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

ABSTRACT

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_B (liposome-based formulation of MPL and QS-21). In clinical trials, AS01_B 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_B, AS01_E (50% less MPL and QS-21 than AS01_B), 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_B 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_B, and adds further support for the use of AS01_B in the HZ/su formulation.

KEYWORDS:

• herpes zoster Adjuvant System
• MPL
• QS-21
• Varicella-zoster virus
• vaccine

Abbreviations

CI	=	confidence interval
gE	=	glycoprotein E
HZ	=	herpes zoster
GMC	=	geometric mean concentration
GMF	=	geometric mean frequency
MPL	=	3-O-desacyl-4'-monophosphoryl lipid A
QS-21	=	Quillaja saponaria Molina, fraction 21
VZV	=	varicella zoster virus

Disclosure of potential conflicts of interest

All authors were involved in the conception and design of the studies. ND, MB, MF acquired the data. All authors analyzed and interpreted the results. All authors were involved in drafting the manuscript or revising it critically for important intellectual content. All authors had full access to the data and approved the manuscript before it was submitted by the corresponding author.

All authors have declared the following interests: all authors are employees of the GSK group of companies. MB and ND own GSK stocks.

Acknowlegements

Animal husbandry and experiments were ethically reviewed and carried out in accordance with European Directive 2010/63/EU and GlaxoSmithKline Biologicals SA policy. We thank Sandra Giannini for scientific advice and Frédéric Renaud for performing the statistical analyses (both GSK Vaccines, Belgium). Matthew Morgan (MG Science Communications, Belgium) provided scientific writing services, and Ulrike Krause (GSK Vaccines, Belgium) provided editorial advice and coordinated the manuscript's development.

Funding

This work was sponsored by GlaxoSmithKline Biologicals SA who also took responsibility for all costs associated with the development and publishing of the manuscript, including scientific writing assistance.