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Suppressing Subcapsular Sinus Macrophages Enhances Transport of Nanovaccines to Lymph Node Follicles for Robust Humoral Immunity.
ACS Nano ( IF 15.8 ) Pub Date : 2020-06-01 , DOI: 10.1021/acsnano.0c02240 Yi-Nan Zhang 1, 2 , Wilson Poon 1, 2 , Elana Sefton 1, 2 , Warren C W Chan 1, 2, 3, 4, 5
ACS Nano ( IF 15.8 ) Pub Date : 2020-06-01 , DOI: 10.1021/acsnano.0c02240 Yi-Nan Zhang 1, 2 , Wilson Poon 1, 2 , Elana Sefton 1, 2 , Warren C W Chan 1, 2, 3, 4, 5
Affiliation
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Nanovaccines need to be transported to lymph node follicles to induce humoral immunity and generate neutralizing antibodies. Here, we discovered that subcapsular sinus macrophages play a barrier role to prevent nanovaccines from accessing lymph node follicles. This is illustrated by measuring the humoral immune responses after removing or functionally altering these cells in the nanovaccine transport process. We achieved up to 60 times more antigen-specific antibody production after suppressing subcapsular sinus macrophages. The degree of the enhanced antibody production is dependent on the nanovaccine dose and size, formulation, and administration time. We further found that pharmacological agents that disrupt the macrophage uptake function can be considered as adjuvants in vaccine development. Immunizing mice using nanovaccines formulated with these agents can induce more than 30 times higher antigen-specific antibody production compared to nanovaccines alone. These findings suggest that altering transport barriers to enable more of the nanovaccine to be delivered to the lymph node follicles for neutralizing antibody production is an effective strategy to boost vaccination.
中文翻译：
抑制荚膜下窦巨噬细胞可增强Nanovaccines向淋巴结滤泡的转运，从而具有较强的体液免疫力。
纳米疫苗需要转运到淋巴结滤泡，以诱导体液免疫并产生中和抗体。在这里，我们发现囊下窦巨噬细胞起着阻止纳米疫苗进入淋巴结滤泡的屏障作用。这是通过在纳米疫苗运输过程中去除或功能性改变这些细胞后测量体液免疫反应来说明的。抑制囊下窦巨噬细胞后，我们的抗原特异性抗体产量提高了60倍。抗体产生的增强程度取决于纳米疫苗的剂量和大小，制剂和给药时间。我们进一步发现，破坏巨噬细胞摄取功能的药理剂可被视为疫苗开发中的佐剂。与单独使用纳米疫苗相比，使用由这些试剂配制的纳米疫苗对小鼠进行免疫可诱导的抗原特异性抗体生产高出30倍以上。这些发现表明，改变运输障碍以使更多的纳米疫苗能够被递送至淋巴结滤泡以中和抗体的产生，是加强疫苗接种的有效策略。
更新日期：2020-06-01
中文翻译：
抑制荚膜下窦巨噬细胞可增强Nanovaccines向淋巴结滤泡的转运，从而具有较强的体液免疫力。
纳米疫苗需要转运到淋巴结滤泡，以诱导体液免疫并产生中和抗体。在这里，我们发现囊下窦巨噬细胞起着阻止纳米疫苗进入淋巴结滤泡的屏障作用。这是通过在纳米疫苗运输过程中去除或功能性改变这些细胞后测量体液免疫反应来说明的。抑制囊下窦巨噬细胞后，我们的抗原特异性抗体产量提高了60倍。抗体产生的增强程度取决于纳米疫苗的剂量和大小，制剂和给药时间。我们进一步发现，破坏巨噬细胞摄取功能的药理剂可被视为疫苗开发中的佐剂。与单独使用纳米疫苗相比，使用由这些试剂配制的纳米疫苗对小鼠进行免疫可诱导的抗原特异性抗体生产高出30倍以上。这些发现表明，改变运输障碍以使更多的纳米疫苗能够被递送至淋巴结滤泡以中和抗体的产生，是加强疫苗接种的有效策略。
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