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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.

DOI:10.1080/14760584.2024.2382725
PMID:39042099
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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Adjuvant system AS01: from mode of action to effective vaccines.佐剂系统 AS01:从作用模式到有效疫苗。
Expert Rev Vaccines. 2024 Jan-Dec;23(1):715-729. doi: 10.1080/14760584.2024.2382725. Epub 2024 Aug 5.
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Adjuvant system AS01: helping to overcome the challenges of modern vaccines.佐剂系统AS01:助力克服现代疫苗的挑战。
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Toll-like receptor 4 signaling in hematopoietic-lineage cells contributes to the enhanced activity of the human vaccine adjuvant AS01.TLR4 信号在造血细胞中的作用有助于增强人用疫苗佐剂 AS01 的活性。
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Vaccine adjuvant systems containing monophosphoryl lipid A and QS21 induce strong and persistent humoral and T cell responses against hepatitis B surface antigen in healthy adult volunteers.含有单磷酰脂质A和QS21的疫苗佐剂系统在健康成年志愿者中诱导出针对乙肝表面抗原的强烈且持久的体液和T细胞应答。
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An innate immune signature induced by AS01- or AS03-adjuvanted vaccines predicts the antibody response magnitude and quality consistently over time.AS01 或 AS03 佐剂疫苗诱导的固有免疫特征可随时间一致地预测抗体反应幅度和质量。
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