Nano-formulated bisphosphonate adjuvants simultaneously induce humoral and cellular immunity

ABSTRACT: Adjuvant is an important component of vaccines However, given the limitation of existing adjuvants in variety and mechanism, developing a unique and effective adjuvant is urgently needed for clinal applications. Recent studies have implicated that the mevalonate pathway plays an essential role in vaccine adjuvant discovery[1]. It indicates that bisphosphonate, an inhibitor of mevalonate metabolism pathway, may have a potential adjuvant effect. However, the free forms of bisphosphonate are prone to be eliminated quickly by the circulatory system and rapidly bind to bone tissue in vivo. Herein, we developed one kind of nano-formulated bisphosphonate adjuvants (NBAs) based on the coordination reaction of zoledronic acid and calcium. NBAs significantly enhanced the delivery and distribution of zoledronic acid to lymph nodes and stimulated the innate immunity of antigen-presenting cells. In vivo experiments demonstrated that NBAs elicited outstanding humoral and cellular immunity. Furthermore, we propose a new mechanism for their adjuvant effects. NBAs disrupt the electron transport chain by reducing coenzyme Q synthesis, promote the production of mitochondrial reactive oxygen species (mtROS) and activate the mitochondrial antiviral protein (MAVS), thereby enhancing downstream inflammatory signaling pathways and exerting their adjuvant effect. In summary, NBAs significantly improve the immune response via the adjuvant effect based on mevalonate metabolism, which paves the road for its potential adjuvant development.

INSTRUMENT(S): Liquid Chromatography MS - negative - reverse phase

PROVIDER: MTBLS11696 | MetaboLights | 2026-03-03

REPOSITORIES: MetaboLights