Evaluation of the Efficacy of the <named-content content-type="genus-species">Brucella canis</named-content> RM6/66 Δ<italic toggle="yes">vjbR</italic> Vaccine Candidate for Protection against <named-content content-type="genus-species">B. canis</named-content> Infection in Mice

ABSTRACT Brucella canis is a Gram-negative, facultative intracellular bacterium and the causative agent of canine brucellosis, a highly contagious disease of dogs that can be transmitted to humans. Unfortunately, no vaccine is available to prevent infection. We recently characterized the kinetics of...

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Autores principales:	Lauren W. Stranahan, Sankar P. Chaki, Daniel G. Garcia-Gonzalez, Omar H. Khalaf, Angela M. Arenas-Gamboa
Formato:	article
Lenguaje:	EN
Publicado:	American Society for Microbiology 2020
Materias:	Brucella canis brucellosis modified live vaccine mouse model vaccine vaccine efficacy Microbiology QR1-502
Acceso en línea:	https://doaj.org/article/bfd0a6062cae4fb5b97c1b994f1dc968
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spelling	oai:doaj.org-article:bfd0a6062cae4fb5b97c1b994f1dc9682021-11-15T15:30:15ZEvaluation of the Efficacy of the <named-content content-type="genus-species">Brucella canis</named-content> RM6/66 Δ<italic toggle="yes">vjbR</italic> Vaccine Candidate for Protection against <named-content content-type="genus-species">B. canis</named-content> Infection in Mice10.1128/mSphere.00172-202379-5042https://doaj.org/article/bfd0a6062cae4fb5b97c1b994f1dc9682020-06-01T00:00:00Zhttps://journals.asm.org/doi/10.1128/mSphere.00172-20https://doaj.org/toc/2379-5042ABSTRACT Brucella canis is a Gram-negative, facultative intracellular bacterium and the causative agent of canine brucellosis, a highly contagious disease of dogs that can be transmitted to humans. Unfortunately, no vaccine is available to prevent infection. We recently characterized the kinetics of B. canis infection in the mouse model, establishing the required dose necessary to achieve systemic infection. The objective of this study was to investigate the utility of the mouse model in assessing canine brucellosis vaccine candidates and to subsequently investigate the safety and efficacy of a live attenuated vaccine, the B. canis RM6/66 ΔvjbR strain. Mice vaccinated with a dose of 109 CFU of the vaccine strain by both intraperitoneal and subcutaneous routes were afforded significant protection against organ colonization and development of histopathologic lesions following intraperitoneal challenge. Addition of an adjuvant or a booster dose 2 weeks following initial vaccination did not alter protection levels. Vaccination also resulted in a robust humoral immune response in mice, and B. canis RM6/66 ΔvjbR was capable of activating canine dendritic cells in vitro. These data demonstrate that the B. canis RM6/66 ΔvjbR strain shows promise as a vaccine for canine brucellosis and validates the mouse model for future vaccine efficacy studies. IMPORTANCE Canine brucellosis, caused by Brucella canis, is the primary cause of reproductive failure in dogs and represents a public health concern due to its zoonotic nature. Cases in dogs in the United States have been increasing due to the persistent nature of the bacterium, deficiencies in current diagnostic testing, and, most importantly, the lack of a protective vaccine. Current estimates place the seroprevalence of B. canis in the southern United States at 7% to 8%, but with the unprecedented rates of animals moving across state and international borders and the lack of federal regulations in regard to testing, the true seroprevalence of B. canis in the United States may very well be higher. Vaccination represents the most effective method of brucellosis control and, in response to the demand for a vaccine against B. canis, we have developed the live attenuated B. canis RM6/66 ΔvjbR vaccine strain capable of protecting mice against challenge.Lauren W. StranahanSankar P. ChakiDaniel G. Garcia-GonzalezOmar H. KhalafAngela M. Arenas-GamboaAmerican Society for MicrobiologyarticleBrucella canisbrucellosismodified live vaccinemouse modelvaccinevaccine efficacyMicrobiologyQR1-502ENmSphere, Vol 5, Iss 3 (2020)
institution	DOAJ
collection	DOAJ
language	EN
topic	Brucella canis brucellosis modified live vaccine mouse model vaccine vaccine efficacy Microbiology QR1-502
spellingShingle	Brucella canis brucellosis modified live vaccine mouse model vaccine vaccine efficacy Microbiology QR1-502 Lauren W. Stranahan Sankar P. Chaki Daniel G. Garcia-Gonzalez Omar H. Khalaf Angela M. Arenas-Gamboa Evaluation of the Efficacy of the <named-content content-type="genus-species">Brucella canis</named-content> RM6/66 Δ<italic toggle="yes">vjbR</italic> Vaccine Candidate for Protection against <named-content content-type="genus-species">B. canis</named-content> Infection in Mice
