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

摘要 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， 降低数十亿人的发病率和残疾率。尽管口服脊髓灰质炎疫苗取得了早期的成功， 疫苗是通过胃肠外途径接种的，因此与疼痛、不依从、生物危害性医疗废物有关 以及对训练有素的医务人员的需求。此外，严格的生产、运输和储存要求 物流（“冷链”）成本高昂，并带来了巨大的物流挑战。粘液（口服、鼻内等）疫苗 战略消除或显著减少了这些缺点。钝顶节旋藻（通常称为 螺旋藻）作为口服疫苗递送平台是非常有吸引力的，因为其安全性、丰富的营养含量和 被广泛接受为人类的食物来源。Lumen Bioscience开发了独特的专利技术， 改造螺旋藻以表达异源蛋白。Lumen Bioscience的螺旋藻疫苗平台包括 设计用于表达病毒衣壳蛋白的重组菌株，所述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）。胃肠外施用的基于VLP的疫苗已用于人类， 预防人乳头瘤病毒、B型肝炎病毒和疟疾寄生虫感染。鼻内和口服- 施用的螺旋藻表达的VLP已经被工程化以有效地表达插入的病原体来源的抗原。 进入面向外部的VLP领域在此，携带来源于恶性疟原虫的表位的VLP 螺旋藻中的环子孢子蛋白（CSP）将鼻内和口服给予小鼠和非人灵长类动物。 这种方法已被证明可以诱导全身性抗CSP IgG，其可以保护小鼠免受子孢子攻击。 小鼠模型。本项目旨在优化和开发鼻内/口服螺旋藻疫苗模型， 使用小鼠和非人灵长类动物模型的有效疟疾疫苗，以便将来过渡到临床。

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.