Sublingual Supramolecular Vaccines and Immunotherapies

即使疫苗得到迅速开发并被证明是有效和安全的，疫苗接种 公众的犹豫不决以及公平分配疫苗方面的挑战继续阻碍了宣传活动 全球各地。个人拒绝或延迟接种疫苗的疫苗犹豫一直是一个持续存在的问题 挑战，影响了美国和全球三分之一到四分之一的人。它不公平地影响种族和 少数民族社区尤其强烈，2019年世界卫生组织将疫苗命名为 犹豫不决被列为全球健康的十大威胁之一。针头注射可增加疫苗接种量 反应原性是疫苗犹豫的重要驱动因素。公平的第二个基本障碍 疫苗的供应涉及分销链。大多数疫苗必须在以下范围内运输和储存： 连续的冷链可防止效力损失，这使得全球分销具有挑战性。面对这些 局限性、谱系导向或其他涉及顺序递送抗原的多剂量策略 数周或数月以来，人们对一系列目前缺乏的疾病的科学兴趣日益浓厚 疫苗，但全球分发和患者接受度问题更具挑战性 重复给药。该项目旨在利用超分子肽生物材料设计疫苗 专门针对舌下途径提供有效的疫苗接种。该项目旨在设计一个货架 稳定、易于管理且反应原性最低的疫苗平台，可替代针头疫苗 依赖持续冷藏的疫苗。我们将以创新的自组装肽为基础 我们小组和其他人最近推出的平台，目的是阐明最大化的必要因素 并调整舌下疫苗接种反应。在前期工作中，我们已经建立了证明- 基于片剂的超分子疫苗接种技术的概念，超分子免疫 肽舌下含服（SIMPL），但调节肽强度和质量的关键设计参数 免疫反应仍有待阐明。因此，该项目的目标是阐明这些设计 规则，使用多因素实验设计（DOE）方法来确定超分子尺寸， 电荷、粘膜粘附性和佐剂络合影响淋巴运输和体液和 小鼠模型中舌下的细胞反应。将为流感建立关键的概念验证， 寨卡病毒和 HIV-1。最后，SIMPL 将被建立为多剂量谱系定向疫苗接种的基础 老鼠和兔子。我们的协作团队因毗邻普拉特工程学院和 杜克人类疫苗研究所 (DHVI)，提供了一个独特的机会来结合来自不同领域的观点 生物工程师和生物材料专家（Collier 实验室）以及免疫学家和疫苗专家（Fouda 实验室）。

Even when vaccines are rapidly developed and shown to be efficacious and safe, vaccination campaigns continue to be hampered by public hesitancy and by challenges distributing vaccines equitably around the globe. Vaccine hesitancy, where individuals refuse or delay vaccination, has been a persistent challenge, affecting a third to a quarter of individuals in the US and globally. Inequitably, it affects racial and ethnic minority communities particularly strongly, and in 2019 the World Health Organization named vaccine hesitancy as one of the top-ten threats to global health. Needle-based injections, which increase vaccine reactogenicity, are a significant driver of vaccine hesitancy. A second fundamental hurdle in equitable availability of vaccines involves the chain of distribution. Most vaccines must be transported and stored within a continuous cold-chain to prevent loss of potency, making global distribution challenging. In the face of these limitations, lineage-directed or other multi-dose strategies involving the sequential delivery of antigens across weeks or months are receiving increasing scientific interest towards a range of diseases currently lacking vaccines, yet the issues of global distribution and patient acceptance are exponentially more challenging with repeated dosing. This project seeks to utilize supramolecular peptide biomaterial vaccines engineered specifically for the sublingual route to provide for effective vaccination. The project aims to design a shelf- stable, easily administered, and minimally reactogenic vaccine platform as an alternative to needle-based vaccines relying on continuous refrigeration. We will build upon the innovative self-assembling peptide platforms recently introduced by our group and others in order to elucidate factors necessary for maximizing and adjusting sublingual vaccination responses. In preliminary work, we have established the proof-of- concept of a tablet-based supramolecular vaccination technology, Supramolecular Immunization with Peptides SubLingually (SIMPL), but the key design parameters for adjusting the strength and quality of immune responses remain to be articulated. Therefore the objective of the project is to articulate these design rules, using multifactorial Design-of-Experiments (DOE) approaches to ascertain how supramolecular size, charge, mucoadhesivity, and adjuvant complexation influences the lymphatic trafficking and humoral and cellular responses sublingually in mouse models. Critical proofs-of-concept will be established for influenza, zika, and HIV-1. Finally, SIMPL will be established as a basis for multi-dose lineage-directed vaccination in mice and rabbits. Our collaborative team is facilitated by the proximity of the Pratt School of Engineering and the Duke Human Vaccine Institute (DHVI), providing a unique opportunity to combine perspectives from Bioengineers and biomaterials specialists (Collier lab) and immunologists and vaccine specialists (Fouda lab).