Barton Amber J, Hill Jennifer, Pollard Andrew J, Blohmke Christoph J
Oxford Vaccine Group, Department of Paediatrics, University of Oxford and the NIHR Oxford Biomedical Research Centre, Oxford, United Kingdom.
Front Immunol. 2017 Dec 18;8:1839. doi: 10.3389/fimmu.2017.01839. eCollection 2017.
Human challenge models, in which volunteers are experimentally infected with a pathogen of interest, provide the opportunity to directly identify both natural and vaccine-induced correlates of protection. In this review, we highlight how the application of transcriptomics to human challenge studies allows for the identification of novel correlates and gives insight into the immunological pathways required to develop functional immunity. In malaria challenge trials for example, innate immune pathways appear to play a previously underappreciated role in conferring protective immunity. Transcriptomic analyses of samples obtained in human challenge studies can also deepen our understanding of the immune responses preceding symptom onset, allowing characterization of innate immunity and early gene signatures, which may influence disease outcome. Influenza challenge studies demonstrate that these gene signatures have diagnostic potential in the context of pandemics, in which presymptomatic diagnosis of at-risk individuals could allow early initiation of antiviral treatment and help limit transmission. Furthermore, gene expression analysis facilitates the identification of host factors contributing to disease susceptibility, such as expression in enterotoxigenic infection. Overall, these studies highlight the exceptional value of transcriptional data generated in human challenge trials and illustrate the broad impact molecular data analysis may have on global health through rational vaccine design and biomarker discovery.
人体激发模型是让志愿者通过实验感染感兴趣的病原体，它为直接确定自然免疫和疫苗诱导免疫的保护相关因素提供了机会。在本综述中，我们强调了转录组学在人体激发研究中的应用如何有助于识别新的相关因素，并深入了解形成功能性免疫所需的免疫途径。例如，在疟疾激发试验中，固有免疫途径在赋予保护性免疫方面似乎发挥了此前未得到充分认识的作用。对人体激发研究中获取的样本进行转录组分析，还能加深我们对症状出现前免疫反应的理解，从而对固有免疫和早期基因特征进行表征，而这些特征可能会影响疾病的转归。流感激发研究表明，在大流行背景下，这些基因特征具有诊断潜力，对有风险个体进行症状前诊断可以使抗病毒治疗尽早开始，并有助于限制传播。此外，基因表达分析有助于识别导致疾病易感性的宿主因素，如产肠毒素感染中的[此处原文缺失具体内容]表达。总体而言，这些研究凸显了人体激发试验中产生的转录数据的非凡价值，并说明了分子数据分析通过合理的疫苗设计和生物标志物发现可能对全球健康产生的广泛影响。
