Department of NanoEngineering and Chemical Engineering Program , University of California San Diego , La Jolla , California 92093 , United States.
Nano Lett. 2019 Mar 13;19(3):1914-1921. doi: 10.1021/acs.nanolett.8b05051. Epub 2019 Feb 6.
Vaccination represents one of the most effective means of preventing infectious disease. In order to maximize the utility of vaccines, highly potent formulations that are easy to administer and promote high patient compliance are desired. In the present work, a biomimetic self-propelling micromotor formulation is developed for use as an oral antivirulence vaccine. The propulsion is provided by a magnesium-based core, and a biomimetic cell membrane coating is used to detain and neutralize a toxic antigenic payload. The resulting motor toxoids leverage their propulsion properties in order to more effectively elicit mucosal immune responses. After demonstrating the successful fabrication of the motor toxoids, their uptake properties are shown in vitro. When delivered to mice via an oral route, it is then confirmed that the propulsion greatly improves retention and uptake of the antigenic material in the small intestine in vivo. Ultimately, this translates into markedly elevated generation of antibody titers against a model toxin. This work provides a proof-of-concept highlighting the benefits of active oral delivery for vaccine development, opening the door for a new set of applications, in which biomimetic motor technology can provide significant benefits.
疫苗接种是预防传染病最有效的手段之一。为了最大限度地发挥疫苗的效用,人们希望疫苗具有高效、易于使用和提高患者依从性的特点。在本工作中,开发了一种仿生自推进微马达制剂,用作口服抗病毒疫苗。推进力由基于镁的核心提供,仿生细胞膜涂层用于滞留和中和有毒抗原有效载荷。由此产生的马达类毒素利用其推进特性,更有效地引发黏膜免疫反应。在成功制备出马达类毒素后,研究了其体外摄取特性。当通过口服途径递送至小鼠时,证实推进作用极大地提高了抗原物质在体内小肠中的保留和摄取。最终,这导致针对模型毒素的抗体滴度显著升高。这项工作提供了一个概念验证,强调了主动口服递送在疫苗开发方面的优势,为一系列新的应用打开了大门,其中仿生马达技术可以带来显著的优势。