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用活卡介苗和灭活牛分枝杆菌候选疫苗接种后犊牛的免疫反应概况。

Immune response profiles of calves following vaccination with live BCG and inactivated Mycobacterium bovis vaccine candidates.

作者信息

van der Heijden E M D L, Chileshe J, Vernooij J C M, Gortazar C, Juste R A, Sevilla I, Crafford J E, Rutten V P M G, Michel A L

机构信息

Department of Infectious Diseases & Immunology, Division of Immunology, Faculty of Veterinary Medicine, Utrecht University, Utrecht, The Netherlands.

Bovine Tuberculosis and Brucellosis Research Programme, Department of Veterinary Tropical Diseases, Faculty of Veterinary Science, University of Pretoria, Pretoria, South Africa.

出版信息

PLoS One. 2017 Nov 20;12(11):e0188448. doi: 10.1371/journal.pone.0188448. eCollection 2017.

Abstract

Conventional control and eradication strategies for bovine tuberculosis (BTB) face tremendous difficulties in developing countries; countries with wildlife reservoirs, a complex wildlife-livestock-human interface or a lack of veterinary and veterinary public health surveillance. Vaccination of cattle and other species might in some cases provide the only suitable control strategy for BTB, while in others it may supplement existing test-and-slaughter schemes. However, the use of live BCG has several limitations and the global rise of HIV/AIDS infections has furthermore warranted the exploration of inactivated vaccine preparations. The aim of this study was to compare the immune response profiles in response to parenteral vaccination with live BCG and two inactivated vaccine candidates in cattle. Twenty-four mixed breed calves (Bos taurus) aged 4-6 months, were allocated to one of four groups and vaccinated sub-cutaneously with live M. bovis BCG (Danish 1331), formalin-inactivated M. bovis BCG, heat-killed M. bovis or PBS/Montanide™ (control). Interferon-γ responsiveness and antibody production were measured prior to vaccination and at weekly intervals thereafter for twelve weeks. At nine weeks post-priming, animals were skin tested using tuberculins and MTBC specific protein cocktails and subsequently challenged through intranodular injection of live M. bovis BCG. The animals in the heat-killed M. bovis group demonstrated strong and sustained cell-mediated and humoral immune responses, significantly higher than the control group in response to vaccination, which may indicate a protective immune profile. Animals in this group showed reactivity to the skin test reagents, confirming good vaccine take. Lastly, although not statistically significant, recovery of BCG after challenge was lowest in the heat-killed M. bovis group. In conclusion, the parenteral heat-killed M. bovis vaccine proved to be clearly immunogenic in cattle in the present study, urging further evaluation of the vaccine in challenge studies using virulent M. bovis and assessment of vaccine efficacy in field conditions.

摘要

在发展中国家,牛结核病(BTB)的传统控制和根除策略面临巨大困难;这些国家存在野生动物宿主、野生动物-家畜-人类界面复杂或缺乏兽医及兽医公共卫生监测。在某些情况下,给牛和其他物种接种疫苗可能是控制牛结核病的唯一合适策略,而在其他情况下,它可能补充现有的检测和屠宰计划。然而,使用活卡介苗有几个局限性,而且全球艾滋病毒/艾滋病感染率的上升进一步促使人们探索灭活疫苗制剂。本研究的目的是比较牛经皮下接种活卡介苗和两种候选灭活疫苗后的免疫反应情况。将24头4至6个月大的混种犊牛(Bos taurus)分为四组之一,分别皮下接种活牛分枝杆菌卡介苗(丹麦1331株)、福尔马林灭活的牛分枝杆菌卡介苗、热灭活的牛分枝杆菌或PBS/蒙他尼™(对照)。在接种前及之后的12周内每周测量一次干扰素-γ反应性和抗体产生情况。在初次免疫后9周,用结核菌素和结核分枝杆菌复合群特异性蛋白混合物对动物进行皮肤试验,随后通过结节内注射活牛分枝杆菌卡介苗进行攻毒。热灭活牛分枝杆菌组的动物表现出强烈且持续的细胞介导免疫和体液免疫反应,接种疫苗后的反应明显高于对照组,这可能表明具有保护性免疫特征。该组动物对皮肤试验试剂有反应,证实疫苗接种效果良好。最后,虽然无统计学意义,但热灭活牛分枝杆菌组攻毒后卡介苗的恢复率最低。总之,在本研究中,经皮下接种热灭活牛分枝杆菌疫苗在牛中显示出明显的免疫原性,促使在使用强毒牛分枝杆菌的攻毒研究中进一步评估该疫苗,并在现场条件下评估疫苗效力。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8ea2/5695775/7fed552011c5/pone.0188448.g001.jpg

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