Controlled Human Infection Models To Accelerate Vaccine Development.

IF 19 1区 医学 Q1 MICROBIOLOGY Clinical Microbiology Reviews Pub Date : 2022-09-21 Epub Date: 2022-07-06 DOI:10.1128/cmr.00008-21
Robert K M Choy, A Louis Bourgeois, Christian F Ockenhouse, Richard I Walker, Rebecca L Sheets, Jorge Flores
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引用次数: 7

Abstract

The timelines for developing vaccines against infectious diseases are lengthy, and often vaccines that reach the stage of large phase 3 field trials fail to provide the desired level of protective efficacy. The application of controlled human challenge models of infection and disease at the appropriate stages of development could accelerate development of candidate vaccines and, in fact, has done so successfully in some limited cases. Human challenge models could potentially be used to gather critical information on pathogenesis, inform strain selection for vaccines, explore cross-protective immunity, identify immune correlates of protection and mechanisms of protection induced by infection or evoked by candidate vaccines, guide decisions on appropriate trial endpoints, and evaluate vaccine efficacy. We prepared this report to motivate fellow scientists to exploit the potential capacity of controlled human challenge experiments to advance vaccine development. In this review, we considered available challenge models for 17 infectious diseases in the context of the public health importance of each disease, the diversity and pathogenesis of the causative organisms, the vaccine candidates under development, and each model's capacity to evaluate them and identify correlates of protective immunity. Our broad assessment indicated that human challenge models have not yet reached their full potential to support the development of vaccines against infectious diseases. On the basis of our review, however, we believe that describing an ideal challenge model is possible, as is further developing existing and future challenge models.

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控制人类感染模型加速疫苗开发。
开发针对传染病的疫苗的时间很长,而且进入大规模第三阶段实地试验阶段的疫苗往往无法提供所需的保护效力。在适当的开发阶段应用感染和疾病的受控人类挑战模型可以加速候选疫苗的开发,事实上,在一些有限的情况下已经成功地做到了这一点。人类挑战模型可能用于收集有关发病机制的关键信息,为疫苗的菌株选择提供信息,探索交叉保护性免疫,识别感染诱导或候选疫苗引发的保护的免疫相关性和保护机制,指导适当试验终点的决定,并评估疫苗的疗效。我们编写这份报告是为了激励其他科学家利用受控人体挑战实验的潜在能力来推进疫苗开发。在这篇综述中,我们从每种疾病的公共卫生重要性、致病生物体的多样性和发病机制、正在开发的候选疫苗以及每种模型评估它们和确定保护性免疫相关性的能力的角度,考虑了17种传染病的可用挑战模型。我们的广泛评估表明,人类挑战模型尚未充分发挥潜力,支持开发针对传染病的疫苗。然而,根据我们的审查,我们认为描述一个理想的挑战模型是可能的,进一步发展现有和未来的挑战模型也是可能的。
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来源期刊
Clinical Microbiology Reviews
Clinical Microbiology Reviews 医学-微生物学
CiteScore
54.20
自引率
0.50%
发文量
38
期刊介绍: Clinical Microbiology Reviews (CMR) is a journal that primarily focuses on clinical microbiology and immunology.It aims to provide readers with up-to-date information on the latest developments in these fields.CMR also presents the current state of knowledge in clinical microbiology and immunology.Additionally, the journal offers balanced and thought-provoking perspectives on controversial issues in these areas.
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