I-Corps: A Multi-Antigen Vaccine Delivery System for the Effective Induction of Mucosal Immunity

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The broader impact/commercial potential of this I-Corps project is the development of a novel vaccine discovery platform. The COVID-19 pandemic has opened our eyes to the urgent need for technologies capable of effectively delivering vaccines that combat mucosal infections. Mucosal infections, such as influenza and rotavirus, make up more than 70% of the yearly cases of infectious diseases recorded in the US, and more than 50% of all infections worldwide. This high infection rate is because most pathogens either infect mucosal tissues directly or begin their invasion at mucosal sites throughout the body (i.e., the nose, intestines, and mouth). The proposed technology solves the need to effectively deliver vaccines to mucosal tissue, providing a robust immune response, and can be rapidly developed and scaled up to respond to emerging pandemics, saving potentially hundreds of thousands of lives. In addition to being rapid response, the proposed vaccine delivery system can be used with multiple antigens at once, potentially reducing the number of vaccinations required throughout a patient’s lifetime. The proposed vaccine platform is needle-free, allowing it to be administered outside of clinics, reducing the need for highly skilled personnel and administration costs especially in low-income countries.This I-Corps project is based on the development of outer cell membrane vesicles as a vaccine delivery platform. Outer membrane vesicles (OMVs) are spherical lipid bilayers naturally produced by bacteria that possess the ability to modulate the immune system. Previously, OMVs were engineered to display antigens on their exterior surface, thereby acting as a self-adjuvanted vaccine platform that has shown promise in animal models as an injectable vaccine. Further modification of the OMV platform to enable the co-delivery of multiple different antigens has been investigated for its immunological potential in a mouse model. Preliminary work has shown this feature to yield potential benefits for vaccine engineering. Additionally, through buccal vaccination in swine, OMVs were shown to induce robust mucosal immunity, without the need for injection.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.