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在候选带状疱疹糖蛋白E亚单位疫苗中,AS01与其他佐剂系统的临床前比较评估

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

作者信息

Fochesato Michel, Dendouga Najoua, Boxus Mathieu

机构信息

a GSK Vaccines; Rue de l'Institut ; 89; 1330 ; Rixensart ; Belgium.

出版信息

Hum Vaccin Immunother. 2016 Aug 2;12(8):2092-2095. doi: 10.1080/21645515.2016.1154247. Epub 2016 Mar 2.

DOI:10.1080/21645515.2016.1154247
PMID:26933767
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC4994747/
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 (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.

摘要

候选疫苗HZ/su正在研发中,用于预防带状疱疹疾病(HZ)。HZ的发生归因于水痘带状疱疹病毒(VZV)特异性T细胞免疫力的下降。HZ/su含有VZV抗原gE和佐剂系统AS01(MPL和QS-21的脂质体配方)。在临床试验中,AS01可增强CD4 T细胞对gE的反应。在其他疫苗的临床试验中,佐剂系统AS03和AS04也可增强抗原特异性CD4 T细胞反应。因此,本研究的目的是在经减毒活VZV免疫的C57BL6小鼠中评估与AS01、AS01(MPL和QS-21比AS01少50%)、AS03或AS04配制的gE。接种疫苗四周后,对gE/AS01的gE特异性CD4 T细胞反应分别比对gE/AS03、gE/AS04和gE/AS01的反应高5.4倍、2.8倍和2.2倍(p<0.001)。因此,在VZV免疫的小鼠模型中,AS01对gE的CD4 T细胞反应增强最为明显,这进一步支持了AS01在HZ/su配方中的应用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/817d/4994747/de1093c852f7/khvi-12-08-1154247-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/817d/4994747/89461e63b37b/khvi-12-08-1154247-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/817d/4994747/de1093c852f7/khvi-12-08-1154247-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/817d/4994747/89461e63b37b/khvi-12-08-1154247-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/817d/4994747/de1093c852f7/khvi-12-08-1154247-g002.jpg

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