Sublingual Supramolecular Vaccines and Immunotherapies

即使疫苗被迅速开发出来并被证明是有效和安全的， 由于公众的犹豫和公平分配疫苗的挑战， 环绕地球仪。疫苗犹豫，即个人拒绝或推迟接种疫苗，一直是一个持久的问题。 这一挑战影响了美国和全球三分之一到四分之一的人。不公平的是，它影响到种族和 少数民族社区尤其强烈，2019年，世界卫生组织将疫苗命名为 犹豫是全球健康的十大威胁之一。针式注射，增加了疫苗 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 一个连续的冷链，以防止效力损失，使全球分销具有挑战性。面对这些 局限性，谱系定向或其他多剂量策略，涉及抗原的顺序递送， 几周或几个月的时间里，科学界对目前缺乏的一系列疾病越来越感兴趣。 疫苗，但全球分配和患者接受的问题是指数更具挑战性， 重复给药。本项目旨在利用超分子肽生物材料疫苗工程 特别是舌下途径，以提供有效的疫苗接种。该项目旨在设计一个架子- 稳定、易于给药且反应原性最低的疫苗平台，作为基于针头的疫苗的替代品 疫苗需要持续冷藏。我们将在创新的自组装肽的基础上 我们小组和其他人最近介绍的平台，以阐明最大化 和调节舌下接种反应。在初步工作中，我们已经建立了证据- 基于片剂的超分子疫苗接种技术的概念， 肽舌下（SIMPL），但调整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，使用多因子实验设计（DOE）方法来确定超分子大小， 电荷、粘膜粘附性和佐剂复合影响淋巴运输和体液， 在小鼠模型中的舌下细胞反应。将为流感建立关键的概念验证， 寨卡病毒和HIV-1。最后，SIMPL将被确立为多剂量谱系定向疫苗接种的基础， 老鼠和兔子我们的合作团队是由工程的普拉特学校附近促进， 杜克人类疫苗研究所（DHVI），提供了一个独特的机会，联合收割机的观点， 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).