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佐剂系统 AS01:从作用模式到有效疫苗。

Adjuvant system AS01: from mode of action to effective vaccines.

机构信息

GSK, Wavre, Belgium.

GSK, Rixensart, Belgium.

出版信息

Expert Rev Vaccines. 2024 Jan-Dec;23(1):715-729. doi: 10.1080/14760584.2024.2382725. Epub 2024 Aug 5.

Abstract

INTRODUCTION

The use of novel adjuvants in human vaccines continues to expand as their contribution to preventing disease in challenging populations and caused by complex pathogens is increasingly understood. AS01 is a family of liposome-based vaccine Adjuvant Systems containing two immunostimulants: 3--desacyl-4'-monophosphoryl lipid A and the saponin QS-21. AS01-containing vaccines have been approved and administered to millions of individuals worldwide.

AREAS COVERED

Here, we report advances in our understanding of the mode of action of AS01 that contributed to the development of efficacious vaccines preventing disease due to malaria, herpes zoster, and respiratory syncytial virus. AS01 induces early innate immune activation that induces T cell-mediated and antibody-mediated responses with optimized functional characteristics and induction of immune memory. AS01-containing vaccines appear relatively impervious to baseline immune status translating into high efficacy across populations. Currently licensed AS01-containing vaccines have shown acceptable safety profiles in clinical trials and post-marketing settings.

EXPERT OPINION

Initial expectations that adjuvantation with AS01 could support effective vaccine responses and contribute to disease control have been realized. Investigation of the utility of AS01 in vaccines to prevent other challenging diseases, such as tuberculosis, is ongoing, together with efforts to fully define its mechanisms of action in different vaccine settings.

摘要

简介

随着人们越来越了解新型佐剂在预防复杂病原体引起的挑战性人群疾病方面的作用,其在人类疫苗中的应用不断扩大。AS01 是一系列基于脂质体的疫苗佐剂系统,包含两种免疫增强剂:3-O-去酰基-4'-单磷酰脂质 A 和皂苷 QS-21。含有 AS01 的疫苗已在全球范围内获得批准并用于数百万个人。

涵盖领域

本文报告了我们对 AS01 作用机制的理解的进展,这些进展有助于开发针对疟疾、带状疱疹和呼吸道合胞病毒等疾病的有效疫苗。AS01 诱导早期先天免疫激活,诱导具有优化功能特征的 T 细胞介导和抗体介导的反应,并诱导免疫记忆。含有 AS01 的疫苗似乎相对不受基线免疫状态的影响,在不同人群中均具有较高的疗效。目前获得许可的含有 AS01 的疫苗在临床试验和上市后环境中表现出可接受的安全性。

专家意见

最初预期佐剂 AS01 可以支持有效的疫苗反应并有助于疾病控制,这一预期已经实现。目前正在研究 AS01 在预防其他挑战性疾病(如结核病)疫苗中的效用,同时还努力在不同疫苗环境中充分确定其作用机制。

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