Vaccine candidate Brucella melitensis 16MΔvjbR is safe in a pregnant sheep model and confers protection

Abstract

As a natural host species for Brucella melitensis, pregnant sheep offer an ideal model to evaluate vaccine candidates for safety. B. melitensis strain Rev. 1 has been used almost exclusively to prevent brucellosis in small ruminants, but it causes abortions when given to pregnant animals. To evaluate the comparative safety of the candidate Brucella melitensis 16MΔvjbR, pregnant sheep (n = 6) were vaccinated subcutaneously with 1 × 10¹⁰ CFU/ml of 16MΔvjbR or 1 × 10⁹ CFU/ml Rev. 1 at a highly susceptible stage of gestation (approximately 70 days). 16MΔvjbR resulted in only 1 abortion (1 of 6) compared with 4 of 6 (66.7%) abortions in the Rev. 1 cohort. The placenta was evaluated by culture to determine if vaccination resulted in colonization. As another measure of safety, effects of B. melitensis on the fetus/offspring (vertical transmission) was evaluated by culture and histopathology of fetal tissues to determine if vaccination prevented infection of the fetus. Vaccination with 16MΔvjbR resulted in less vertical transmission than Rev. 1. To determine if vaccination was efficacious and could reduce tissue colonization in sheep, the same cohort of sheep were challenged 5 weeks postpartum by conjunctival inoculation with 1 × 10⁷ CFU/ml B. melitensis. Protection was similar between Rev. 1 and 16MΔvjbR, with no statistical difference in colonization in the target organs. Overall, the 16MΔvjbR vaccine was considered safer than Rev. 1 based on a reduced number of abortions and limited infection in the offspring. Future experiments are needed to further refine the vaccine dose to increase the safety margin and to evaluate protection in pregnant ewes.