Engineering a Nanoscale Al-MOF-Armored Antigen Carried by a “Trojan Horse”-Like Platform for Oral Vaccination to Induce Potent and Long-Lasting Immunity

Abstract

Vaccination via the oral administration of an antigen faces many challenges, including gastrointestinal (GI) proteolysis and mucosal barriers. To limit GI proteolysis, a biomimetically mineralized aluminum-based metal–organic framework (Al-MOF) system that is resistant to ambient temperature and pH and can act synergistically as a delivery vehicle and an adjuvant is synthesized over a model antigen ovalbumin (OVA) to act as armor. To overcome mucosal barriers, a yeast-derived capsule is used to carry the Al-MOF-armored OVA as a “Trojan Horse”-like transport platform. In vitro experiments reveal that the mineralization of Al-MOFs forms an armor on OVA that protects against highly acidic and degradative GI conditions. However, the mineralized Al-MOFs can gradually disintegrate in a phosphate ion-containing simulated intracellular fluid, slowly releasing their encapsulated OVA. In vivo studies reveal that the “Trojan Horse”-like transport platform specifically targets intestinal M cells, favoring the transepithelial transport of the Al-MOF-armored OVA, followed by subsequent endocytosis in local macrophages, ultimately accumulating in mesenteric lymph nodes, yielding long-lasting, high-levels of mucosal S-IgA and serum IgG antibodies. Such an engineered delivery platform may represent a promising strategy for the oral administration of prophylactic or therapeutic antigens for vaccination.