DLA class II alleles and haplotypes are associated with risk for and protection from chronic hepatitis in the English Springer spaniel.

Chronic hepatitis (CH) is common in dogs in the United Kingdom. An increased prevalence of the disease is seen in the English Springer spaniel (ESS), and this breed suffer from a severe form with young to middle aged female dogs being predisposed. The disease shares histological features with those of human viral hepatitis, although the specific aetiological agent has not yet been identified. The aim of the current study was to investigate whether dog leucocyte antigen (DLA) class II alleles and haplotypes are associated with susceptibility/resistance to CH in the ESS. Sequence-based genotyping of the polymorphic exon 2 from DLA-DRB1, -DQA1 and -DQB1 class II loci were performed in 66 ESSs with CH and 84 healthy controls. There was a significant difference in the distribution of the protective alleles DRB1*00501 (3.0% vs. 12.0%, odds ratio [OR] = 0.23, 95% confidence interval [CI] = 0.06-0.74) and DQB1*00501 (3.8% vs. 12.0%, OR = 0.29, 95% CI = 0.09-0.85) between cases and controls. The haplotype DLA-DRB1*00501/DQA1*00301/DQB1*00501 was present in 11.9% of controls and 3.0% of cases and was significantly associated with protection against disease development (OR = 0.26, 95% CI = 0.08-0.80). There was a significant difference in the distribution of the risk alleles DRB1*00601 (14.4% vs. 6.5%, OR = 2.40, 95% CI = 1.10-5.63) and DQB1*00701 (14.4% vs. 6.5%, OR = 2.40, 95% CI = 1.10-5.63) between cases and controls. A risk haplotype (DLA-DRB1*00601/DQA1*005011/DQB1*00701) was present in 14.4% of cases and 6.5% of controls and conferred an elevated risk of developing CH with an OR of 3.13 (95% CI = 1.20-8.26). These results demonstrate that DLA class II is significantly associated with risk and protection from developing CH in ESSs.

Augmented induction of antigen-specific cytotoxic T cell responses against canine hepatitis by co-immunization with pVAX1-CpG-Loop and adjuvants in BALB/c mice.

The objective of this study was to obtain better antigen specific cytotoxic T cell responses in vivo. We examined the augmented induction of antigen-specific cytotoxic T cell responses to co-administration of oligonucleotides (CpG-ODN), dimethyl dioctadecyl ammonium bromide (DDA), and Lipofectamine™ 2000 with a DNA vaccine (pVAX1-CpG-Loop) and boosting with pVAX1-CpG-Loop in BALB/c mice. The results show that Loop protein-specific T cell proliferation, cytotoxic T cell activity, and the production of CD8+ T cells and IFN-γ were enhanced after co-immunization of mice with adjuvants and pVAX1-CpG-Loop. We demonstrated that significant T cell-mediated immune responses were induced in the mice with the help of DDA, CpG-ODN and Lipofectamine™ 2000.

Safety evaluation of a canine hepatitis DNA vaccine.

DNA vaccines are a novel disease prevention methodology, however their safety has not been well described. We evaluated the safety and efficacy of the DNA vaccine pVAX1-CpG-Loop against infectious canine hepatitis. We demonstrated that pVAX1-CpG-Loop could not be recovered from tissues of vaccinated mice nor from F1 progeny and following vaccination there were no apparent changes in hematologic markers compared to unvaccinated controls. Most important, vaccinated mice were protected from viral challenge. The only detectable effects of the vaccination were elevated AST levels 4 weeks post vaccination and liver lymphocyte infiltration and hydropic degeneration which normalized 6 months later.

Augmented humoral and cellular immune responses induced by canine adenovirus type 1 DNA vaccine in BALB/c mice.

Infectious canine hepatitis (ICH) is caused by canine adenovirus type 1 (CAV-1), which severely harms infected animals. Vaccination provides an effective approach to preventing canine infectious diseases. With the objective of exploring a new vaccination strategy that may prevent or cure ICH, we constructed a DNA vaccine, pVAX1-CpG-Loop, and evaluated its immune efficacy. We found that vaccination of BALB/c mice with the DNA vaccine alone, or priming with DNA vaccine and boosting with the Loop protein, resulted in the following: (1) High-level specific antibody (IgG) against CAV-1 was induced; (2) T cell activation was elicited; and (3) neutralizing antibodies were detectable in immunized mice. Collectively, these data indicate that the availability of a DNA vaccine could prevent hepatitis contagiosa canis.

Canine parvovirus infection, canine distemper and infectious canine hepatitis: inclination to vaccinate and antibody response in the Swedish dog population.

