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

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.

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.

Citation

Hege, C. S., Stimpson, A., Sefton, J., Summers, J., Henke, H., Dundas, A. A., Phan, T., Kinsey, R., Guderian, J. A., Sivananthan, S. J., Mohamath, R., Lykins, W. R., Ramer-Denisoff, G., Lin, S., Fox, C. B., & Irvine, D. J. (2023). Screening of Oligomeric (Meth)acrylate Vaccine Adjuvants Synthesized via Catalytic Chain Transfer Polymerization. Polymers, 15(18), Article 3831. https://doi.org/10.3390/polym15183831

• Journal Article Type: Article
• Acceptance Date: Sep 14, 2023
• Online Publication Date: Sep 20, 2023
• Publication Date: 2023-09
• Deposit Date: Oct 25, 2023
• Publicly Available Date: Oct 26, 2023
• Journal: Polymers
• Electronic ISSN: 2073-4360
• Publisher: MDPI
• Peer Reviewed: Peer Reviewed
• Volume: 15
• Issue: 18
• Article Number: 3831
• DOI: https://doi.org/10.3390/polym15183831
• Keywords: polymerization; screening; catalytic chain transfer; vaccine; adjuvant; squalene
• Public URL: https://nottingham-repository.worktribe.com/output/25394517