Journal ArticleDOI
DNA released from dying host cells mediates aluminum adjuvant activity
Thomas Marichal,Keiichi Ohata,Denis Bedoret,Claire Mesnil,Catherine Sabatel,Kouji Kobiyama,Pierre Lekeux,Cevayir Coban,Shizuo Akira,Ken Ishii,Fabrice Bureau,Christophe Desmet +11 more
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TLDR
The finding that host DNA released from dying cells acts as a damage-associated molecular pattern that mediates alum adjuvant activity may increase the understanding of the mechanisms of action of current vaccines and help in the design of new adjuvants.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 (T H 2) 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.read more
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Multi-faceted regulation of IgE production and humoral memory formation.
Kei Haniuda,Daisuke Kitamura +1 more
TL;DR: Recent advances in understanding of the mechanisms that control the production of IgE and formation of Ig E-type humoral memory are summarized, focusing on the B cell immune responses.
Journal ArticleDOI
Pharmacodynamic and safety considerations for influenza vaccine and adjuvant design.
TL;DR: This review aims to explain the recently developed genomics analysis-based vaccine adjuvant safety evaluation tools verified by AddaVaxTM and polyinosinic-polycytidylic acid (poly I:C) using 18 biomarker genes and whole-virion inactivated influenza vaccine as a toxicity control.
Journal ArticleDOI
Clinical phase II and III studies of an AS03-adjuvanted H5N1 influenza vaccine produced in an EB66® cell culture platform.
Masafumi Endo,Mitsuyoshi Tanishima,Kayo Ibaragi,Kenshi Hayashida,Tadashi Fukuda,Tetsuro Tanabe,Takeshi Naruse,Yoichiro Kino,Kohji Ueda +8 more
TL;DR: An AS03‐adjuvanted H5N1 influenza vaccine produced in an EB66® cell culture platform (KD‐295) is developed and presented at the European Vaccine Conference in Strasbourg.
References
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Osamu Takeuchi,Shizuo Akira +1 more
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Sanjeev Mariathasan,David S. Weiss,Kim Newton,Jacqueline McBride,Karen O'Rourke,Meron Roose-Girma,Wyne P. Lee,Yvette Weinrauch,Denise M. Monack,Vishva M. Dixit +9 more
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Journal ArticleDOI
Silica crystals and aluminum salts activate the NALP3 inflammasome through phagosomal destabilization
Veit Hornung,Franz Bauernfeind,Annett Halle,Eivind O. Samstad,Eivind O. Samstad,Hajime Kono,Kenneth L. Rock,Katherine A. Fitzgerald,Eicke Latz,Eicke Latz +9 more
TL;DR: It is demonstrated that silica and aluminum salt crystals activated inflammasomes formed by the cytoplasmic receptor NALP3, which senses lysosomal damage as an endogenous 'danger' signal.
Journal ArticleDOI
Sterile inflammation: sensing and reacting to damage
Grace Y. Chen,Gabriel Núñez +1 more
TL;DR: The triggers and receptor pathways that result in sterile inflammation and its impact on human health are reviewed.