The Adjuvant System AS01 upregulates neutrophil CD14 expression and neutrophil-associated antigen transport in the local lymphatic network

Summary

The liposome-based Adjuvant System AS01 is under evaluation for use in several vaccines in clinical development. We have previously shown that AS01 injected with hepatitis B surface antigen (HBsAg) induces a distinct cellular signature within the draining lymphatics that enhances local lymphocyte recruitment and antigen-specific humoral immunity. Here, we show that AS01-induced neutrophil recruitment is associated with increased expression of CD14 and enhanced antigen uptake capacity in neutrophils from both afferent and efferent lymphatic compartments in the first 48h after vaccination. Significant and transient increases in CD14 expression on systemic neutrophils were also observed following primary and boost vaccination with HBsAg-AS01, however were not observed following additional encounter with HBsAg-alone or HBsAg-alum. These results show that following immunisation with AS01, neutrophils expressing higher levels of CD14 are both more abundant and efficient at antigen uptake, warranting further investigation into the role of neutrophil associated CD14 in the adjuvanticity of AS01. This article is protected by copyright. All rights reserved.