中文摘要：MF59是一种人类流感疫苗的水包油乳状佐剂。已有研究表明，MF59能够在注射部位形成免疫活性环境从而促进抗原呈递细胞（APCs）等免疫细胞的富集；这些细胞可以促进抗原被吞噬，并将抗原运载到引流淋巴结(dLN)，促使抗原在此富集。本研究测定了APC的基因型及其引流淋巴结中运载的抗体类型、引流淋巴结(dLN)细胞区隔内抗原分布和藻红蛋白（PE）引起的体液反应，并应用卵清蛋白抗原模型测定了引流淋巴结APCs诱导抗原特异性CD4 T细胞增殖的能力。结果表明，MF59能够促进引流淋巴结单核细胞富集区单核细胞向树突状细胞的增殖，这种增殖可以在淋巴结髓室内产生；研究还表明，单核细胞向树突状细胞是采用MF59佐剂免疫后引流淋巴结中抗原负载和激活呈递细胞（APCs）的主要来源。该研究结果表明，MF59能够直接促进引流淋巴结内形成免疫活性环境，为深入了解乳状疫苗佐剂的功能机理提供了重要参考。
 
外文摘要：MF59 is an oil-in-water emulsion adjuvant approved for human influenza vaccination in European Union. The mode of action of MF59 is not fully elucidated yet, but results from several years of investigation indicate that MF59 establishes an immunocompetent environment at injection site which promotes recruitment of immune cells, including antigen presenting cells (APCs), that are facilitated to engulf antigen and transport it to draining lymph node (dLN) where the antigen is accumulated. In vitro studies showed that MF59 promotes the differentiation of monocytes to dendritic cells (Mo-DCs). Since after immunization with MF59, monocytes are rapidly recruited both at the injection site and in dLN and appear to have a morphological change toward a DC-like phenotype, we asked whether MF59 could play a role in inducing differentiation of Mo-DC in vivo. To address this question we immunized mice with the auto-fluorescent protein Phycoerythrin (PE) as model antigen, in presence or absence of MF59. We measured the APC phenotype and their antigen uptake within dLNs, the antigen distribution within the dLN compartments and the humoral response to PE. In addition, using Ovalbumin as model antigen, we measured the capacity of dLN APCs to induce antigen-specific CD4 T cell proliferation. Here, we show, for the first time, that MF59 promotes differentiation of Mo-DCs within dLNs from intranodal recruited monocytes and we suggest that this differentiation could take place in the medullary compartment of the LN. In addition we show that the Mo-DC subset represents the major source of antigen-loaded and activated APCs within the dLN when immunizing with MF59. Interestingly, this finding correlates with the enhanced triggering of antigen-specific CD4 T cell response induced by LN APCs. This study therefore demonstrates that MF59 is able to promote an immunocompetent environment also directly within the dLN, offering a novel insight on the mechanism of action of vaccine adjuvants based on emulsions.
外文关键词：INTRAMUSCULAR INJECTION; IMMUNITY; IMMUNIZATION; TRAFFICKING; SUBSETS; BIOLOGY; INDUCE
作者：Cioncada, R; Maddaluno, M; Vo, HTM; Woodruff, M; Woodruff, M; Sammicheli, C; Tortoli, M; Pezzicoli, A; De Gregorio, E; Carroll, MC; D'Oro, U; Piccioli, D
作者单位：意大利葛兰素史克
期刊名称：PLOS ONE
期刊影响因子：2.806
出版年份：2017
出版刊次：10
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