I-Corps Teams: Programmable Nanotechnology Vaccine Platform for Rapid, On-Demand Production

Massachusetts Institute Of Technology, Cambridge MA

Investigators

Abstract

The broader impact/commercial potential of this I-Corps project is that it offer to standardize vaccines across a broad range of pathogens in an economical way. Typically, depending on the type of pathogen, different vaccine development and manufacturing processes must be employed, resulting in costly technological fragmentation. Having a single technology that is applicable to all pathogens is ideal, as it economically streamlines the development and manufacturing process. The ability to rapidly produce vaccines on-demand and at scale is also important. Conventional vaccine design and manufacturing methods take years to develop and months to produce using cells or eggs. Vaccines that can instead be produced by chemically-defined organic and enzymatic reactions in the absence of any living systems is preferred as it avoids cross-contamination. Moreover, if the components can self-assemble into vaccines upon mixing, the energy requirements and costs are dramatically reduced. With such a technology, new vaccines can be efficiently manufactured quickly to meet patient demand. This I-Corps project further develops a platform for a replicon payload inside the nanoparticle vaccine. The replicon, a large mRNA, possesses the safety and flexibility of conventional mRNA, but is capable of finite self-replication. Antigens specific to a particular disease are encoded into the mRNA replicon. Thus, once injected, the replicon can temporarily turn a patient's cells into a vaccine production factory. A second merit is the delivery system innovation that enables the therapeutic deployment of replicons as a vaccination tool: the dendrimer nanomaterial. Purpose-built for replicons, it is a fully synthetic, chemically-defined system that solves the decades-long challenge of safely delivering replicons intact into the cytoplasm of a patient's cells upon injection. The vaccine nanoparticle efficiently activates the cellular and humoral branches of adaptive immunity without booster injections. A third merit is the ability to perform simultaneous vaccinations. Because of the delivery system's large payload capacity, a variety of different and unique replicons can be co-formulated to immunize patients against multiple diseases at once. A fourth merit is that these vaccines do not require adjuvants, thus improving both tolerability and safety.