Center for Vaccine Innovation and Access, PATH, 455 Massachusetts Avenue NW, Suite 1000, Washington, DC 20001, USA.
Bill & Melinda Gates Foundation, PO Box 23350, Seattle, WA 98102, USA.
Vaccine. 2019 Aug 14;37(35):4823-4829. doi: 10.1016/j.vaccine.2019.06.080.
In response to global interest in the development of a universal influenza vaccine, the Bill & Melinda Gates Foundation, PATH, and the Global Funders Consortium for Universal Influenza Vaccine Development convened a meeting of experts (London, UK, May 2018) to assess the role of a standardized controlled human influenza virus infection model (CHIVIM) towards the development of novel influenza vaccine candidates. This report (in two parts) summarizes those discussions and offers consensus recommendations. This article (Part 1) covers challenge virus selection, regulatory and ethical considerations, and issues concerning standardization, access, and capacity. Part 2 covers specific methodologic considerations. Current methods for influenza vaccine development and licensure require large costly field trials. The CHIVIM requires fewer subjects and the controlled setting allows for better understanding of influenza transmission and host immunogenicity. The CHIVIM can be used to identify immune predictors of disease for at-risk populations and to measure efficacy of potential vaccines for further development. Limitations to the CHIVIM include lack of standardization, limited access to challenge viruses and assays, lack of consensus regarding role of the CHIVIM in vaccine development pathway, and concerns regarding risk to study participants and community. To address these issues, the panel of experts recommended that WHO and other key stakeholders provide guidance on standardization, challenge virus selection, and risk management. A common repository of well-characterized challenge viruses, harmonized protocols, and standardized assays should be made available to researchers. A network of research institutions performing CHIVIM trials should be created, and more study sites are needed to increase capacity. Experts agreed that a research network of institutions working with a standardized CHIVIM could contribute important data to support more rapid development and licensure of novel vaccines capable of providing long-lasting protection against seasonal and pandemic influenza strains.
针对全球对通用流感疫苗开发的兴趣，比尔及梅琳达·盖茨基金会、PATH 和全球流感疫苗开发者联盟召集了一次专家会议（2018 年 5 月，英国伦敦），以评估标准化的人体受控流感病毒感染模型（CHIVIM）在开发新型流感疫苗候选物方面的作用。本报告（分两部分）总结了这些讨论并提出了共识建议。本文（第 1 部分）涵盖了挑战病毒选择、监管和伦理问题，以及标准化、获取和能力方面的问题。第 2 部分涵盖了具体的方法学考虑因素。目前流感疫苗开发和许可的方法需要进行大规模昂贵的现场试验。CHIVIM 需要较少的受试者，且受控环境允许更好地了解流感传播和宿主免疫原性。CHIVIM 可用于确定高危人群疾病的免疫预测指标，并衡量潜在疫苗的疗效，以进一步开发。CHIVIM 的局限性包括缺乏标准化、对挑战病毒和检测方法的有限获取、对 CHIVIM 在疫苗开发途径中的作用缺乏共识以及对研究参与者和社区风险的担忧。为了解决这些问题，专家组建议世卫组织和其他利益攸关方就标准化、挑战病毒选择和风险管理提供指导。应向研究人员提供经过良好特征描述的挑战病毒、协调一致的方案和标准化检测方法的通用存储库。应创建一个使用 CHIVIM 进行试验的研究机构网络，并需要更多的研究地点来提高能力。专家们一致认为，一个与标准化 CHIVIM 合作的研究机构网络可以提供重要数据，以支持更快速地开发和许可有能力提供针对季节性和大流行性流感株的长效保护的新型疫苗。
