Enteric Diseases Department, Naval Medical Research Center, Silver Spring, MD, United States.
Bloomberg School of Public Health, Johns Hopkins University, Baltimore, MD, United States.
Vaccine. 2017 Dec 14;35(49 Pt A):6813-6818. doi: 10.1016/j.vaccine.2017.05.068. Epub 2017 Jun 3.
The controlled human infection model (CHIM) to assess the efficacy of vaccines against Shigella and enterotoxigenic Escherichia coli (ETEC) has several unique features that could significantly enhance the ability to test candidate vaccines. Despite increasing interest in these models, questions remain as to how to best incorporate them into vaccine development and how to maximize results. We designed a workshop focused on CHIM as part of the Vaccines Against Shigella and ETEC (VASE) Conference. The workshop, using the World Café method, focused on; clinical outcomes, nonclinical outcomes and model standardization. Researchers with a variety of expertise and experience rotated through each focus area and discussed relevant sub-topics. The results of these discussions were presented and questions posed to guide future workshops. Clinical endpoint discussions focused on the need for harmonized definitions; optimized attack rates; difficulties of sample collection and a need for non-stool based endpoints. Nonclinical discussions centered on evolving omics-based opportunities, host predictors of susceptibility and novel characterizations of the immune response. Model standardization focused on the value of shared procedures across institutions for clinical and non-clinical endpoints as well as for strain preparation and administration and subject selection. Participants agreed CHIMs for Shigella and ETEC vaccine development could accelerate vaccine development of a promising candidate; however, it was also appreciated that variability in the model and our limited understand of the host-pathogen interaction may yield results that could negatively impact a suitable candidate. Future workshops on CHIM are needed to ensure the optimal application of these models moving forward.
人类感染控制模型（CHIM）可用于评估针对志贺氏菌和肠产毒性大肠杆菌（ETEC）的疫苗的疗效，它具有几个独特的特点，可以显著提高候选疫苗的测试能力。尽管人们对这些模型的兴趣日益增加，但仍存在一些问题，例如如何将它们最好地纳入疫苗开发中，以及如何最大限度地提高结果。我们设计了一个以 CHIM 为重点的研讨会，作为志贺氏菌和 ETEC 疫苗（VASE）会议的一部分。该研讨会采用世界咖啡馆的方法，重点关注临床结果、非临床结果和模型标准化。具有各种专业知识和经验的研究人员轮流进入每个重点领域，并讨论相关的子主题。这些讨论的结果被提出，并提出问题以指导未来的研讨会。临床终点讨论集中在需要统一定义；优化攻击率；样本收集的困难和需要非粪便终点。非临床讨论集中在基于组学的机会的演变、宿主易感性预测因子以及免疫反应的新特征。模型标准化集中在机构之间为临床和非临床终点以及菌株制备和给药以及受试者选择共享程序的价值。与会者一致认为，CHIM 可用于志贺氏菌和 ETEC 疫苗开发，可以加速有前途候选疫苗的开发；然而，人们也认识到，模型的可变性和我们对宿主-病原体相互作用的有限理解可能会产生可能对合适候选物产生负面影响的结果。需要进行 CHIM 未来研讨会，以确保这些模型的最佳应用。
