Open AccessVaccine Candidate Brucella melitensis 16M ΔvjbR Is Safe in a Pregnant Sheep Model and Confers Protection
Author(s) -
Martha E. Hensel,
Daniel G. García-González,
Sankar P. Chaki,
Airn E. Hartwig,
Paul Gordy,
Richard A. Bowen,
Thomas A. Ficht,
Angela M. ArenasGamboa
Publication year - 2020
Publication title -
msphere
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.749
H-Index - 39
ISSN - 2379-5042
DOI - 10.1128/msphere.00120-20
Subject(s) - brucella melitensis , brucellosis , vaccination , virulence , virology , pregnancy , disease , biology , brucella , attenuated vaccine , zoonotic disease , medicine , immunology , biochemistry , genetics , pathology , gene
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 16M ΔvjbR , pregnant sheep ( n = 6) were vaccinated subcutaneously with 1 × 10 10 CFU/ml of 16M ΔvjbR or 1 × 10 9 CFU/ml Rev. 1 at a highly susceptible stage of gestation (approximately 70 days). 16M ΔvjbR 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 16M ΔvjbR 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 × 10 7 CFU/ml B. melitensis Protection was similar between Rev. 1 and 16M ΔvjbR , with no statistical difference in colonization in the target organs. Overall, the 16M ΔvjbR 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. IMPORTANCE Brucellosis is one of the most commonly reported zoonotic disease with a worldwide distribution. Of the 12 Brucella species, Brucella melitensis is considered the most virulent and causes reproductive failure (abortions/stillbirths) in small ruminants, which can spread the disease to other animals or to humans. Vaccination of small ruminants is a key measure used to protect both human and animal health. However, the commercially available live-attenuated vaccine for Brucella melitensis Rev. 1 retains virulence and can cause disease in animals and humans. In order to evaluate the safety and efficacy in sheep, we vaccinated pregnant sheep with 16M ΔvjbR Our results indicate that 16M ΔvjbR was safer for use during pregnancy, provided a similar level of protection as Rev. 1, and could be considered an improved candidate for future vaccine trials.