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Adjuvants such as the aluminum compounds (alum) have been dominantly used in many vaccines due to their immunopotentiation and safety records since 1920s. However, how these mineral agents influence the immune response to vaccination remains elusive. Many hypotheses exist as to the mode of action of these adjuvants, such as depot formation, antigen (Ag) targeting, and the induction of inflammation. These hypotheses are based on many  in vitro  and few  in vivo  studies. Understanding how cells interact with adjuvants  in vivo  will be crucial to fully understanding the mechanisms of action of these adjuvants. Interestingly, how alum influences the target cell at both the cellular and molecular level, and the consequent innate and adaptive responses, will be critical in the rational design of effective vaccines against many diseases. Thus, in this review, mechanisms of action of alum have been discussed based on available  in vitro  vs  in vivo  evidences to date.

The mechanisms of action of vaccines containing aluminum adjuvants: an in vitro vs in vivo paradigm