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.