To improve innate defense against diseases, vaccine formulations are routinely administered to mount immune responses against disease-causing organisms or their associated toxins. These formulations are typically prepared with weakened forms of microbes, their surface proteins, or their virulence factors, which can train the immune system to recognize and neutralize similar infectious threats in later exposures. Owing to many unique properties of nanoparticles in enhancing vaccine potency, nanoscale carriers are drawing increasing interest as a platform for developing safer and more effective vaccine formulations. Notably, a nanoparticle-based strategy was recently demonstrated to safely deliver intact, non-denatured protein toxins to mount a potent anti-toxin immune response. A biomimetic nanoparticle cloaked in biological membranes was used to sequester membrane-active toxins. Upon interaction with the nanoparticles, the toxins become retrained and lose their toxicity as they are precluded from interacting with cellular targets. The resulting particle/toxin complex adopts a nanoparticulate morphology that facilitates the toxins' intracellular delivery. This sequestration approach has immense immunological implications owing to its ability in enabling structurally preserved toxins for immune processing. This technique offers opportunities in novel toxoid vaccine designs that promise more effective anti-toxin immune responses and contrasts the existing paradigm in toxoid preparation, in which toxins are antigenically altered to ensure virulence removal. The potent nanotoxoid formulations provide a viable anti-virulence measure in combating microbial infections that involve membrane-damaging toxins, including methicillin-resistant Staphylococcus aureus (MRSA) and Group A streptococcal infections.

中文翻译：

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纳米类毒素疫苗

为了提高对疾病的先天防御，通常会使用疫苗制剂来激发针对致病生物或其相关毒素的免疫反应。这些制剂通常是用弱化形式的微生物、它们的表面蛋白或它们的毒力因子制备的，它们可以训练免疫系统在以后的暴露中识别和中和类似的感染威胁。由于纳米颗粒在增强疫苗效力方面的许多独特特性，纳米载体作为开发更安全、更有效的疫苗制剂的平台越来越受到关注。值得注意的是，最近证明了一种基于纳米粒子的策略可以安全地递送完整的、非变性的蛋白质毒素，以产生有效的抗毒素免疫反应。隐藏在生物膜中的仿生纳米颗粒用于隔离膜活性毒素。在与纳米颗粒相互作用后，毒素被重新训练并失去毒性，因为它们被排除在与细胞靶标相互作用之外。由此产生的颗粒/毒素复合物采用纳米颗粒形态，有利于毒素的细胞内递送。这种隔离方法具有巨大的免疫学意义，因为它能够使结构上保存的毒素用于免疫处理。该技术为新型类毒素疫苗设计提供了机会，有望产生更有效的抗毒素免疫反应，并与类毒素制备中的现有范例形成对比，其中毒素被抗原改变以确保去除毒力。