Vaccine Candidate <named-content content-type="genus-species">Brucella melitensis</named-content> 16M<italic toggle="yes">ΔvjbR</italic> 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. T...

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Autores principales:	Martha E. Hensel, Daniel G. Garcia-Gonzalez, Sankar P. Chaki, Airn Hartwig, Paul W. Gordy, Richard Bowen, Thomas A. Ficht, Angela M. Arenas-Gamboa
Formato:	article
Lenguaje:	EN
Publicado:	American Society for Microbiology 2020
Materias:	Brucella melitensis brucellosis ovine pregnancy veterinary vaccine development Microbiology QR1-502
Acceso en línea:	https://doaj.org/article/4aac9acedd874c8dba8aa494555dd810
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spelling	oai:doaj.org-article:4aac9acedd874c8dba8aa494555dd8102021-11-15T15:30:15ZVaccine Candidate <named-content content-type="genus-species">Brucella melitensis</named-content> 16M<italic toggle="yes">ΔvjbR</italic> Is Safe in a Pregnant Sheep Model and Confers Protection10.1128/mSphere.00120-202379-5042https://doaj.org/article/4aac9acedd874c8dba8aa494555dd8102020-06-01T00:00:00Zhttps://journals.asm.org/doi/10.1128/mSphere.00120-20https://doaj.org/toc/2379-5042ABSTRACT 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. 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 16MΔvjbR. Our results indicate that 16MΔvjbR 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.Martha E. HenselDaniel G. Garcia-GonzalezSankar P. ChakiAirn HartwigPaul W. GordyRichard BowenThomas A. FichtAngela M. Arenas-GamboaAmerican Society for MicrobiologyarticleBrucella melitensisbrucellosisovinepregnancyveterinary vaccine developmentMicrobiologyQR1-502ENmSphere, Vol 5, Iss 3 (2020)
institution	DOAJ
collection	DOAJ
language	EN
topic	Brucella melitensis brucellosis ovine pregnancy veterinary vaccine development Microbiology QR1-502
spellingShingle	Brucella melitensis brucellosis ovine pregnancy veterinary vaccine development Microbiology QR1-502 Martha E. Hensel Daniel G. Garcia-Gonzalez Sankar P. Chaki Airn Hartwig Paul W. Gordy Richard Bowen Thomas A. Ficht Angela M. Arenas-Gamboa Vaccine Candidate <named-content content-type="genus-species">Brucella melitensis</named-content> 16M<italic toggle="yes">ΔvjbR</italic> Is Safe in a Pregnant Sheep Model and Confers Protection
description	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. 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 16MΔvjbR. Our results indicate that 16MΔvjbR 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.
format	article
author	Martha E. Hensel Daniel G. Garcia-Gonzalez Sankar P. Chaki Airn Hartwig Paul W. Gordy Richard Bowen Thomas A. Ficht Angela M. Arenas-Gamboa
author_facet	Martha E. Hensel Daniel G. Garcia-Gonzalez Sankar P. Chaki Airn Hartwig Paul W. Gordy Richard Bowen Thomas A. Ficht Angela M. Arenas-Gamboa
author_sort	Martha E. Hensel
title	Vaccine Candidate <named-content content-type="genus-species">Brucella melitensis</named-content> 16M<italic toggle="yes">ΔvjbR</italic> Is Safe in a Pregnant Sheep Model and Confers Protection
title_short	Vaccine Candidate <named-content content-type="genus-species">Brucella melitensis</named-content> 16M<italic toggle="yes">ΔvjbR</italic> Is Safe in a Pregnant Sheep Model and Confers Protection
title_full	Vaccine Candidate <named-content content-type="genus-species">Brucella melitensis</named-content> 16M<italic toggle="yes">ΔvjbR</italic> Is Safe in a Pregnant Sheep Model and Confers Protection
title_fullStr	Vaccine Candidate <named-content content-type="genus-species">Brucella melitensis</named-content> 16M<italic toggle="yes">ΔvjbR</italic> Is Safe in a Pregnant Sheep Model and Confers Protection
title_full_unstemmed	Vaccine Candidate <named-content content-type="genus-species">Brucella melitensis</named-content> 16M<italic toggle="yes">ΔvjbR</italic> Is Safe in a Pregnant Sheep Model and Confers Protection
title_sort	vaccine candidate <named-content content-type="genus-species">brucella melitensis</named-content> 16m<italic toggle="yes">δvjbr</italic> is safe in a pregnant sheep model and confers protection
publisher	American Society for Microbiology
publishDate	2020
url	https://doaj.org/article/4aac9acedd874c8dba8aa494555dd810
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Vaccine Candidate <named-content content-type="genus-species">Brucella melitensis</named-content> 16M<italic toggle="yes">ΔvjbR</italic> Is Safe in a Pregnant Sheep Model and Confers Protection

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