Biomaterial Approaches for Understanding and Overcoming Immunological Barriers to Effective Oral Vaccinations

Abstract Oral vaccines have the potential to reduce cost, improve compliance, and induce immunity at mucosal surfaces that are the first line of defense against infection. The gastrointestinal tract is highly evolved to efficiently digest and absorb nutrients without eliciting aberrant inflammation. However, these functions also limit the efficacy of immunization by the oral route. While mechanisms responsible for the development of tolerance to fed antigens are being illuminated, the application of materials with precise physiochemical properties and immunomodulatory potential may accelerate understanding of immunity within the gastrointestinal tract. Insight into these immunological mechanisms can inform the design of next‐generation oral vaccines to harness critical functions to elicit immunity. Here, material strategies for oral vaccines and their dual function in understanding and overcoming immunological barriers associated with oral immunization are discussed.