Differences in the innate immune response between aluminum-based vaccine adjuvants 4319

Abstract Description Aluminum hydroxide (AH) and aluminum phosphate (AP) are widely used vaccine adjuvants, yet their mechanisms of action remain poorly understood. The choice of these adjuvants is mainly guided by their physical and chemical properties, while little is known about potential functional differences. Here, we demonstrate that AP induced significantly higher IL-1β secretion than AH in human THP-1 macrophages and mouse bone marrow-derived macrophages (BMDMs) under LPS-primed conditions. Inhibition by MCC950 and the use of macrophages from NLRP3-deficient mice confirmed that IL-1β secretion induced by both adjuvants in vitro was dependent on the NLRP3 inflammasome. In vivo, AH and AP also showed different kinetics of innate immune cell recruitment, with AP inducing a higher number of neutrophils and dendritic cells at 96 hours after injection. These findings highlight biological differences between AH and AP, with distinct inflammatory profiles and kinetics of immune cell recruitment. In addition, the role of the NLRP3 inflammasome was examined in vivo to understand its role in driving immunostimulation by AH and AP. Both adjuvants elicited similar IgG and IgG1 responses in wild-type and NLRP3-deficient mice indicating that NLRP3 is not as critical to the immune response induced by aluminum-adjuvanted vaccines. Topic Categories Vaccines and Immunotherapy (VAC)