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单一医疗干预措施，拯救生命和 减少数十亿人的发病率和残疾。尽管口服脊髓灰质炎疫苗取得了早期的成功，但大多数 疫苗是非肠道注射的，因此与疼痛、不合规、生物危险的医疗废物有关 以及对训练有素的医务人员的需求。此外，对生产、运输和储存的严格要求 物流(“冷链”)成本高昂，并带来巨大的物流挑战。粘膜(口腔、鼻腔等)疫苗 战略消除或显著减少了这些缺点。节旋藻的潜在用途(俗称 螺旋藻)作为口服疫苗递送平台非常有吸引力，因为它的安全性、丰富的营养成分和 被广泛接受为人类食物来源。Lumen Bioscience已经开发出独特的专利技术来从基因上 工程螺旋藻表达异源蛋白质。Lumen Bioscience的螺旋藻疫苗平台包括 设计表达病毒衣壳蛋白的重组菌株，这些病毒衣壳蛋白可以组装并形成持久的高阶复合体 通常被称为病毒样颗粒(VLP)。基于VLP的非肠道注射疫苗已用于人类 预防感染人乳头瘤病毒、乙肝病毒和疟疾寄生虫。鼻腔和口腔- 注射螺旋藻表达的VLP已经被设计成有效地表达插入的病原体来源的抗原 进入面向外部的VLP域。在这里，携带恶性疟原虫抗原表位的VLP 螺旋藻中的环子孢子蛋白(CSP)将被滴鼻和口服给小鼠和非人类灵长类动物。 这种方法已被证明能诱导系统抗CSP Ig G，从而提供对子孢子攻击的保护作用 老鼠模型。本项目旨在优化和发展鼻腔/口服螺旋藻疫苗模型，作为一种安全和 使用小鼠和非人类灵长类动物模型的有效疟疾疫苗，使未来能够过渡到临床。

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.