Screening of Oligomeric (Meth)acrylate Vaccine Adjuvants Synthesized via Catalytic Chain Transfer Polymerization

通过催化链转移聚合合成的寡聚(甲基)丙烯酸酯疫苗佐剂的筛选

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作者:Cordula S Hege, Amy Stimpson, Joseph Sefton, James Summers, Helena Henke, Adam A Dundas, Tony Phan, Robert Kinsey, Jeffrey A Guderian, Sandra J Sivananthan, Raodoh Mohamath, William R Lykins, Gabi Ramer-Denisoff, Susan Lin, Christopher B Fox, Derek J Irvine

Abstract

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.

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