description	ABSTRACT Brucella canis is a Gram-negative, facultative intracellular bacterium and the causative agent of canine brucellosis, a highly contagious disease of dogs that can be transmitted to humans. Unfortunately, no vaccine is available to prevent infection. We recently characterized the kinetics of B. canis infection in the mouse model, establishing the required dose necessary to achieve systemic infection. The objective of this study was to investigate the utility of the mouse model in assessing canine brucellosis vaccine candidates and to subsequently investigate the safety and efficacy of a live attenuated vaccine, the B. canis RM6/66 ΔvjbR strain. Mice vaccinated with a dose of 109 CFU of the vaccine strain by both intraperitoneal and subcutaneous routes were afforded significant protection against organ colonization and development of histopathologic lesions following intraperitoneal challenge. Addition of an adjuvant or a booster dose 2 weeks following initial vaccination did not alter protection levels. Vaccination also resulted in a robust humoral immune response in mice, and B. canis RM6/66 ΔvjbR was capable of activating canine dendritic cells in vitro. These data demonstrate that the B. canis RM6/66 ΔvjbR strain shows promise as a vaccine for canine brucellosis and validates the mouse model for future vaccine efficacy studies. IMPORTANCE Canine brucellosis, caused by Brucella canis, is the primary cause of reproductive failure in dogs and represents a public health concern due to its zoonotic nature. Cases in dogs in the United States have been increasing due to the persistent nature of the bacterium, deficiencies in current diagnostic testing, and, most importantly, the lack of a protective vaccine. Current estimates place the seroprevalence of B. canis in the southern United States at 7% to 8%, but with the unprecedented rates of animals moving across state and international borders and the lack of federal regulations in regard to testing, the true seroprevalence of B. canis in the United States may very well be higher. Vaccination represents the most effective method of brucellosis control and, in response to the demand for a vaccine against B. canis, we have developed the live attenuated B. canis RM6/66 ΔvjbR vaccine strain capable of protecting mice against challenge.
format	article
author	Lauren W. Stranahan Sankar P. Chaki Daniel G. Garcia-Gonzalez Omar H. Khalaf Angela M. Arenas-Gamboa
author_facet	Lauren W. Stranahan Sankar P. Chaki Daniel G. Garcia-Gonzalez Omar H. Khalaf Angela M. Arenas-Gamboa
author_sort	Lauren W. Stranahan
title	Evaluation of the Efficacy of the <named-content content-type="genus-species">Brucella canis</named-content> RM6/66 Δ<italic toggle="yes">vjbR</italic> Vaccine Candidate for Protection against <named-content content-type="genus-species">B. canis</named-content> Infection in Mice
title_short	Evaluation of the Efficacy of the <named-content content-type="genus-species">Brucella canis</named-content> RM6/66 Δ<italic toggle="yes">vjbR</italic> Vaccine Candidate for Protection against <named-content content-type="genus-species">B. canis</named-content> Infection in Mice
title_full	Evaluation of the Efficacy of the <named-content content-type="genus-species">Brucella canis</named-content> RM6/66 Δ<italic toggle="yes">vjbR</italic> Vaccine Candidate for Protection against <named-content content-type="genus-species">B. canis</named-content> Infection in Mice
title_fullStr	Evaluation of the Efficacy of the <named-content content-type="genus-species">Brucella canis</named-content> RM6/66 Δ<italic toggle="yes">vjbR</italic> Vaccine Candidate for Protection against <named-content content-type="genus-species">B. canis</named-content> Infection in Mice
title_full_unstemmed	Evaluation of the Efficacy of the <named-content content-type="genus-species">Brucella canis</named-content> RM6/66 Δ<italic toggle="yes">vjbR</italic> Vaccine Candidate for Protection against <named-content content-type="genus-species">B. canis</named-content> Infection in Mice
title_sort	evaluation of the efficacy of the <named-content content-type="genus-species">brucella canis</named-content> rm6/66 δ<italic toggle="yes">vjbr</italic> vaccine candidate for protection against <named-content content-type="genus-species">b. canis</named-content> infection in mice
publisher	American Society for Microbiology
publishDate	2020
url	https://doaj.org/article/bfd0a6062cae4fb5b97c1b994f1dc968
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Evaluation of the Efficacy of the <named-content content-type="genus-species">Brucella canis</named-content> RM6/66 Δ<italic toggle="yes">vjbR</italic> Vaccine Candidate for Protection against <named-content content-type="genus-species">B. canis</named-content> Infection in Mice

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