Therapeutic Chlamydophila abortus and C. pecorum vaccination transiently reduces bovine mastitis associated with Chlamydophila infection

Abstract

Infections with Chlamydophila abortus and C. pecorum are highly prevalent in cattle and have been associated with bovine mastitis. A prospective cohort study was conducted with a herd of 140 Holstein dairy cows to investigate the influence of Chlamydophila infection on subclinical inflammation of the bovine mammary gland as characterized by somatic cell numbers in milk. PCR detection of C. abortus and low serum antibody levels against Chlamydophila spp. were significantly associated with subclinical mastitis. To examine the effect of the infection by response modification, immune perturbation was done by two subcutaneous administrations of an experimental vaccine preparation of inactivated C. abortus and C. pecorum elementary bodies. Vaccination against Chlamydophila highly significantly decreased milk somatic cell numbers, thus reducing bovine mastitis, and increased antibody levels against Chlamydophila but did not eliminate shedding of C. abortus in milk as detected by PCR. The protective effect peaked at 11 weeks after vaccination and lasted for a total of 14 weeks. Vaccination with the Chlamydophila vaccine, a mock vaccine, or a combination vaccine against bovine viral diseases highly significantly increased C. abortus shedding in milk for 1 week, presumably mediated by the vaccine adjuvant. In summary, this study shows an etiological involvement of the widespread Chlamydophila infections in bovine mastitis, a herd disease of critical importance for the dairy industry. Furthermore, this investigation shows the potential for temporary improvement of chlamydial disease by therapeutic vaccination. Chlamydophila vaccination of cattle might serve as a testing ground for vaccines against human chlamydial infections.

FIG. 1.

Effect of the interaction between day 0 Chlamydophila PCR and anti-Chlamydophila serum IgG1 on milk SCC on days 0 and 12. Chlamydophila PCR-positive cows with low Chlamydophila antibody levels before vaccination have significantly higher somatic cell counts on days 0 and 12 than cows that are Chlamydophila PCR negative and have high anti-Chlamydophila antibody levels (P = 0.001; combined day 0 and 12 data in repeated-measures ANOVA and Tukey HSD test). Data are shown as the antilog of mean log SCC ± 95% confidence interval.

FIG. 2.

Effect of Chlamydophila vaccination on anti-Chlamydophila serum antibodies and milk somatic cell counts. Data are shown as the antilog of mean log SCC ± 95% confidence interval and were normalized for identical day 0 means of Chlamydophila- and mock-vaccinated animals (vaccine on days 0 and 35). A. Chlamydophila-vaccinated cows have significantly higher anti-Chlamydophila serum IgG1 levels than mock-vaccinated cows (P = 0.018; combined time points after day 0 in repeated-measures ANOVA and Tukey HSD test). Levels of anti-Chlamydophila serum IgG1 antibodies are shown as percent optical density in comparison to a low-positive control serum. All cows had positive prevaccination antibody levels. B. Chlamydophila-vaccinated cows have significantly lower milk SCC than mock-vaccinated cows (P = 0.007 for all combined time points after day 0 in repeated-measures ANOVA and Tukey HSD test). Error bars indicate 95% confidence intervals.

FIG. 3.

Effect of Chlamydophila vaccination on milk production and body condition. A. Chlamydophila-vaccinated cows do not produce significantly more milk than mock-vaccinated cows (P = 0.471 for days 44 to 147 in repeated-measures ANOVA). B. Chlamydophila-vaccinated cows tend to have a better body condition on days 70 through 174 than cows that were mock vaccinated, but the difference does not reach statistical significance (P = 0.069 for days 70 to 174 in repeated-measures ANOVA and Tukey HSD test). Error bars indicate 95% confidence intervals.

FIG. 4.

Effect of vaccinations on detection of Chlamydophila in milk. Cows were vaccinated on day 0 with Chlamydophila vaccine or mock vaccine, and all cows on day 104 were vaccinated with a combination of live attenuated IBRV-BRSV-PI3V vaccine and inactivated BVDV vaccine. After both vaccinations, the percentage of cows with positive Chlamydophila milk PCR among the combined PCR-tested Chlamydophila-vaccinated (n = 22) and mock-vaccinated (n = 19) cows increased significantly. The difference between the percentage of Chlamydophila milk PCR-positive animals on day 0 versus day 1, 4, or 7 (P < 0.01 by Fisher exact two-tailed test) or on day 94 versus day 109 (P = 0.01) is highly significant. No significant difference in the Chlamydophila milk PCR results on any test day was observed between Chlamydophila- and mock-vaccinated cows. Both Chlamydophila and irrelevant vaccinations therefore increase Chlamydophila detection in milk for approximately 1 week, but the Chlamydophila vaccine does not eliminate or reduce Chlamydophila shedding significantly compared to an irrelevant mock vaccine.

FIG. 5.

Hyperresponders identified among Chlamydophila-vaccinated cows. Hyperresponders among Chlamydophila-vaccinated cows were identified by a twofold or greater increase of day 76 milk SCC over prevaccination SCC. Data are shown as the antilog of mean log SCC ± 95% confidence interval. The difference in the trend of milk SCC over time between the hyperresponders (n = 4) and standard responders (n = 63) is highly significant (P = 0.002 by repeated-measures ANOVA and Tukey HSD test).