Hege Cordula S, Stimpson Amy, Sefton Joseph, Summers James, Henke Helena, Dundas Adam A, Phan Tony, Kinsey Robert, Guderian Jeffrey A, Sivananthan Sandra J, Mohamath Raodoh, Lykins William R, Ramer-Denisoff Gabi, Lin Susan, Fox Christopher B, Irvine Derek J
Centre for Additive Manufacturing, Department of Chemical and Environmental Engineering, University of Nottingham, Nottingham NG7 2RD, UK.
School of Chemistry, University of Nottingham, Nottingham NG7 2RD, UK.
Polymers (Basel). 2023 Sep 20;15(18):3831. doi: 10.3390/polym15183831.
This report details the first systematic screening of free-radical-produced methacrylate oligomer reaction mixtures as alternative vaccine adjuvant components to replace the current benchmark compound squalene, which is unsustainably sourced from shark livers. Homo-/co-oligomer mixtures of methyl, butyl, lauryl, and stearyl methacrylate were successfully synthesized using catalytic chain transfer control, where the use of microwave heating was shown to promote propagation over chain transfer. Controlling the mixture material properties allowed the correct viscosity to be achieved, enabling the mixtures to be effectively used in vaccine formulations. Emulsions of selected oligomers stimulated comparable cytokine levels to squalene emulsion when incubated with human whole blood and elicited an antigen-specific cellular immune response when administered with an inactivated influenza vaccine, indicating the potential utility of the compounds as vaccine adjuvant components. Furthermore, the oligomers' molecular sizes were demonstrated to be large enough to enable greater emulsion stability than squalene, especially at high temperatures, but are predicted to be small enough to allow for rapid clearance from the body.
本报告详细介绍了首次对自由基产生的甲基丙烯酸酯低聚物反应混合物进行系统筛选，以替代目前的基准化合物角鲨烯作为疫苗佐剂成分，角鲨烯来自鲨鱼肝脏，其来源不可持续。使用催化链转移控制成功合成了甲基丙烯酸甲酯、丁酯、月桂酯和硬脂酯的均聚物/共聚物混合物，其中微波加热的使用显示出促进链增长而非链转移。控制混合物的材料特性可实现正确的粘度，使混合物能够有效地用于疫苗配方。当与人类全血一起孵育时，所选低聚物的乳液刺激产生的细胞因子水平与角鲨烯乳液相当，并且当与灭活流感疫苗一起施用时引发抗原特异性细胞免疫反应，表明这些化合物作为疫苗佐剂成分的潜在用途。此外，已证明低聚物分子尺寸足够大，能够比角鲨烯具有更高的乳液稳定性，尤其是在高温下，但预计又足够小，以便能从体内快速清除。
