Department of Infectious Diseases and Immunology, Faculty of Veterinary Medicine, Utrecht University, Yalelaan 1, 3584CL Utrecht, The Netherlands.
Vaccine. 2013 Oct 1;31(42):4720-7. doi: 10.1016/j.vaccine.2013.08.021. Epub 2013 Aug 20.
Bovine paratuberculosis is a highly prevalent chronic infection of the small intestine in cattle, caused by Mycobacterium avium subspecies paratuberculosis (MAP). In earlier studies we showed the protective effect of Hsp70/DDA subunit vaccination against paratuberculosis. In the current study we set out to measure primary immune responses generated at the site of Hsp70 vaccination. Lymph vessel cannulation was performed to obtain efferent lymph from the prescapular lymph node draining the neck area where the vaccine was applied. Hsp70 vaccination induced a significant increase of CD21(+) B cells in efferent lymph, accounting for up to 40% of efferent cells post-vaccination. Proliferation (Ki67(+)) within the CD21(+) B cell and CD4(+) T cell populations peaked between day 3 and day 5 post-vaccination. From day 7, Hsp70-specific antibody secreting cells (ASCs) could be detected in efferent lymph. Hsp70-specific antibodies, mainly of the IgG1 isotype, were also detected from this time point onwards. However, post-vaccination IFN-γ production in efferent lymph was non-sustained. In conclusion, Hsp70-vaccination induces only limited Th1 type immune responsiveness as reflected in efferent lymph draining the vaccination site. This is in line with our previous observations in peripheral blood. The main primary immunological outcome of the Hsp70/DDA subunit vaccination is B cell activation and abundant Hsp70-specific IgG1 production. This warrants the question whether Hsp70-specific antibodies contribute to the observed protective effect of Hsp70 vaccination in calves.
牛副结核病是一种高度流行的牛小肠慢性感染，由鸟分枝杆菌副结核亚种（MAP）引起。在早期的研究中，我们表明 Hsp70/DDA 亚单位疫苗接种对副结核病具有保护作用。在当前的研究中，我们旨在测量 Hsp70 疫苗接种部位产生的初级免疫反应。进行淋巴管插管以从颈区引流疫苗接种部位的颈前淋巴结获得输出淋巴。Hsp70 疫苗接种诱导输出淋巴中 CD21(+)B 细胞显著增加，接种后可达 40%的输出细胞。CD21(+)B 细胞和 CD4(+)T 细胞群中的增殖（Ki67(+))在接种后第 3 天至第 5 天达到峰值。从第 7 天开始，可以在输出淋巴中检测到 Hsp70 特异性抗体分泌细胞（ASC）。从此时起，还可以检测到 Hsp70 特异性抗体，主要是 IgG1 同种型。然而，接种后 IFN-γ在输出淋巴中的产生是非持续的。总之，Hsp70 疫苗接种仅诱导有限的 Th1 型免疫反应，这反映在疫苗接种部位引流的输出淋巴中。这与我们以前在外周血中的观察结果一致。Hsp70/DDA 亚单位疫苗接种的主要初级免疫学结果是 B 细胞激活和大量 Hsp70 特异性 IgG1 产生。这就提出了一个问题，即 Hsp70 特异性抗体是否有助于观察到 Hsp70 疫苗接种在小牛中的保护作用。
