Aluminum-based adjuvants (aluminum salts or alum) are widely used in human vaccination, although their mechanisms of　action are poorly understood. The authors report that, in mice, alum causes cell death and the subsequent release of host cell DNA, which acts as a potent endogenous immunostimulatory signal mediating alum adjuvant activity. Furthermore, they propose that host DNA signaling differentially regulates IgE and IgG1 production after alum-adjuvanted immunization. The authors suggest that, on the one hand, host DNA induces primary B cell responses, including IgG1 production, through interferon response factor 3 (Irf3)-independent mechanisms. On the other hand, they suggest that host DNA also stimulates 'canonical' T helper type 2 (TH2) responses, associated with IgE isotype switching and peripheral effector responses, through Irf3-dependent mechanisms. The finding that host cell DNA released from dying cells acts as a damage-associated molecular pattern that mediates alum adjuvant activity may increase their understanding of the mechanisms of action of current vaccines and help in the design of new adjuvants.

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Contact:

Ken J. Ishii
Vaccine Science
Immunology Frontier Research Center (IFReC), Osaka University