An in-situ gelling nasal vaccine delivery platform

原位胶凝鼻疫苗递送平台

• 批准号: 6739349
• 负责人: Yawei Ni
• 金额: $ 42.49万
• 依托单位: DELSITE BIOTECHNOLOGIES, INC.
• 依托单位国家: 美国
• 财政年份: 2004
• 资助国家: 美国
• 起止时间: 2004-03-01 至 2006-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6739349
• 关键词: SDS polyacrylamide gel electrophoresis; active immunization; antigens; biotechnology; drug administration routes; drug delivery systems; enzyme linked immunosorbent assay; high performance liquid chromatography; humoral immunity; immune response; immunity; immunoglobulin A; immunoglobulin G; immunologic substance development /preparation; laboratory mouse; mucosal immunity; tissue /cell culture; vaccines

DESCRIPTION (provided by applicant): The nasal cavity represents an easily accessible and effective route of vaccination by which not only systemic, but also mucosal immunity, can be induced. Nasal vaccination is easy to administer and is suitable for mass immunization. New and existing vaccines can potentially be delivered via this route. The overall goal is to develop a simple and broad nasal vaccine delivery platform that prolongs the antigen residence time, enhances immune response, provides an easy formulation process, and is suitable for many different types of antigens. This platform, trademarked as GelVac, is based on a unique high molecular weight acidic polysaccharide (GelSite TM polymer). The GelSite polymer is capable of gelling in-situ, or changing from liquid to a gel upon contact with nasal fluids, thereby providing a controlled release of the antigen. Preliminary studies have provided an initial proof-of-concept for the GelVac platform by demonstrating in situ gelling in the nasal cavity, prolonged nasal residence, and increased serum IgG and lung IgA immune response against a model antigen (DT-CRM, diphtheria toxin mutant CRM) following intranasal delivery. This proposal seeks to establish the GelVac platform by determining its basic functional properties in relation to its effect on immune response and protection. Specifically, this study will examine and determine 1) the nasal residence times of the gel and antigen, 2) factors affecting antigen release, 3) formulation parameters for different antigens, and 4) immune response and protection following intranasal delivery in the presence or absence of an adjuvant. The feasibility of this platform as a broad nasal vaccine delivery vehicle will be demonstrated using different types of antigens including proteins (DT-CRM and tetanus toxoid), polysaccharide-protein conjugate (Haemophilus influenzae b polysaccharide-protein conjugate), and viral particles (rotavirus and influenza virus). These studies will form the basis for phase II development of this platform targeting demonstration of safety and efficacy against selected pathogens that have significant unmet medical and biodefense needs in humans.

描述（由申请方提供）：鼻腔代表了一种容易获得的有效接种途径，不仅可以诱导全身免疫，还可以诱导粘膜免疫。鼻腔接种易于管理，适用于大规模免疫。新的和现有的疫苗可能通过这一途径提供。总体目标是开发一种简单而广泛的鼻腔疫苗递送平台，其缩短抗原停留时间，增强免疫应答，提供简单的配制过程，并且适用于许多不同类型的抗原。这个平台，商标为GelVac，是基于一个独特的高分子量酸性多糖（GelSite TM聚合物）。GelSite聚合物能够原位胶凝，或在与鼻液接触时从液体变为凝胶，从而提供抗原的受控释放。 初步研究通过证明鼻内给药后在鼻腔中原位胶凝、延长鼻腔驻留以及针对模型抗原（DT-CRM，白喉毒素突变体CRM）的血清IgG和肺IgA免疫应答增加，为GelVac平台提供了初步概念验证。该提案旨在通过确定GelVac平台与其对免疫应答和保护作用相关的基本功能特性来建立GelVac平台。具体而言，本研究将检查和确定1）凝胶和抗原的鼻滞留时间，2）影响抗原释放的因素，3）不同抗原的制剂参数，以及4）在存在或不存在佐剂的情况下鼻内递送后的免疫应答和保护。将使用不同类型的抗原，包括蛋白质（DT-CRM和破伤风类毒素）、多糖-蛋白质缀合物（流感嗜血杆菌B多糖-蛋白质缀合物）和病毒颗粒（轮状病毒和流感病毒），证明该平台作为广泛鼻疫苗递送载体的可行性。这些研究将成为该平台第二阶段开发的基础，旨在证明对人类医疗和生物防御需求显著未满足的选定病原体的安全性和有效性。