Al-fumarate, a Metal-Organic Framework encapsulating antigen as a potent, versatile and resorbable vaccine adjuvant

Abstract

Although used for one century in billions of people as the vaccine adjuvant with the best benefit/side-effect balance, aluminium salts/gels have drawbacks of rapid leakage of antigens from the injection site and indefinite persistence. Herein, we propose an alternative to canonical Al-adjuvant. Proteins, nucleic acids, and bacteria were successfully encapsulated within an Al-based Metal-Organic Framework (MOF), namely Al-fumarate, using a synthesis process in water and room temperature, compatible with bio-entities preservation. Mice immunizations demonstrated antigenicity preservation of tetanus toxoid and inactivated E. coli, and a stronger adjuvant effect of Al-fumarate than benchmark Al-adjuvant (Alhydrogel) with an initial slow antigen release and a protective effect. The Al-fumarate vaccine formulation was fully resorbable in vivo, disappearing from the injection site, was not exhibiting any toxicity, and was stable for two years. The limitation of Al adjuvants as eliciting only antibody responses was also overcome by co-immobilisation of CpG 1018 with tetanus toxoid.