.5 years of age, and the thyroid glands were evaluated histopathologically. Thyroiditis was present in 8 of 20 (40%) dogs at postmortem examination. No association was found between a dog being vaccinated and the prevalence of thyroiditis at postmortem examination. However, the power of the study to detect such an association was low because of the unexpected high prevalence of thyroiditis in the unvaccinated control dogs. Thyroid function tests were abnormal in 2 of 8 dogs with thyroiditis but were normal in all dogs without thyroiditis. CONCLUSIONS/SIGNIFICANCE: There was no evidence to support an association between routine vaccination and thyroiditis at postmortem examination in beagle dogs after repeated vaccination.     

Detection of IgM antibodies against a recombinant nucleocapsid protein of canine distemper virus in dog sera using a dot-blot assay

A dot-blot assay for the detection of IgM antibodies (ABs) against canine distemper virus (CDV) in canine serum is described. The diagnostic potential of this technique was evaluated by analysing sera from three test groups: (i) specific pathogen-free (SPF) beagle dogs experimentally infected with virulent CDV; (ii) SPF dogs immunized with a combined vaccine containing CDV, and (iii) SPF dogs immunized with a CDV-free vaccine. As antigen for the dot-blot assay we used the recombinant nucleocapsid protein (N protein) of the virulent A75/17 CDV strain. All 12 dogs of group 1, infected with virulent CDV, showed detectable CDV-specific IgM levels in their serum. All dogs of group 2 were also positive for anti-CDV IgM after the first immunization with the CDV-containing vaccine. The four dogs immunized with a CDV-free vaccine (group iii) remained negative throughout the course of the experiment. From these results, we conclude that the IgM detection test, which requires only a single serum sample, is a useful method for diagnosing current or recent CDV infection in CDV-infected or CDV-immunized dogs under experimental conditions.     

Serological response in broiler chicks to different commercial Newcastle disease and infectious bronchitis vaccines.

Broiler chicks were administered vaccines against Newcastle disease and infectious bronchitis (both Arkansas and Massachusetts strains) at 2 weeks of age as either primary or secondary vaccinations. The vaccine was administered as a spray at 2 weeks of age to chicks that had received Newcastle disease vaccine alone, bronchitis vaccine alone, both vaccines in combination, or no vaccine at day 1 in the hatchery. The Newcastle disease hemagglutination-inhibition response was significantly lower in chicks receiving Newcastle disease vaccine as a secondary vaccine at 2 weeks than in those receiving the vaccine as a primary vaccination at that age. In contrast, the bronchitis hemagglutination-inhibition response was significantly higher in chicks receiving bronchitis vaccine as a secondary vaccination at 2 weeks than in those receiving the vaccine as a primary vaccination at that age.     

犬瘟热的诊断及其预防免疫的研究进展

本文对犬瘟热（CD）的诊断、预防免疫和免疫失败的影响因素及犬瘟热病毒（CDV）的宿主范围进行了综述。CDV不仅感染陆生食肉动物，而且也感染水生食肉动物，并且其宿主范围还在不断扩大。CDV感染主要采用病毒分离、特异性病毒抗原或特异性核酸检测等方法确诊。疫苗包括灭活的CDV疫苗、麻疹病毒（MV）异源苗及CDV弱毒活苗。疫苗接种犬的免疫反应主要取决于毒株特性及犬的应答能力，只有弱毒活苗能诱导产生持久而坚强的保护力。尽管多年来CDV弱毒活苗的使用控制了CD的发生，但最近免疫过的犬发生CD的病例并不少见。分析免疫失败的原因，主要是母源抗体干扰、疫苗质量差、其它病毒的免疫抑制以及CDV流行株可能发生了变异等因素的影响。     

Influence of long-term treatment with tetracycline and niacinamide on antibody production in dogs with discoid lupus erythematosus

OBJECTIVE: To evaluate the effect of long-term treatment with tetracycline and niacinamide on antibody production in dogs by measuring postvaccinal serum concentrations of antibodies against canine parvovirus and canine distemper virus. ANIMALS: 10 dogs receiving long-term treatment with tetracycline and niacinamide (treatment group) and 10 healthy dogs (control group). PROCEDURE: The treatment group included 9 dogs with discoid lupus erythematosus and 1 dog with pemphigus foliaceus on long-term treatment (> 12 months) with tetracycline and niacinamide. The control group included 10 healthy dogs with no clinical signs of disease and no administered medications for the past 3 months. Blood samples were obtained from all dogs by jugular venipuncture. Serum antibody titers against canine parvovirus and canine distemper virus antigens were measured, using hemaglutination inhibition and serum neutralization, respectively, and compared between groups. RESULTS: A significant difference in antibody titers between treatment- and control-group dogs was not found. All dogs had protective antibody titers against canine distemper virus, and 8 of 10 dogs from each group had protective titers against canine parvovirus infection. CONCLUSION AND CLINICAL RELEVANCE: These results provide evidence that long-term treatment with tetracycline and niacinamide does not interfere with routine vaccinations and thus does not seem to influence antibody production in dogs.