The clinically successful adjuvant MF59 is used in seasonal influenza vaccines, which is proposed to enhance immunity by creating an immune‐competent microenvironment in the muscle that allows recruitment of immune cells that drive adaptive immune responses. Here, we examined whether the clinically successful adjuvants MF59/AddaVax could be used for subcutaneous use and how antigen delivery can be synergized with cellular dynamics at the vaccination site. Subcutaneous injection of AddaVax leads to thickening of the skin, characterized by a neutrophil‐monocyte recruitment sequence. Skin‐infiltrating CCR2+Ly6Chigh monocytes showed differentiation to CD11b+Ly6C+MHCII+CD11c+CD64+ monocyte‐derived DCs over time in the hypodermal layers of the skin, expressing high levels of CD209a/mDC‐SIGN. Surprisingly, skin thickening was accompanied with increased white adipose tissue highly enriched with monocytes. Analysis of the skin‐draining lymph nodes revealed early increases in neutrophils and moDCs at 12 hours after injection and later increases in migratory cDC2s. Subcutaneous vaccination with AddaVax enhanced antigen‐specific CD8+ and CD4+ T cell responses, while moDC targeting using antigen‐coupled CD209a antibody additionally boosted humoral responses. Hence, oil‐in‐water emulsions provide an attractive immune modulatory adjuvants aimed at increasing cellular responses, as well as antibody responses when combined with moDC targeting.

中文翻译：

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角鲨烯基水包油佐剂皮下免疫后的免疫动力学

临床上成功的佐剂 MF59 用于季节性流感疫苗，建议通过在肌肉中创造具有免疫能力的微环境来增强免疫力，从而允许招募驱动适应性免疫反应的免疫细胞。在这里，我们检查了临床上成功的佐剂 MF59/AddaVax 是否可用于皮下使用，以及抗原递送如何与疫苗接种部位的细胞动力学协同作用。AddaVax 的皮下注射导致皮肤增厚，其特征是中性粒细胞-单核细胞募集序列。皮肤浸润的 CCR2+Ly6Chigh 单核细胞随着时间的推移在皮肤的皮下层中分化为 CD11b+Ly6C+MHCII+CD11c+CD64+ 单核细胞衍生的 DC，表达高水平的 CD209a/mDC-SIGN。出奇，皮肤增厚伴随着富含单核细胞的白色脂肪组织增加。对皮肤引流淋巴结的分析显示，注射后 12 小时中性粒细胞和 moDCs 早期增加，随后迁移 cDC2s 增加。AddaVax 皮下疫苗接种增强了抗原特异性 CD8+ 和 CD4+ T 细胞反应，而使用抗原偶联 CD209a 抗体靶向 moDC 还增强了体液反应。因此，水包油乳液提供了一种有吸引力的免疫调节佐剂，旨在增加细胞反应，以及与 moDC 靶向结合时的抗体反应。AddaVax 皮下接种增强了抗原特异性 CD8+ 和 CD4+ T 细胞反应，而使用抗原偶联 CD209a 抗体靶向 moDC 还增强了体液反应。因此，水包油乳液提供了一种有吸引力的免疫调节佐剂，旨在增加细胞反应，以及与 moDC 靶向结合时的抗体反应。AddaVax 皮下接种增强了抗原特异性 CD8+ 和 CD4+ T 细胞反应，而使用抗原偶联 CD209a 抗体靶向 moDC 还增强了体液反应。因此，水包油乳液提供了一种有吸引力的免疫调节佐剂，旨在增加细胞反应，以及与 moDC 靶向结合时的抗体反应。