Vaccine Delivery Platform Development

项目1的研究人员将专注于基于以下技术的疫苗投放平台的开发 纳米结构。其目标是增强B细胞对HIV-1gp41MPER的免疫力。具体目标是： 目的1.建立以纳米金为载体的多价抗原递送平台。在这里，我们建议开发一种基于金纳米颗粒(GNP)的疫苗平台，它将不仅能够传递多个抗原副本，而且能够传递免疫效应分子。这个平台相对简单，但我们将能够控制抗原密度、平均表位间距以及抗原和免疫效应分子的化学组成。这个模块化平台被设计为同时向B细胞递送抗原和免疫效应器分子，以诱导最大限度的抗体反应。站台 将使用我们最近开发的一种非常有前途的基于gp41-MPER的抗原来开发。 目的2.建立基于DNA纳米结构的多价抗原递送平台。为此，我们提出了一种基于一维DNA聚合物和二维DNA晶格的新型疫苗平台，该平台既可以传递多个副本的抗原，也可以传递免疫效应分子。这个平台与基于GNP的平台之间的主要区别是，这个平台允许通过可编程的、将DNA寡核苷酸自组装成预定义的聚合物或晶格结构来更精确地控制所有参数。尽管复杂程度的提高增加了一些风险，但成功完成这一目标可能真正 彻底改变以短肽为基础的疫苗的研制过程。 目的3.开发一种靶向传递包裹在纳米粒中的抗原的平台。我们建议开发一种基于可生物降解的聚酸酐纳米颗粒(BPN)的靶向纳米疫苗平台，该平台可以稳定抗原，提供仓库效应，并作为佐剂。BPN的表面将装饰有碳水化合物部分，这些碳水化合物部分与树突状细胞和巨噬细胞上的C型凝集素或甘露糖受体特异性地相互作用。该平台的主要功能是增强辅助性T细胞 反应，这反过来将促进B细胞的反应。

Investigators in Project 1 will focus on the development of vaccine delivery platforms based on nanostructures. The goal is to enhance B cell immunity against HIV-1 gp41 MPER. The specific aims are: Aim 1. To develop a platform for delivering multivalent antigens based on gold nanoparticles. Here, we propose to develop a vaccine platform based on gold nanoparticles (GNP) that will be able to deliver not only multiple copies of antigens, but also immune effector molecules. This platform is relatively simple, but we will be able to control the antigen density, average inter-epitope spacing, and the stoichiomentry of antigens and immune effector molecules. This modular platform is designed to present both the antigen and immune effector molecules to B cells simultaneously to induce maximum antibody response. The platform will be developed using a highly promising gp41-MPER-based antigen we recently developed. Aim 2. To develop a platform for delivering multivalent antigens based on DNA nanostructures. In this Aim, we propose to develop a novel vaccine platform based on 1-D DNA polymer and 2-D DNA lattice that can also deliver multiple copies of antigens as well as immune effector molecules. The major difference between this platform and the one based on GNP is that this one allows more precise control of all of the parameters using programmable, self-assembly of DNA oligonucleotides into a predefined polymer or lattice structure. Although increased sophistication adds some risks, successful completion of this Aim could truly revolutionize the process of formulating vaccines based on short polypeptides. Aim 3. To develop a platform for targeted delivery of antigens encapsulated into nanoparticles. We propose to develop a targeted nanovaccine platform based on biodegradable polyanhydride nanoparticles (BPNs) that can stabilize antigens, provide a depot effect, and serve as an adjuvant. The surface of BPNs will be decorated with carbohydrate moieties that specifically interact with C-type lectins or mannose receptors on dendritic cells and macrophages. The major function of this platform is to enhance helper T cell responses, which in turn will boost B cell response.