Nanoparticle-detained toxins for safe and effective vaccination.

Nanoparticle-detained toxins for safe and effective vaccination.
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DOI:
10.1038/nnano.2013.254
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发表时间:
2013-12
影响因子:
38.3
通讯作者:
--
中科院分区:
材料科学1区
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--
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类毒素疫苗-基于灭活细菌毒素的疫苗-通常用于促进抗毒素免疫以治疗和预防细菌感染。在化学或热变性后,可以施用灭活的毒素以产生毒素特异性免疫应答。然而,在去除毒素毒力的同时保持忠实的抗原呈递仍然是一个主要挑战,并且在类毒素发展中存在功效和安全性之间的权衡。在这里,我们展示了一种基于纳米颗粒的毒素滞留策略,该策略安全地提供用于免疫处理的非破坏性成孔毒素。使用红细胞膜包被的纳米颗粒和葡萄球菌α-溶血素,我们证明了通过自发颗粒截留有效的毒力中和。与用热变性毒素接种相比,用纳米颗粒滞留毒素接种的小鼠显示出针对毒素不良反应的上级保护性免疫。我们发现,非破坏性的解毒方法有利于类毒素疫苗的免疫原性和有效性。我们预计,报告的研究开辟了新的可能性,在制备抗毒素疫苗对许多毒力因素,威胁公众健康。
Toxoid vaccines—vaccines based on inactivated bacterial toxins— are routinely used to promote antitoxin immunity for the treatment and prevention of bacterial infections. Following chemical or heat denaturation, inactivated toxins can be administered to mount toxin-specific immune responses. However, retaining faithful antigenic presentation while removing toxin virulence remains a major challenge and presents a trade-off between efficacy and safety in toxoid development. Here we show a nanoparticle-based toxin-detainment strategy that safely delivers non-disrupted pore-forming toxins for immune processing. Using erythrocyte membrane-coated nanoparticles and staphylococcal α-haemolysin, we demonstrate effective virulence neutralization via spontaneous particle entrapment. As compared to vaccination with heat-denatured toxin, mice vaccinated with the nanoparticle-detained toxin showed superior protective immunity against toxin adverse effects. We find that the non-disruptive detoxification approach benefited the immunogenicity and efficacy of toxoid vaccines. We anticipate the reported study to open new possibilities in the preparation of antitoxin vaccines against the many virulence factors that threaten public health.
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发表时间: 2012-01-24
影响因子: 11.1
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