ISCOMATRIX® adjuvant is a saponin-based particulate vaccine adjuvant with a superior ability to induce immune responses in humans and mice. By facilitating early innate immune activation, ISCOMATRIX® adjuvant contributes to the induction of cross-presentation by dendritic cells, subsequently promoting antigen-specific CD8+ and CD4+ T cell activation, as well as robust and prolonged antibody responses in various animal models of vaccination and several clinical studies in patients. However, although we have recently demonstrated that potent inflammasome activation is one of the initial underlying mechanisms of ISCOMATRIX® adjuvant activity, early involvement of other inflammatory pathways and key immune cell subsets in the profound effectiveness of the adjuvant remains largely elusive.
We have thus examined transcriptional changes in multiple cell subsets within the draining lymph nodes of mice, following ISCOMATRIX® adjuvant vaccination. Careful analysis revealed the induction of a common inflammatory gene signature across dendritic cell subsets, monocytes and neutrophils within hours of ISCOMATRIX® adjuvant treatment. Moreover, the adjuvant induced a plethora of key cytokines, chemokines and costimulatory molecules, as well as pathways involved in antigen presentation and cellular migration in each of the immune cell subsets investigated. Additionally, we were able to demonstrate the crucial involvement of interferon-alpha signaling in the ISCOMATRIX® adjuvant–induced immune activation and we are investigating the roles of macrophages and neutrophils in mediating subsequent cellular and humoral immune responses. Taken together, our results reveal key features of the mechanism of action of ISCOMATRIX® adjuvant and highlight its potential role as an adjuvant in various clinical vaccination settings.