Sublingual Supramolecular Vaccines and Immunotherapies

即使疫苗发展迅速并被证明是有效和安全的，疫苗接种 竞选活动继续受到公众犹豫不决和公平分发疫苗的挑战的阻碍 在全球各地。疫苗犹豫不决，即个人拒绝或推迟接种疫苗，一直是一种持久的现象 挑战，影响到美国和全球三分之一到四分之一的个人。不公平地，它影响到种族和 少数民族社区尤为强烈，并在2019年被世界卫生组织命名为疫苗 犹豫不决是全球健康的十大威胁之一。针头注射，增加疫苗接种 反应性，是疫苗迟疑的一个重要驱动因素。公平的第二个基本障碍 疫苗的可获得性涉及分销链。大多数疫苗必须运输和储存在 防止效力丧失的持续冷链，使全球分销具有挑战性。面对这些 限制、血统导向或其他多剂量策略，涉及跨区域连续递送抗原 对于目前缺乏的一系列疾病，几周或几个月的科学兴趣越来越大 然而，疫苗的全球分配和患者接受度的问题随着 反复给药。该项目寻求利用工程化超分子多肽生物材料疫苗 特别是为舌下途径提供有效的疫苗接种。该项目旨在设计一种货架- 稳定、易于管理且产生最小反应的疫苗平台，可替代针头疫苗 疫苗依赖于连续冷藏。我们将建立在创新的自组装肽的基础上 我们小组和其他人最近推出的平台，以阐明最大化实现 以及调整舌下疫苗接种反应。在前期工作中，我们已经建立了- 基于片剂的超分子疫苗技术--超分子免疫 舌下肽(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，使用多因素实验设计(DOE)方法来确定超分子大小， 电荷、粘附性和佐剂络合作用影响淋巴转运和体液和 小鼠模型中的舌下语细胞反应。将为流感建立关键的概念验证， 寨卡病毒和HIV-1病毒。最后，将建立SIMPL作为多剂量世系定向疫苗接种的基础。 老鼠和兔子。我们的协作团队因靠近普拉特工程学院和 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 生物工程师和生物材料专家(科利尔实验室)和免疫学家和疫苗专家(福达实验室)。

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).