Sublingual Supramolecular Vaccines and Immunotherapies

舌下超分子疫苗和免疫疗法

• 批准号: 10671694
• 负责人: Joel H Collier
• 金额: $ 43.75万
• 依托单位: DUKE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-09-20 至 2026-08-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10671694
• 关键词: Adhesives; Adjuvant; Affect; Allergic; Antibody Response; Antigens; Articulation; Attention; Autoimmune Diseases; B-Lymphocytes; Biocompatible Materials; Biomedical Engineering; Charge; Child; Cold Chains; Communicable Diseases; Disease; Distress; Dose; Engineering; Epitopes; Equity; Experimental Designs; Face; Glycoproteins; HIV-1; Human; Immune response; Immunization; Immunologist; Immunotherapeutic agent; Immunotherapy; Individual; Inequity; Inflammatory; Influenza; Injections; Investigation; Lymphatic; Lymphoid Tissue; Malignant Neoplasms; Modeling; Modification; Molecular; Mucins; Mucous Membrane; Mus; Names; Needles; Oral mucous membrane structure; Oryctolagus cuniculus; Pain; Pain Free; Patients; Penetration; Peptides; Polymers; Protein Fragment; Proteins; Public Health; RNA vaccine; Refrigeration; Regimen; Route; STING agonists; Schools; Shapes; Specialist; Surface; System; T-Lymphocyte Epitopes; Tablets; Technology; Temperature; Tongue; Vaccination; Vaccines; Work; World Health Organization; ZIKA; design; ethnic minority; global health; immunoengineering; immunogenic; improved; innovation; interest; minority communities; molecular assembly/self assembly; mouse model; nanofiber; novel vaccines; peptide vaccination; physical property; prevent; racial minority; response; self assembly; success; trafficking; vaccination strategy; vaccine access; vaccine distribution; vaccine hesitancy; vaccine platform

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).

即使疫苗快速开发并证明是有效且安全的，疫苗接种的 公众的犹豫和挑战公平分发疫苗的挑战仍然受到阻碍 全球。疫苗犹豫不决（个人拒绝或延迟疫苗接种）一直是持久的 挑战，影响美国和全球四分之一至四分之一的人。不公平地影响种族和 少数民族社区特别强烈，在2019年，世界卫生组织名为疫苗 犹豫不决是对全球健康的最高威胁之一。基于针的注射，增加疫苗 反应生成性是疫苗犹豫的重要驱动力。公平的第二个基本障碍 疫苗的可用性涉及分布链。大多数疫苗必须在 连续的冷链，以防止效力损失，使全球分布具有挑战性。面对这些 限制，谱系定向或其他多剂量策略，涉及抗原在 数周或几个月正在接受越来越多的科学兴趣，目前缺乏一系列疾病 疫苗，但是全球分配和患者接受的问题在指数上更具挑战性 重复给药。该项目旨在利用经过设计的超分子肽生物材料疫苗 专门用于舌下途径，以提供有效的疫苗接种。该项目旨在设计一个架子 - 稳定，易于给药和微型反应疫苗平台作为基于针的替代品 依赖连续制冷的疫苗。我们将基于创新的自组装肽 我们小组和其他人最近引入的平台是为了阐明最大化所必需的因素 并调整舌下疫苗接种反应。在初步工作中，我们建立了证明 基于片剂的超分子疫苗接种技术的概念，超分子免疫 舌下肽（简单），但要调整强度和质量的关键设计参数 免疫反应尚待阐明。因此，该项目的目的是阐明这些设计 规则，使用多因素设计的设计（DOE）方法来确定超分子的大小， 电荷，粘附性和辅助络合能影响淋巴运输和体液， 小鼠模型中的蜂窝响应。将为流感的关键概念证明， Zika和HIV-1。最后，将建立简单作为多剂量谱系指导疫苗接种的基础 老鼠和兔子。普拉特工程学院和 公爵人类疫苗研究所（DHVI），提供了一个独特的机会来结合观点 生物工程师和生物材料专家（Collier Lab）以及免疫学家和疫苗专家（Fouda Lab）。