Alum adjuvant boosts adaptive immunity by inducing uric acid and activating inflammatory dendritic cells

TLDR

Alum is the most widely used vaccine adjuvant, yet its mechanism of action remains unknown. Alum enhances immunity by inducing uric acid, which activates inflammatory dendritic cells that present antigen and drive a persistent Th2 response; this effect is lost when CD11c⁺ cells are depleted, in MyD88‑deficient mice, or after uricase treatment.

Abstract

Alum (aluminum hydroxide) is the most widely used adjuvant in human vaccines, but the mechanism of its adjuvanticity remains unknown. In vitro studies showed no stimulatory effects on dendritic cells (DCs). In the absence of adjuvant, Ag was taken up by lymph node (LN)–resident DCs that acquired soluble Ag via afferent lymphatics, whereas after injection of alum, Ag was taken up, processed, and presented by inflammatory monocytes that migrated from the peritoneum, thus becoming inflammatory DCs that induced a persistent Th2 response. The enhancing effects of alum on both cellular and humoral immunity were completely abolished when CD11c+ monocytes and DCs were conditionally depleted during immunization. Mechanistically, DC-driven responses were abolished in MyD88-deficient mice and after uricase treatment, implying the induction of uric acid. These findings suggest that alum adjuvant is immunogenic by exploiting “nature's adjuvant,” the inflammatory DC through induction of the endogenous danger signal uric acid.