Polymeric and Lipid Nanoparticles for Delivery of Self-Amplifying RNA Vaccines

Authors: A.K. Blakney, P.F. McKay, K. Hu, K. Samnuan, N. Jain, A. Brown, A. Thomas, P. Rogers, K. Polra, H. Sallah, J. Yeow, Y. Zhu, M.M. Stevens, A. Geall, and R.J. Shattock

Journal: Journal of Controlled Release

DOI: https://doi.org/10.1016/j.jconrel.2021.08.029

Publication - Abstract

October 10, 2021

To investigate the role of different biomaterials in self-amplifying RNA vaccines, a scientific article authored by Anna Blakney et al. 2021 at the University of British Columbia in collaboration with scientists from Precision NanoSystems Inc., and Imperial College London compared saRNA encapsulated in LNPs with saRNA encapsulated in pABOL. saRNA-LNPs were synthesized using PNI’s GenVoy-ILM™ reagent mix on the NanoAssemblr® Ignite™ platform and was compared to saRNA-pABOL, a bioreducible polymer, based on protein expression, immunogenicity, alongside humoral immune responses. The saRNA-LNPs generated by the NanoAssemblr® Ignite™ platform induced increases in acute IL6 expression, and higher antibody titres in BALB/c mice ultimately indicative of higher immunogenicity. saRNA-pABOL formulations showcased higher levels of protein expression through intramuscular administration. When these formulations were analyzed in terms of expression of the hemagglutinin (HA) glycoprotein from Influenza and the spike glycoprotein from SARS-CoV-2 based on intramuscular or intranasal routes of administration, saRNA-LNPs were found to induce robust cellular responses against SARS-CoV2, as well as Influenza leading to better reactogenicity compared to saRNA-pABOL. In conducting these comparative studies, LNPs were demonstrated to be a more potent option when optimizing saRNA vaccine formulations while pABOL formulations were more suitable for applications in protein replacement or gene therapies.

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