Sporopollenin Spikes Augment Antigen‐Specific Immune Response and Generate Long‐Lived Humoral Immunity

Oral vaccine delivery remains an unmet goal due to biochemical and immunological barriers in the gastrointestinal tract. Sporopollenin microcapsules from natural pollen grains have recently been engineered to overcome these multifaceted challenges. Using four morphologically different sporopollenin shells and two inbred mouse strains, this study addresses three key questions regarding sporopollenin shell's application for oral vaccine delivery: i) the impact of sporopollenin shell surface morphology on the immune response, ii) the duration of the immunity, and iii) the applicability of the delivery system across a diverse genetic background population. Using ovalbumin (OVA) as a model vaccine antigen, this study demonstrates that OVA can adsorb on the sporopollenin shell surfaces. Mice orally vaccinated with a sporopollenin shell‐based OVA formulation show sustained antibody responses for 454 days after the immunization that are correlated with the generation of OVA‐specific plasma cells in the vaccinated mice bone marrow. Sporopollenin shell surface spikes have a greater impact on immune responses than the shell size and shape. A spiky ragweed sporopollenin formulation induces systemic and mucosal responses in C57BL/6 and BALB/c mice. Together, this study provides a framework to select sporopollenin shells based on the surface morphology to use as a microcapsule for oral vaccination.