The inclination of dog owners to vaccinate was investigated by sending a questionnaire to randomly selected Swedish dog-owning households. According to the owners (n = 538), 86.7% of the dogs had been vaccinated against CPV and 95.8% had been vaccinated against CD/ICH. The inclination to vaccinate mixed breeds was significantly lower than the inclination to vaccinate pure-bred dogs. In a second study titres of CPV, CD and CAV-1 virus antibodies were measured in 176 randomly selected dogs with known vaccination histories. CPV antibody titres > or = 1:80 were detected in 70.9% of the CPV vaccinated dogs. There was a significant difference in the fraction of dogs with CPV titre > or = 1:80 between the group last vaccinated with live attenuated vaccine and the group last vaccinated with inactivated vaccine. Titres of CD and CAV-1 virus antibodies > or = 1:16 were found in 86.1% and 91.6% of the vaccinated dogs respectively. The fraction of dogs with CAV-1 antibody titres > or = 1:16 was significantly greater in the group that received inactivated CAV-1 vaccine than in the group vaccinated with attenuated live CAV-2 vaccine. Approximately 50% of the dogs were booster vaccinated against all 3 diseases at one year of age.

[Hepatitis contagiosa canis (H.c.c.)--2 cases in Austria]. / Hepatitis contagiosa canis (H.c.c.)--2 Fälle in Osterreich.

Two cases of H.c.c. which occurred in winter 1987 in Vienna are described. Case one was a female Chow-Chow, 8 weeks of age, that died from the peracute form of the disease. The diagnosis was confirmed by histology and direct immunofluorescence. Case two, a 9-month old female Kuvacz, showed clinical signs of the subacute form of H.c.c. She was hospitalized and therapy was successful. The disease was diagnosed by the typical clinical signs and the raise of antibodies in paired serum samples. Etiology, clinical signs and immunology of H.c.c. are discussed.

Serological survey for selected diseases in the endangered San Joaquin kit fox (Vulpes macrotis mutica).

Blood from endangered San Joaquin kit foxes (Vulpes macrotis mutica) inhabiting the Elk Hills Naval Petroleum Reserve, Kern County, and the Elkhorn Plain, San Luis Obispo County, California, was collected in 1981, 1982 and 1984 and sera were tested for antibodies against 10 selected pathogens. Proportions of kit fox sera containing antibodies against pathogens were: canine parvovirus, 100% in 1981-1982 and 67% in 1984; infectious canine hepatitis virus, 6% in 1981-1982 and 21% in 1984; canine distemper virus, none in 1981-1982 and 14% in 1984; Francisella tularensis, 8% in 1981-1982 and 31% in 1984; Brucella abortus, 8% in 1981-1982 and 3% in 1984; Brucella canis, 14% in 1981-1982 and none in 1984; Toxoplasma gondii, 6% in 1981-1982; Coccidioides immitis, 3% in 1981-1982; and Yersinia pestis and Leptospira interrogans serotypes canicola, grippotyphosa, hardjo, icterohaemorrhagiae, and pomona, none in 1981-1982. Although antibodies against selected pathogens were present, no clinical indications of disease were observed in these fox populations.

Viral-antibody complexes in canine adenovirus type 1 (CAV-1)ocular lesions: leukocyte chemotaxis and enzyme release.

Canine adenovirus-type 1 (CAV-1)-antibody complexes caused severe anterior uveitis with corneal edema ("blue eye") when injected into the anterior chamber of normal dogs. The response of the anterior uvea to such immune complexes (IC) was similar to the spontaneously occurring disease. In the presence of complement (C'), IC caused release of neutrophile chemotactic factors. Following phagocytosis of IC-C' leukocytes released lysosomal enzymes, as indicated by the presence of acid phosphatase in the surrounding medium. Membrane bound viral aggregates, presumably IC, were common in neutrophiles and in macrophages that had infiltrated the anterior chamber of opaque eyes that occurred after intravenous (IV) inoculation with attenuated CAV-1. These data were incorporated into a postulated scheme for the pathogenesis of CAV-1 uveitis with corneal edema.

Glomerular deposition of immune complexes in dogs following natural infection with canine adenovirus.

The renal lesions were studied in eight dogs which had either died as a result of acute canine adenovirus infection (Rubarth's disease) or were in various stages of recovery from the clinical disease. Using immunofluorescence techniques granular deposits of IgG were detected in the glomeruli of six dogs; four of these animals had similar glomerular deposits of canine adenovirus antigen. Eluates obtained from kidney tissue of four dogs were found to contain antiviral antibody. Histologically those animals in which glomerular deposits of IgG and viral antigen were detected showed segmental glomerular hypercellularity. These findings were attributed to the deposition of circulating virus antigen-antibody complexes in the glomeruli.