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：
10453802
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/10453802
关键词：
Acceleration Antibodies Antibody Response Antigens Attenuated Biological Sciences Blocking Antibodies Capital Financing Capsid Proteins Clinic Clinical Trials Cloning Cold Chains Complex Consumption Cyanobacterium Department of Defense Department of Energy Development Development Plans Dose Dryness 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 Intranasal Administration Invaded Laboratories Legal patent Logistics Malaria Malaria Vaccines Medical Medical Waste Methodology Modeling Morbidity - disease rate Mucous Membrane Mus Needles Nutritional Oral Oral Administration Oral Poliovirus Vaccine Pain Parasites Phase Plasmodium Plasmodium falciparum Plasmodium vaccine Process Production Proteins Recombinants Regimen Rodent Role Route Safety 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 booster vaccine circumsporozoite protein clinical development clinical trial protocol combat cost cost effective design disability first-in-human immunogenic immunogenicity improved inhibiting antibody male mouse model non-compliance nonhuman primate oral vaccine parenteral administration pathogen pre-Investigational New Drug meeting pre-clinical protein expression response safety assessment success vaccine delivery vaccine evaluation vaccine platform vaccine strategy

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.

抽象的疫苗接种代表迄今为止设计的最有效，最具成本效益的医疗干预措施，挽救生命和减少数十亿人类的发病率和残疾。尽管口服脊髓灰质炎疫苗的早期成功，但大多数疫苗是养生的，因此与疼痛，不合规，生化医疗废物有关以及对训练有素的医务人员的需求。此外，生产，运输和存储的严格要求物流（“冷链”）是昂贵的，并带来了重大的后勤挑战。粘膜（口服，鼻内等）疫苗策略消除或显着减少了这些弊端。关节螺旋藻的潜在用途（通常称为）螺旋藻）作为口服疫苗输送平台，鉴于其安全性，丰富的营养含量和广泛接受为人类食物来源。 Lumen Bioscience已开发了独特的专利技术来遗传工程师螺旋藻表达异源蛋白质。 Lumen Bioscience的螺旋藻疫苗平台包括重组菌株旨在表达组装和形成耐用高阶复合物的病毒式衣壳蛋白通常称为病毒样颗粒（VLP）。人类已使用了基于源自vlp的vlp疫苗的人预防人类乳头瘤病毒，丙型肝炎病毒和疟疾寄生虫感染。鼻内和口头施用的螺旋藻表达的VLP已设计为有效表达插入病原体衍生的抗原进入外部面向VLP域。在这里，源自恶性疟原虫的表位的VLP 螺旋藻中的外孢子岩蛋白（CSP）将在鼻内和口头施用给小鼠和非人类隐私。该方法已显示出诱导全身性抗CSP IgG 鼠标模型。该项目旨在优化和开发鼻内/口服螺旋藻疫苗模型作为安全和使用小鼠和非人类灵长类动物模型有效的疟疾疫苗，以使未来向诊所过渡。