IL-1 delineates squalene-based adjuvant efficacy and reactogenicity in a cell-type specific manner

Among these, A-910823 and AS03 are recognized squalene-based adjuvants containing α-tocopherol. Although α-tocopherol-containing squalene-based adjuvants are known to enhance humoral immune responses and inflammatory cytokine production, their underlying mechanisms remain unclear.

Here, we found that A-910823 regulated IL-1 signaling pathway gene expression and IL-1α and IL-1β protein expressions in an α-tocopherol-dependent manner. While the source of IL-1α was mainly from eosinophils, IL-1β was from wide range of myeloid cells. Mechanistically, IL-1β/CD11c+ cell-IL-1R1/MyD88 axis mediated adjuvant efficacy, however, systemic reactogenicity was induced by the IL-1β/IL-1R1/MyD88/IL-6/cyclooxygenase 2 axis which was unexpectedly distinct mechanism from the local reactogenicity that was mediated by the eosinophil-derived IL-1α/IL-1R1/MyD88 axis.