As an ingredient of vaccines, adjuvants are indispensable for enhancing and directly inducing robust and extensive adaptive immune responses associated with vaccine antigens. In this study, we initially determined that a new molecular immunopotentiator, ophiopogonin D (OP-D), enhanced the antibody response to antigen. Because OP-D has certain disadvantages, including poor solubility, we next encapsulated OP-D in a nanoemulsion adjuvant (nanoemulsion-encapsulated OP-D, NOD) using low-energy emulsification methods. The NOD thus produced was small, with an average size of 76.45 nm, and exhibited good distribution (PdI value 0.16), significantly increasing the solubility of OP-D. Furthermore, NOD exhibited reduced cellular toxicity and acute toxicity. Our results showed that a fusion antigen of MRSA (HlaH_35LIsdB_348-465) formulated with NOD significantly improved humoral and cellular immune responses compared to those observed in the antigen/OP-D and antigen/AlPO₄ groups. Compared with antigen/OP-D, the antigen formulated with NOD more effectively promoted antigen uptake by dendritic cells (DCs) and the activation of antigen-presenting cells (APCs). Moreover, the NOD-formulated antigen had ideal protective efficacy in a MRSA sepsis model by inducing more potent antibody responses and a Th1/Th17-biased CD4⁺ T cell immune response. Therefore, these results suggest that NOD is a promising and robust adjuvant platform for a MRSA vaccine.

Statement of Significance

The importance of adjuvants to new generation vaccines can be compared with the Prometheus Fire for humans. We first identified a new powerful immunopotentiator, Ophiopogonin D, among dozens of natural products and then used nanotechnology to construct a highly efficient and low toxic adjuvant system (NOD). Our approach intersects natural medicinal chemistry, nanomaterials and immunology, revealing that a strong adjuvant activity of this adjuvant system was verified in vitro and in vivo, and the application of MRSA subunit vaccine model for survival experiments achieved a 100% protection rate. This research illustrate that NOD is a promising and robust adjuvant platform for subunit vaccines.

中文翻译：

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封装在纳米乳剂中的免疫增强剂ophiopogonin D作为增强疫苗效力的强大佐剂

作为疫苗的成分，佐剂对于增强和直接诱导与疫苗抗原相关的强大而广泛的适应性免疫应答是必不可少的。在这项研究中，我们最初确定了一种新的分子免疫增强剂，ophophogonin D（OP-D），可以增强对抗原的抗体反应。因为OP-D具有某些缺点，包括溶解性差，所以我们接下来使用低能乳化方法将OP-D封装在纳米乳液佐剂（纳米乳液封装的OP-D，NOD）中。这样产生的NOD很小，平均尺寸为76.45nm，并且显示出良好的分布（PdI值为0.16），显着增加了OP-D的溶解度。此外，NOD表现出降低的细胞毒性和急性毒性。我们的结果表明，MRSA（HlaH _35L IsdB与在抗原/ OP-D和抗原/ AlPO ₄组中观察到的相比，用NOD配制的_348-465）显着改善了体液和细胞免疫应答。与抗原/ OP-D相比，用NOD配制的抗原可以更有效地促进树突状细胞（DC）吸收抗原和激活抗原呈递细胞（APC）。此外，通过诱导更有效的抗体反应和偏向Th1 / Th17的CD4 ⁺ T细胞免疫反应，NOD配制的抗原在MRSA脓毒症模型中具有理想的保护功效。因此，这些结果表明，NOD是用于MRSA疫苗的有希望且强大的佐剂平台。

重要声明

佐剂对新一代疫苗的重要性可以与普罗米修斯之火对人类进行比较。我们首先在数十种天然产品中鉴定了一种新型的强大免疫增强剂Ophiopogonin D，然后使用纳米技术构建了一种高效，低毒的佐剂系统（NOD）。我们的方法与天然药物化学，纳米材料和免疫学相交，揭示了该佐剂系统的强大佐剂活性已在体内和体外得到验证，MRSA亚单位疫苗模型在存活实验中的应用获得了100％的保护率。这项研究表明，NOD是用于亚单位疫苗的有前途且强大的佐剂平台。