Immunity, safety and protection of an Adenovirus 5 prime--Modified Vaccinia virus Ankara boost subunit vaccine against Mycobacterium avium subspecies paratuberculosis infection in calves.

Immunity, safety and protection of an Adenovirus 5 prime--Modified Vaccinia virus Ankara boost subunit vaccine against Mycobacterium avium subspecies paratuberculosis infection in calves.
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DOI:
10.1186/s13567-014-0112-9
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发表时间:
2014-10-29
影响因子:
4.4
通讯作者:
Hope JC
Hope JC
中科院分区:
农林科学2区
文献类型:
--
作者:
Bull TJ;Vrettou C;Linedale R;McGuinnes C;Strain S;McNair J;Gilbert SC;Hope JC

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疫苗接种是由鸟分枝杆菌副结核亚种(MAP)引起的约翰氏病的最具成本效益的控制措施,但目前可用的全细胞灭活制剂具有有限的功效,并且与通过结核菌素皮肤试验诊断牛结核病不相容。我们已经评估了非复制型人腺病毒5和修饰的牛痘病毒安卡拉重组体的病毒递送方案对于早期进入MAP特异性抗原(HAV)的效用,以显示对小牛模型中的挑战的保护,并广泛筛选与保护相关的差异免疫学标记。我们已经证明,HAV疫苗接种耐受性良好,可以使用区分感染和接种动物(DIVA)试验进行检测,与结核菌素无交叉反应性,并提供一定程度的抗攻毒保护,证明了在整个7个月的感染期内,接种动物缺乏粪便脱落。接种HAV疫苗的小牛对MAP衍生抗原(PPD-J)特异性CD 4+、CD 8+产生IFN-γ的T细胞群有显着的激发和加强,并且在激发后,产生早期特异性Th 17相关免疫反应,增强IFN-γ反应并保留血液中的高MAP杀伤能力。在MAP攻击后的后期阶段,HAV接种动物中的PPD-J抗原特异性IFN-γ和Th 17应答与外周菌血症的改善相对应。相比之下,缺乏IFN-γ、诱导FoxP 3 + T细胞以及增加的IL-1β和IL-10分泌指示假疫苗接种动物中的进行性感染。我们的结论是,HAV疫苗接种显示出良好的承诺,作为一种新的工具,提高牛MAP感染的控制。本文的在线版本(doi:10.1186/s13567-014-0112-9)包含补充材料,可供授权用户使用。
Vaccination is the most cost effective control measure for Johne’s disease caused by Mycobacterium avium subspecies paratuberculosis (MAP) but currently available whole cell killed formulations have limited efficacy and are incompatible with the diagnosis of bovine tuberculosis by tuberculin skin test. We have evaluated the utility of a viral delivery regimen of non-replicative human Adenovirus 5 and Modified Vaccinia virus Ankara recombinant for early entry MAP specific antigens (HAV) to show protection against challenge in a calf model and extensively screened for differential immunological markers associated with protection. We have shown that HAV vaccination was well tolerated, could be detected using a differentiation of infected and vaccinated animals (DIVA) test, showed no cross-reactivity with tuberculin and provided a degree of protection against challenge evidenced by a lack of faecal shedding in vaccinated animals that persisted throughout the 7 month infection period. Calves given HAV vaccination had significant priming and boosting of MAP derived antigen (PPD-J) specific CD4+, CD8+ IFN-γ producing T-cell populations and, upon challenge, developed early specific Th17 related immune responses, enhanced IFN-γ responses and retained a high MAP killing capacity in blood. During later phases post MAP challenge, PPD-J antigen specific IFN-γ and Th17 responses in HAV vaccinated animals corresponded with improvements in peripheral bacteraemia. By contrast a lack of IFN-γ, induction of FoxP3+ T cells and increased IL-1β and IL-10 secretion were indicative of progressive infection in Sham vaccinated animals. We conclude that HAV vaccination shows excellent promise as a new tool for improving control of MAP infection in cattle. The online version of this article (doi:10.1186/s13567-014-0112-9) contains supplementary material, which is available to authorized users.
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