Cyclic di-(3',5')-guanosine monophosphate loaded metal organic frameworks for mucosal immunization against giardiasis

Summary

Giardiasis, caused by the intestinal parasite Giardia lamblia, has no approved human vaccine, and effective adjuvants for gut mucosal immunization have been lacking. This study asked whether a nanoparticle vaccine could deliver a potent adjuvant together with many parasite antigens at once. In mice, the cyclic dinucleotide CDG given intranasally with the single defined antigen α1-giardin protected as well as the standard but human-toxic cholera toxin adjuvant, while curdlan, colforsin, and CpG did not. The authors then made metal-organic framework nanoparticles loaded with CDG and coated with G. lamblia membranes; the particles were ~150–160 nm, released CDG gradually, matured dendritic cells, and after two or three intranasal doses elicited parasite-specific IgG and left 85% of mice with no detectable trophozoites after infection, better than α1-giardin plus soluble CDG. Protection was lost in STING-deficient mice and after CD4 T-cell depletion, was unaffected by IgA deficiency, and did not occur with a non-STING-activating control dinucleotide or when the vaccine was given orally or systemically. The findings identify CDG as an effective mucosal adjuvant and support further development of membrane-coated MOF nanovaccines for mucosal pathogens, although the work remains preclinical and untested in humans.