title: 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 AS01B(liposome-based formulation of MPL and QS-21). In clinical trials, AS01Benhances 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 AS01B, AS01E(50% less MPL and QS-21 than AS01B), AS03 or AS04 in C57BL6 mice primed with live-attenuated VZV. Four-weeks post-vaccination, the gE-specific CD4+T-cell response to gE/AS01Bwas 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 AS01B, and adds further support for the use of AS01Bin the HZ/su formulation.
authors.affiliation: a GSK Vaccines; Rue de l'Institut ; 89; 1330 ; Rixensart ; Belgium.
authors.forename: Michel
authors.initials: M
authors.lastname: Fochesato
authors.affiliation: a GSK Vaccines; Rue de l'Institut ; 89; 1330 ; Rixensart ; Belgium.
authors.forename: Najoua
authors.initials: N
authors.lastname: Dendouga
authors.affiliation: a GSK Vaccines; Rue de l'Institut ; 89; 1330 ; Rixensart ; Belgium.
authors.forename: Mathieu
authors.initials: M
authors.lastname: Boxus
mesh_terms: D000276:Adjuvants, Immunologic / Q000008:administration & dosage*; D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D004338:Drug Combinations; D004353:Drug Evaluation, Preclinical; D053061:Herpes Zoster Vaccine / Q000008:administration & dosage* / Q000276:immunology*; D008050:Lipid A / Q000008:administration & dosage / Q000031:analogs & derivatives*; D008810:Mice, Inbred C57BL; D012503:Saponins / Q000008:administration & dosage*; D022223:Vaccines, Subunit / Q000008:administration & dosage / Q000276:immunology; D014759:Viral Envelope Proteins / Q000008:administration & dosage / Q000276:immunology
chemical_list: C501939:ASO2A adjuvant; D000276:Adjuvants, Immunologic; D004338:Drug Combinations; D053061:Herpes Zoster Vaccine; D008050:Lipid A; D012503:Saponins; D022223:Vaccines, Subunit; D014759:Viral Envelope Proteins; C056913:glycoprotein E, varicella-zoster virus
keywords: MPL; QS-21; Varicella-zoster virus; herpes zoster Adjuvant System; vaccine