Friday, 21 June 2024 11:00am – 12:00pm

This seminar will be delivered in Lecture Theatre 4

Speaker: David Ju

Host: A/Prof. Markus Muellner

Title: PEG immunogenicity of mRNA vaccines and their influence on nanomedicine targeting in human

Abstract: Understanding the interactions of nanoengineered particles with specific proteins and cells is necessary to unlock their medicinal utility.1,2 Upon exposure to biological fluids, nanoparticles adsorb proteins, lipids and nucleic acids, resulting in the formation of a “biomolecular corona”. This corona modulates downstream biological responses, including recognition by immune cells. Resolving the complexity of human plasma has been a major barrier to understanding the role of corona on biological response. We have previously engineered poly(ethylene glycol) (PEG) nanoparticles and investigated the formation of personalized biomolecular coronas on particles using plasma from a cohort of healthy donors and their impact on particle–immune cell interactions using an ex vivo human blood assay.3,4 We demonstrated that the enrichment of immunoglobulins and complement proteins in biomolecular coronas is correlated with donor-specific nanoparticle association with human blood immune cells.4 We further demonstrated that the protein corona composition can be modulated by particle building blocks and protein pre-coatings.5,6 Built on the previous works, we have recently studied the boost of poly(ethylene glycol) (PEG)-specific antibodies by SARS-CoV-2 mRNA lipid nanoparticle (LNP) vaccines.7 After studying plasma samples from 130 adults, we discovered that anti-PEG antibodies were significantly boosted by mRNA-1273 vaccine and to a lower extent by BNT162b2 vaccines. We found that anti-PEG antibodies have a significant impact on PEGylated nanoparticle−immune cell interactions in human blood. Our study addresses timely and important questions regarding the anti-PEG antibody responses in healthy adults following SARS-CoV-2 mRNA-LNP vaccination and whether the induced anti-PEG antibody may impact the fate of other PEG-containing nanomedicines.8 In this seminar, I will talk about our recent studies on the pharmacokinetics of mRNA lipid nanoparticle vaccine in humans and an ex vivo human leukemia blood model to assess the targeting of nanomedicine.

References

1) Ju, Y. #; Kim, C.-J.#; Caruso, F.* Functional Ligand-Enabled Particle Assembly for Bio–Nano Interactions. Acc. Chem. Res. 2023, 56, 1826.

2) Ju, Y.#; Liao, H.#; Richardson, J. J.; Guo, J.*; Caruso, F.* Nanostructured Particles Assembled from Natural Building Blocks for Advanced Therapies. Chem. Soc. Rev. 2022, 51, 4287.

3) Li, S.; Ma, Y.; Cui, J.; Caruso, F.; Ju, Y.*, Engineering poly(ethylene glycol) particles for targeted drug delivery. Chem. Commun. 2024, 60, 2591.

4) Ju, Y.; Kelly, H. G.; Dagley, L. F.; Reynaldi, A.; Schlub, T. E.; Spall, S. K.; Bell, C. A.; Cui, J.; Mitchell, A. J.; Lin, Z.; Wheatley, A. K.; Thurecht, K. J.; Davenport, M. P.; Webb, A. I.; Caruso, F.*; Kent, S. J.* Person-Specific Biomolecular Coronas Modulate Nanoparticle Interactions with Immune Cells in Human Blood. ACS Nano 2020, 14, 15723-15737.

5) Song, J.; Ju, Y.; Amarasena, T. H.; Lin, Z.; Mettu, S.; Zhou, J.; Rahim, M. A.; Ang, C.-S.; Cortez-Jugo, C.; Kent, S. J.*; Caruso, F.* Influence of Poly(Ethylene Glycol) Molecular Architecture on Particle Assembly and Ex Vivo Particle–Immune Cell Interactions in Human Blood. ACS Nano 2021, 15, 10025-10038.

6) Li, S.; Ju, Y.*; Zhou, J.; Faria, M.; Ang, C.-S.; Mitchell, A.; Zhong, Q.-Z.; Zheng, T.; Kent, S. J.*; Caruso, F.*, Protein Precoating Modulates Biomolecular Coronas and Nanocapsule–Immune Cell Interactions in Human Blood. J. Mater. Chem. B 2022, 10, 7607–7621.

7) Ju, Y.*; Lee, W. S.; Pilkington, E. H.; Kelly, H. G.; Li, S.; Selva, K. J.; Wragg, K. M.; Subbarao, K.; Nguyen, T. H. O.; Rowntree, L. C.; Allen, L. F.; Bond, K.; Williamson, D. A.; Truong, N. P.; Plebanski, M.; Kedzierska, K.; Mahanty, S.; Chung, A. W.; Caruso, F.; Wheatley, A. K.; Juno, J. A.; Kent, S. J.* Anti-PEG Antibodies Boosted in Humans by SARS-CoV-2 Lipid Nanoparticle mRNA Vaccine. ACS Nano 2022, 16, 11769–11780.

8) Ju, Y.; Carreño, J. M.; Simon V.; Dawson K.; Krammer F.*; Kent, S. J.* Impact of Anti-PEG Antibodies Induced by SARS-CoV-2 mRNA Vaccines. Nat. Rev. Immunol. 2023, 23, 135–136.

* denotes corresponding authors; # denotes equal contributions

Bio: Yi (David) Ju is an ARC Discovery Early Career Researcher Award (DECRA) Fellow at RMIT University. His research interests include both fundamental bio–nano interaction studies (i.e., interactions between nanomaterials and the immune system) and translational research on developing novel nanoparticles for targeted drug and gene delivery. David’s work has been pioneering in different aspects of materials science and nanotechnology. For example, his study has demonstrated that personalized biomolecular coronas can modulate nanoparticle–immune cell interactions in human blood (ACS Nano 2020) and that the mRNA lipid nanoparticle vaccines developed for SARS-CoV-2 can induce a polymer-specific antibody in human blood (ACS Nano 2022 and Nat. Rev. Immunol. 2023). He has received several awards (e.g., Victoria Fellowship, ACIS ECR lectureship, Most Significant CBNS Publication Award) and secured $2 M ($1.3 M as a lead CI) in fellowship and research funding in the last 5 years, including ARC DECRA fellowship, RMIT Vice-Chancellor’s Postdoctoral Fellowship, mRNA Victoria Research Acceleration Fund, Victorian Critical Vaccinees Collection COVID-19 Research Seed Funding Grant, Maxwell Eagle Endowment Award for Cancer Research, University of Melbourne Early Career Researcher Grant, and ARC Discovery Project. His research has led to 66 referred journal publications with >3400 Scopus citations and an average FWCI of 3.44. He currently serves as an Editor for the Journal of Materials Science and committee member of Victorian Branch of Royal Australian Chemical Institute (RACI).