Expanding opportunities to engineer mucosal vaccination with biomaterials

Mucosal vaccines are receiving increasing interest both for protecting against infectious diseases and for inducing therapeutic immune responses to treat non-infectious diseases. However, the mucosal barriers of the lungs, gastrointestinal tract, genitourinary tract, nasal, and oral tissues each present unique challenges for constructing efficacious vaccines. Vaccination through each of these mucosae requires transport through the mucus and across specialized epithelia to reach tissue-specific immune cells and lymphoid structures, necessitating finely tuned and multifunctional strategies. Serving as inspiration for mucosal vaccine design, pathogens have evolved elaborate, diverse, and multipronged approaches to penetrate and infect mucosae. This review is focused on biomaterials-based strategies, many inspired by pathogens, for designing mucosal vaccine platforms. Passive and active technologies are discussed, along with the microbial processes that they seek to mimic.