Oral Vaccination of Free-Living Badgers (Meles meles) with Bacille Calmette Guerin (BCG) Vaccine Confers Protection against Tuberculosis

Oral Vaccination of Free-Living Badgers (Meles meles) with Bacille Calmette Guerin (BCG) Vaccine Confers Protection against Tuberculosis
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DOI:
10.1371/journal.pone.0168851
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发表时间:
2017-01-25
期刊:
影响因子:
3.7
通讯作者:
Corner, Leigh A. L.
Corner, Leigh A. L.
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Gormley, Eamonn;Bhuachalla, Deirdre Ni;Corner, Leigh A. L.

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进行了一项现场试验,以调查自由生活的獾口服疫苗接种对自然传播的牛分枝杆菌感染的影响。在三年的时间里,獾在三个区域进行了七次扫描,并被分配进行口服脂质封装卡介苗疫苗 (Liporale-BCG) 或安慰剂疫苗接种。登记在 A 区的獾注射了安慰剂,而登记在 C 区的所有獾都接种了卡介苗。参加中间区域 B 区的獾被随机分配为 50:50,接受疫苗或安慰剂治疗。每个区域的治疗均保持盲法,直至研究期结束。感兴趣的结果是使用 BrockTB Stat-Pak 侧流血清学测试测量血清转化事件时间的结核病病例,并辅以尸检。在发生血清转化的接种疫苗獾中,与未接种疫苗的动物(230 天)相比,血清转化的中位时间(413 天)明显更长(p = 0.04)。生存分析(血清转化时间建模)显示,在整个试验期间,A 区和 C 区接种疫苗的獾和未接种疫苗的獾之间的血清转化率存在显着差异 (p = 0.015)。对于在扫描 1-2 期间登记的獾,根据危险率比确定的疫苗效力 (VE) 为 36%(95% CI:-62%-75%)。对于在第 3-6 次扫描期间登记在这些区域的獾,VE 为 84%(95% CI:29%-97%)。这表明 VE 随着疫苗覆盖率的增加而增加。试验结束时对獾的尸检还显示,与未接种疫苗的 A 区 (26%) 相比,接种疫苗的 C 区 (9%) 中出现牛支原体培养证实病变的动物比例存在显着差异。这些结果表明,口服卡介苗疫苗可以为獾提供保护,并可用于降低獾感染结核病的发病率。
A field trial was conducted to investigate the impact of oral vaccination of free-living badgers against natural-transmitted Mycobacterium bovis infection. For a period of three years badgers were captured over seven sweeps in three zones and assigned for oral vaccination with a lipid-encapsulated BCG vaccine (Liporale-BCG) or with placebo. Badgers enrolled in Zone A were administered placebo while all badgers enrolled in Zone C were vaccinated with BCG. Badgers enrolled in the middle area, Zone B, were randomly assigned 50: 50 for treatment with vaccine or placebo. Treatment in each zone remained blinded until the end of the study period. The outcome of interest was incident cases of tuberculosis measured as time to seroconversion events using the BrockTB Stat-Pak lateral flow serology test, supplemented with post-mortem examination. Among the vaccinated badgers that seroconverted, the median time to seroconversion (413 days) was significantly longer (p = 0.04) when compared with non-vaccinated animals (230 days). Survival analysis (modelling time to seroconversion) revealed that there was a significant difference in the rate of seroconversion between vaccinated and non-vaccinated badgers in Zones A and C throughout the trial period (p = 0.015). For badgers enrolled during sweeps 1-2 the Vaccine Efficacy (VE) determined from hazard rate ratios was 36% (95% CI: -62%-75%). For badgers enrolled in these zones during sweeps 3-6, the VE was 84% (95% CI: 29%-97%). This indicated that VE increased with the level of vaccine coverage. Post-mortem examination of badgers at the end of the trial also revealed a significant difference in the proportion of animals presenting with M. bovis culture confirmed lesions in vaccinated Zone C (9%) compared with non-vaccinated Zone A (26%). These results demonstrate that oral BCG vaccination confers protection to badgers and could be used to reduce incident rates in tuberculosis-infected populations of badgers.