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首页> 外文期刊>Vaccine >Cell recruitment and antigen trafficking in afferent lymph after injection of antigen and poly(I:C) containing liposomes, in aqueous or oil-based formulations.
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Cell recruitment and antigen trafficking in afferent lymph after injection of antigen and poly(I:C) containing liposomes, in aqueous or oil-based formulations.

机译：在水性或油基制剂中，注射抗原和含聚（I：C）的脂质体后，传入淋巴中的细胞募集和抗原运输。

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After vaccination, innate cell populations transport antigen from the tissue, via the afferent lymphatic vessels, into the local lymph node where they provide critical signals for the generation of an adaptive immune response. The present study uses a unique lymphatic cannulation model to examine, in real time, changes in afferent lymph after injection of a liposome-based delivery system, incorporating diptheria toxoid (DT) and the innate stimulator, poly(I:C). There was a dramatic but temporal recruitment of innate cell populations over time, with neutrophils and monocytes peaking at 6 h and 28 h post vaccination respectively. The number of dendritic cells (DC) did not increase over the 198 h time period, while lymphocytes were slightly elevated at the latest times, indicating the start of an adaptive response. Monocytes and neutrophils were the predominant cell types transporting antigen at the early time points while DC were the most dominant antigen-carrying cells after 78 h, predominantly the Sirp- alpha high DC subtype. Resuspending liposomes in oil instead of aqueous solutions has recently been shown to dramatically increase the level and persistence of an immune response and forms the basis of the novel adjuvant formulations, Vaccimax copyright and Depovax copyright . In the present study, formulation of the DT and poly(I:C) containing liposomes in an oil carrier dramatically reduced antigen transport to the draining lymph nodes. Examination of the injection site revealed the creation of an ectopic lymphoid tissue with prominent antigen foci and organized lymphoid cells, providing a possible mechanism for the persistence of an immune response in liposome-in-oil adjuvant formulation. Together, the present studies demonstrate the real-time innate in vivo response to vaccination of two novel liposome-based adjuvant systems and the dramatic effect of different carrier formulations
机译：接种疫苗后，先天细胞群体通过传入的淋巴管将抗原从组织转运到局部淋巴结，在那里它们为产生适应性免疫应答提供关键信号。本研究使用独特的淋巴管插管模型，实时检查注射基于脂质体的递送系统，并结合白喉类毒素（DT）和先天性刺激物聚（I：C）后传入淋巴的变化。随着时间的流逝，先天细胞群出现了戏剧性但短暂的募集，中性粒细胞和单核细胞分别在接种后6 h和28 h达到峰值。在198 h的时间内树突状细胞（DC）的数量没有增加，而淋巴细胞在最近的时间略有升高，表明适应性反应已经开始。单核细胞和中性粒细胞是在早期时间点转运抗原的主要细胞类型，而DC是78 h后最主要的抗原携带细胞，主要是Sirp-alpha high DC亚型。在油中而不是在水溶液中重悬脂质体近来已被证明可以显着提高免疫应答的水平和持久性，并形成新型佐剂制剂，Vaccimax版权和Depovax版权的基础。在本研究中，在油载体中含有DT和聚（I：C）脂质体的制剂显着降低了抗原向引流淋巴结的转运。注射部位的检查揭示了异位淋巴组织的形成，该异位淋巴组织具有突出的抗原灶和有组织的淋巴样细胞，为油中脂质体佐剂制剂中的免疫应答的持续提供了可能的机制。总之，本研究证明了两种基于脂质体的新型佐剂系统对疫苗接种的实时先天体内反应以及不同载体制剂的显着效果

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