Progress in the past quarter-century on understanding the molecular, cellular, and in vivo components of the mucosal immune system have allowed us to develop a practical strategy for a novel mucosal vaccine. The mucosal immune system can induce secretory IgA (SIgA) and serum IgG responses to provide two layers of defense against mucosal pathogens. For SIgA-mediated immunity in the gastrointestinal tract, the gut-associated lymphoid tissue contains both the tissue-dependent and tissue-independent IgA components. Harnessing the mucosal immune system for vaccine development may help prevent the global health problems caused by enteric infectious diseases. We have therefore combined mucosal immunology and plant biology to create a rice-based mucosal vaccine that requires neither needles and syringes nor refrigeration.