Phase II STTR development of an intranasal/oral Spirulina-based PfCSP malaria vaccine.

基于螺旋藻的 PfCSP 疟疾疫苗的鼻内/口服 STTR 开发的 II 期。

基本信息

批准号：
10325170
负责人：
Nhi Khuong
金额：
$ 100万
依托单位：
LUMEN BIOSCIENCE, INC.
依托单位国家：
美国
项目类别：
财政年份：
2018
资助国家：
美国
起止时间：
2018-05-17 至 2025-06-30
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10325170
关键词：
Antibodies Antibody Response Antigens Attenuated Biological Sciences Blocking Antibodies Capital Financing Capsid Proteins Clinic Clinical Trials Clinical trial protocol document Cloning Cold Chains Complex Consumption Cyanobacterium Department of Defense Department of Energy Development Development Plans Dose Dyes Engineering Epitopes Falciparum Malaria Female Fishes Food Formulation Foundations Future Genetic Genetic Engineering Goals Grant Health Personnel Hepatitis B Virus Human Human Papillomavirus Immune response Immunoglobulin G Inbred Strains Mice Infection prevention Intervention Laboratories Legal patent Logistics Malaria Malaria Vaccines Medical Medical Waste Methodology Modeling Morbidity - disease rate Mucous Membrane Mus Needles Nutritional Oral Oral Poliovirus Vaccine Pain Parasites Phase Plasmodium Plasmodium falciparum Plasmodium vaccine Process Production Proteins Recombinants Regimen Rodent Role Route Safety Savings Series Small Business Technology Transfer Research Source Spirulina preparation Sporozoites Subunit Vaccines Syringes System Technology Training Universities Vaccination Vaccine Design Vaccines Viral Virus-like particle Washington Woodchuck Hepatitis B Virus base circumsporozoite protein clinical development combat cost cost effective design disability first-in-human immunogenic immunogenicity improved inhibiting antibody male meetings mouse model non-compliance nonhuman primate oral vaccine pathogen pre-clinical protein expression response success vaccine delivery vaccine evaluation

项目摘要

ABSTRACT Vaccination represents the single most effective and cost‐effective medical intervention devised to date, saving lives and reducing morbidity and disability for billions of humans. Despite the early success of the oral polio vaccine, most vaccines are delivered parenterally, and as such are associated with pain, non‐compliance, biohazardous medical waste and the need for trained medical personnel. Moreover, strict requirements for production, transport and storage logistics (the “cold chain”) are costly and present substantial logistical challenges. Mucosal (oral, intranasal, etc.) vaccine strategies eliminate or significantly reduce these drawbacks. The potential use of Arthrospira platensis (commonly called spirulina) as an oral vaccine delivery platform is highly attractive, given its safety profile, rich nutritional content and wide acceptance as a human food source. Lumen Bioscience has developed unique, patented technology to genetically engineer spirulina to express heterologous proteins. Lumen Bioscience's spirulina vaccine platform consists of recombinant strains designed to express viral capsid proteins that assemble and form durable high‐order complexes commonly called virus‐like particles (VLPs). Parenterally‐administered VLP‐based vaccines have been used in humans for prevention of infections with human papilloma virus, hepatitis B virus, and malaria parasites. Intranasally and orally‐ administered spirulina‐expressed VLPs have been engineered to efficiently express pathogen‐derived antigens inserted into the exterior‐facing VLP domains. Here, VLPs bearing epitopes derived from Plasmodium falciparum circumsporozoite protein (CSP) in spirulina will be administered intranasally and orally to mice and non‐human primates. This approach has been shown to induce systemic anti‐CSP IgG, which confers protection against sporozoite challenge in mouse models. This project aims to optimize and develop the intranasal/oral spirulina vaccine model as a safe and effective malaria vaccine using mice and non‐human primate models to enable a future transition to the clinic.

抽象的疫苗接种是迄今为止设计的最有效和最具成本效益的医疗干预措施，可以挽救生命和尽管口服脊髓灰质炎疫苗取得了早期成功，但大多数人还是减少了发病率和残疾。疫苗是肠胃外给药的，因此会带来疼痛、不合规、生物危害性医疗废物而且需要训练有素的医务人员，而且对生产、运输和储存都有严格的要求。物流（“冷链”）成本高昂，并且对粘膜（口服、鼻内等）疫苗带来巨大的物流挑战。策略消除或显着减少这些缺点。钝顶节旋藻（通常称为节旋藻）的潜在用途。螺旋藻）作为口服疫苗输送平台非常有吸引力，因为它的安全性、丰富的营养成分和 Lumen Bioscience 已开发出独特的基因专利技术，已被广泛接受为人类食物来源。 Lumen Bioscience 的螺旋藻疫苗平台由以下部分组成：重组菌株旨在表达病毒衣壳蛋白，组装并形成持久的高阶复合物通常称为病毒样颗粒 (VLP) 的肠外注射 VLP 疫苗已用于人类。预防鼻内和口腔感染人乳头状瘤病毒、乙型肝炎病毒和疟疾寄生虫。施用的螺旋藻表达的 VLP 已被设计为有效表达插入的病原体衍生抗原此处，VLP 带有源自恶性疟原虫的表位。螺旋藻中的环子孢子蛋白（CSP）将通过鼻内和口服给药于小鼠和非人类灵长类动物。这种方法已被证明可以诱导全身性抗 CSP IgG，从而提供针对子孢子攻击的保护作用。该项目旨在优化和开发鼻内/口服螺旋藻疫苗模型，使其成为一种安全且可靠的模型。使用小鼠和非人类灵长类动物模型开发有效的疟疾疫苗，以实现未来向临床的过渡。