Doubovetzky Michel, Ataman-Önal Yasemin, Chousterman Benjamin, Feroldi Emmanuel, Garçon Nathalie, Grillet Marie-Hélène, Kramer Daniel, Laurent Sébastien, Lewis David J M, Luna Ernesto, Manigold Tobias, Syntin Patrick, Burdin Nicolas, Fraisse Laurent, Jackson Nicholas
Sanofi R&D, 1541 Avenue Marcel Mérieux, 69280 Marcy-l'Étoile, France.
Département d'Anesthésie-Réanimation-SMUR, Lariboisière Hospital, Paris, France.
Vaccine. 2020 Dec 3;38(51):8055-8063. doi: 10.1016/j.vaccine.2020.10.015. Epub 2020 Nov 10.
Vaccines prevent infectious diseases, but vaccination is not without risk and adverse events are reported although they are more commonly reported for biologicals than for vaccines. Vaccines and biologicals must undergo vigorous assessment before and after licensure to minimise safety concerns. Potential safety concerns should be identified as early as possible during the development for vaccines and biologicals to minimize investment risk. State-of-the art tools and methods to identify safety concerns and biomarkers that are predictive of clinical outcomes are indispensable. For vaccines and adjuvant formulations, systems biology approaches, supported by single-cell microfluidics applied to translational studies between preclinical and clinical studies, could improve reactogenicity and safety predictions. Next-generation animal models for clinical assessment of injection-site reactions with greater relevance for target human population and criteria to define the level of acceptability of local reactogenicity at vaccine injection sites in pre-clinical animal species should be assessed. Advanced in silico machine-learning-based analytics, species-specific cell or tissue expression, receptor occupancy and kinetics and cell-based assays for functional activity are needed to improve pre-clinical safety assessment of biologicals. The in vitro MIMIC® system could be used to compliment preclinical and clinical studies for assessing immune-toxicity, immunogenicity, immuno-inflammatory and mode of action of biologicals and vaccines. Sanofi Pasteur brought together leading experts in this field to review the state-of-the-art at a unique 'Safety Biomarkers Symposium' on 28-29 November 2017. Here we summarise the proceedings of this symposium. This unique scientific meeting confirmed the importance for institutions and industrial organizations to collaborate to develop tools and methods needed for predicting reactogenicity and immune-inflammatory reactions to vaccines and biologicals, and to develop more accuracy, reliability safety biomarkers, to inform decisions on the attrition or advancement of vaccines and biologicals.
疫苗可预防传染病，但接种疫苗并非毫无风险，尽管生物制品比疫苗更常报告不良事件，但疫苗接种的不良事件也有报告。疫苗和生物制品在获得许可前后必须经过严格评估，以尽量减少安全问题。在疫苗和生物制品的研发过程中，应尽早识别潜在的安全问题，以降低投资风险。识别安全问题和预测临床结果的生物标志物的先进工具和方法是必不可少的。对于疫苗和佐剂配方，单细胞微流控技术支持的系统生物学方法应用于临床前和临床研究之间的转化研究，可以改善反应原性和安全性预测。应评估与目标人群相关性更高的用于临床评估注射部位反应的新一代动物模型，以及定义临床前动物物种疫苗注射部位局部反应原性可接受水平的标准。需要基于计算机的先进机器学习分析、物种特异性细胞或组织表达、受体占有率和动力学以及功能活性的细胞检测方法，以改善生物制品的临床前安全性评估。体外MIMIC®系统可用于补充临床前和临床研究，以评估生物制品和疫苗的免疫毒性、免疫原性、免疫炎症和作用方式。赛诺菲巴斯德在2017年11月28日至29日举行的独特的“安全生物标志物研讨会”上召集了该领域的顶尖专家，以回顾最新技术。在此，我们总结了本次研讨会的会议记录。这次独特的科学会议证实了机构和产业组织合作开发预测疫苗和生物制品反应原性和免疫炎症反应所需工具和方法的重要性，并开发更准确、可靠的安全生物标志物，为疫苗和生物制品的淘汰或推进决策提供依据。
