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You are here: Home / RESEARCH . . . . / Vaccine Adjuvants / Aluminum Adjuvants / DNA released from dying host cells mediates aluminum adjuvant activity

DNA released from dying host cells mediates aluminum adjuvant activity

July 31, 2011 By Jonathan Leave a Comment

 

Nature Medicine
(2011)doi:10.1038/nm.2403

Received: 11 February 2011
Accepted: 19 May 2011
Published online: 17 July 2011

Abstract

Aluminum-based adjuvants (aluminum salts or alum) are widely used in human vaccination, although their mechanisms of action are poorly understood. Here we 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, we propose that host DNA signaling differentially regulates IgE and IgG1 production after alum-adjuvanted immunization. We 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, we 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 DNA released from dying cells acts as a damage-associated molecular pattern that mediates alum adjuvant activity may increase our understanding of the mechanisms of action of current vaccines and help in the design of new adjuvants.

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Filed Under: Aluminum Adjuvants, Vaccine Science Tagged With: aluminum adjuvant, host DNA, immunizations, vaccinations, vaccine science

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