Mechanism of action of licensed vaccine adjuvants.
Despite the fact that alum and oil-in-water emulsions have been used for decades as human vaccine adjuvants in a large number of individuals, their mechanism of action is not completely understood. It has been reported that these particulate adjuvants act by increasing antigen availability and uptake by immune cells. However, recent work on alum and on the squalene-based emulsion MF59, has demonstrated that besides antigen delivery functions, these classes of adjuvants can also activate innate immunity pathways in vivo, generating an immunocompetent environment at injection site. Interestingly, it has been demonstrated that alum adjuvanticity depends on the activation of a protein complex called NLPR3/inflammasome, which is required for the correct processing of a number of pro-inflammatory cytokines, including IL1beta. More work needs to be performed to investigate if the inflammasome is also required for the activity of MF59 and of other particulate vaccine adjuvants.
Tritto
Elaine
E
Novartis Vaccines and Diagnostics, Via Fiorentina, 1 - 53100 Siena, Italy.
Mosca
Flaviana
F
De Gregorio
Ennio
E
D000276:Adjuvants, Immunologic / Q000494:pharmacology*; D000534:Alum Compounds / Q000494:pharmacology*; D000818:Animals; D002352:Carrier Proteins / Q000502:physiology; D003713:Dendritic Cells / Q000502:physiology; D006801:Humans; D007113:Immunity, Innate / Q000187:drug effects; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein; D011136:Polysorbates / Q000494:pharmacology*; D013185:Squalene / Q000494:pharmacology*; D051193:Toll-Like Receptors / Q000502:physiology
D000276:Adjuvants, Immunologic; D000534:Alum Compounds; D002352:Carrier Proteins; C089950:MF59 oil emulsion; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein; C453881:NLRP3 protein, human; D011136:Polysorbates; D051193:Toll-Like Receptors; C041524:aluminum sulfate; D013185:Squalene