Data availability
The datasets generated during and/or analysed during the current study are available from the corresponding author on reasonable request.
References
-
Aguzzi, A., Nuvolone, M. & Zhu, C. The immunobiology of prion diseases. Nat. Publish Group. https://doi.org/10.1038/nri3553 (2013).
-
Zerr, I. et al. Creutzfeldt–Jakob disease and other prion diseases. Nat. Reviews Disease Primers Vol. 10 (1), 1–16. https://doi.org/10.1038/s41572-024-00497-y (2024).
-
Prusiner, S. B. Prion 1998 Prusiner. Proc. Natl. Acad. Sci. U S A. 95, 13363–13383. https://doi.org/10.1073/pnas.95.23.13363 (2025).
-
Napper, S. & Schatzl, H. M. Vaccines for prion diseases: a realistic goal?. Springer science and business media deutschland GmbH. https://doi.org/10.1007/s00441-023-03749-7 (2023).
-
Napper, S. & Schatzl, H. M. Oral vaccination as a potential strategy to manage chronic wasting disease in wild Cervid populations. Front. Media S A https://doi.org/10.3389/fimmu.2023.1156451 (2023).
-
Taki, A. & Smooker, P. Small wonders—the use of nanoparticles for delivering antigen. MDPI AG. https://doi.org/10.3390/vaccines3030638 (2015).
-
Abdelaziz, D. H. et al. Immunization of cervidized Transgenic mice with multimeric deer prion protein induces self-antibodies that antagonize chronic wasting disease infectivity in vitro. https://doi.org/10.1038/s41598-017-11235-8
-
Abdelaziz, D. H. et al. Recombinant prion protein vaccination of Transgenic elk PrP mice and reindeer overcomes self-tolerance and protects mice against chronic wasting disease. J. Biol. Chem. 293 (51), 19812–19822. https://doi.org/10.1074/jbc.RA118.004810 (2018).
-
Uskoković, V. Nanomedicine for the poor: A lost cause or an Idea whose time has yet to come? Future Med. Ltd. https://doi.org/10.2217/nnm-2021-0024 (2021).
-
Cao, P., Xu, Z. P. & Li, L. Tailoring functional nanoparticles for oral vaccine delivery: recent advances and future perspectives. Compos. B Eng. 236, 109826. https://doi.org/10.1016/J.COMPOSITESB.2022.109826 (2022).
-
Cai, K. et al. