Vaccine adjuvants are thought to work by stimulating innate immunity in the draining lymph node (LN), although this has not been proven in humans. To bridge the data obtained in animals to humans, we have developed an in situ human LN explant model to investigate how adjuvants initiate immunity. Slices of explanted LNs were exposed to vaccine adjuvants and revealed responses that were not detectable in LN cell suspensions. We used this model to compare the liposome-based AS01 with its components, monophosphoryl lipid A (MPL) and QS-21, and TLR ligands. Liposomes were predominantly taken up by subcapsular sinus–lining macrophages, monocytes, and DCs. AS01 induced DC maturation and a strong proinflammatory cytokine response in intact LN slices but not in dissociated cell cultures, in contrast to R848. This suggests that the onset of the immune response to AS01 required a coordinated activation of LN cells in time and space. Consistent with the robust immune response observed in older adults with AS01-adjuvanted vaccines, the AS01 response in human LNs was independent of age, unlike the response to R848. This human LN explant model is a valuable tool for studying the mechanism of action of adjuvants in humans and for screening new formulations to streamline vaccine development.

中文翻译：

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在人淋巴结外植体中，辅助 AS01 的先天免疫细胞激活与年龄无关


疫苗佐剂被认为通过刺激引流淋巴结 （LN） 的先天免疫起作用，尽管这尚未在人类中得到证实。为了将动物与人类获得的数据联系起来，我们开发了一种原位人类 LN 外植体模型来研究佐剂如何启动免疫。将外植体 LN 的切片暴露于疫苗佐剂中，并揭示了在 LN 细胞悬液中无法检测到的反应。我们用这个模型来比较基于脂质体的 AS01 与其成分单磷酸酯脂质 A （MPL） 和 QS-21 以及 TLR 配体。脂质体主要被包膜下窦衬里的巨噬细胞、单核细胞和 DC 摄取。与 R848 相比，AS01 在完整的 LN 切片中诱导 DC 成熟和强烈的促炎细胞因子反应，但在解离的细胞培养物中则不诱导。这表明对 AS01 的免疫反应的开始需要 LN 细胞在时间和空间上的协调激活。与在老年人使用 AS01 佐剂疫苗中观察到的强烈免疫反应一致，人类 LN 中的 AS01 反应与年龄无关，这与对 R848 的反应不同。这种人类 LN 外植体模型是研究佐剂在人类中的作用机制和筛选新配方以简化疫苗开发的宝贵工具。