Alum, the most common adjuvant in non-living vaccines, has a record of successful use in human vaccination where it promotes antibody-mediated protective immunity. However, alum is a poor inducer of cellular immune responses. The mechanism underlying the selective enhancement of humoral immunity is still not well understood. Here, to provide an insight into its mode of action, recent findings regarding innate immune responses induced by alum and their impact on adaptive immunity are described, with a particular emphasis on early recognition of alum, including NLRP3 and PI3 kinase activation, adjuvant-induced cell death and the release of endogenous danger signals. Expanding our knowledge of alum-induced immunomodulation will greatly enhance our capacity to rationally develop novel adjuvants with specific properties.
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