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评估疫苗候选株布鲁氏菌 16MΔvjbR 株在山羊中的安全性。

Evaluation of the safety profile of the vaccine candidate Brucella melitensis 16MΔvjbR strain in goats.

机构信息

Instituto de Patobiología, CICVyA-INTA (Instituto Nacional de Tecnología Agropecuaria), Nicolas Repetto y de Los Reseros s/n (B1686), Hurlingham, Bs. As., Argentina.

Department of Veterinary Pathobiology, College of Veterinary Medicine & Biomedical Sciences, Texas A&M University, 4467 TAMU, College Station, TX 77843, USA.

出版信息

Vaccine. 2021 Jan 15;39(3):617-625. doi: 10.1016/j.vaccine.2020.11.033. Epub 2020 Dec 13.

DOI:10.1016/j.vaccine.2020.11.033
PMID:33328142
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8730362/
Abstract

Small ruminant brucellosis is caused by the Gram negative cocci-bacillus Brucella (B.) melitensis, the most virulent Brucella species for humans. In goats and sheep, middle to late-term gestation abortion, stillbirths and the delivery of weak infected offspring are the characteristic clinical signs of the disease. Vaccination with the currently available Rev. 1 vaccine is the best option to prevent and control the disease, although it is far from ideal. In this study, we investigate the safety of the B. melitensis 16MΔvjbR strain during a 15-month period beginning at vaccination of young goats, impregnation, delivery and lactation. Forty, 4 to 6 months old, healthy female crossbreed goats were randomly divided into four groups (n = 10) and immunized subcutaneously with a single vaccine dose containing 1x10 CFU of B. melitensis 16MΔvjbR delivered in alginate microcapsules or non-encapsulated. Controls received empty capsules or the commercially available Rev.1 vaccine. Seven months post-vaccination, when animals were sexually mature, all goats were naturally bred using brucellosis-free males, and allowed to carry pregnancies to term. Blood samples to assess the humoral immune response were collected throughout the study. At two months post-delivery, all dams and their offspring were euthanized and a necropsy was performed to collect samples for bacteriology and histology. Interestingly, none of the animals that received the vaccine candidate regardless of the formulation exhibited any clinical signs associated with vaccination nor shed the vaccine strain through saliva, vagina or the milk. Gross and histopathologic changes in all nannies and offspring were unremarkable with no evidence of tissue colonization or vertical transmission to fetuses. Altogether, these data demonstrate that vaccination with the mutant strain 16MΔvjbR is safe for use in the non-pregnant primary host.

摘要

小反刍动物布鲁氏菌病是由革兰氏阴性球杆菌布鲁氏菌(B.)melitensis 引起的,该菌是对人类最具毒性的布鲁氏菌种。在山羊和绵羊中,妊娠中期至晚期流产、死产和产下虚弱感染的后代是该疾病的特征性临床症状。使用目前可用的 Rev.1 疫苗进行免疫接种是预防和控制该疾病的最佳选择,尽管它远非理想。在这项研究中,我们研究了在对年轻山羊进行疫苗接种、受孕、分娩和哺乳开始后的 15 个月期间,B. melitensis 16MΔvjbR 菌株的安全性。40 只 4 至 6 个月大的健康雌性杂交山羊被随机分为四组(n = 10),并通过皮下接种含有 1x10 CFU 的 B. melitensis 16MΔvjbR 的单一疫苗剂量进行免疫,该疫苗以藻酸盐微胶囊或非包裹形式递送。对照组接受空胶囊或市售的 Rev.1 疫苗。疫苗接种后 7 个月,当动物性成熟时,所有山羊均使用无布鲁氏菌的雄性进行自然繁殖,并允许其妊娠至足月。在整个研究过程中采集血液样本以评估体液免疫反应。分娩后两个月,所有母羊及其后代均被安乐死,并进行尸检以采集样本进行细菌学和组织学检查。有趣的是,无论使用哪种制剂,接受候选疫苗的动物均未表现出与疫苗接种相关的任何临床症状,也未通过唾液、阴道或乳汁排出疫苗菌株。所有保姆和后代的大体和组织病理学变化均无明显异常,无组织定植或垂直传播给胎儿的证据。总而言之,这些数据表明,使用突变株 16MΔvjbR 进行免疫接种对非妊娠的原发性宿主是安全的。

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