VACCINE

Journal Of Experimental Medicine • April 2008
Alum adjuvant
boosts adaptive immunity
by inducing uric acid and activating
inflammatory dendritic cells
Kool M1, Soullié T, van Nimwegen M,
Willart MA, Muskens F, Jung S, Hoogsteden HC,
Hammad H, Lambrecht BN.
Department of Pulmonary Medicine
Erasmus University Medical Centre
3015 GD Rotterdam, Netherlands
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.
“Alum (aluminum hydroxide)
is the most widely used adjuvant
in human vaccines, but the mechanism
of its adjuvanticity remains unknown.”
http://www.ncbi.nlm.nih.gov/pubmed/?term=18362170