Comparative preclinical evaluation of AS01 versus other Adjuvant Systems in a candidate herpes zoster glycoprotein E subunit vaccine.

The candidate vaccine HZ/su is being developed to prevent herpes-zoster disease (HZ). HZ occurrence is attributed to declines in varicella-zoster virus (VZV) specific T-cell immunity. HZ/su contains VZV antigen, gE, and Adjuvant System AS01 (liposome-based formulation of MPL and QS-21). In clinical trials, AS01 enhances CD4 T-cell responses to gE. In clinical trials of other vaccines, Adjuvant Systems AS03 and AS04 also enhance antigen-specific CD4 T-cell responses. Hence the purpose of this study was to evaluate gE formulated with AS01, AS01 (50% less MPL and QS-21 than AS01), AS03 or AS04 in C57BL6 mice primed with live-attenuated VZV. Four-weeks post-vaccination, the gE-specific CD4 T-cell response to gE/AS01 was 5.4, 2.8 and 2.2-fold greater than those to gE/AS03, gE/AS04 and gE/AS03, respectively (p<0.001). Therefore in the VZV-primed mouse model, CD4 T-cell responses to gE appeared most enhanced by AS01, and adds further support for the use of AS01 in the HZ/su formulation.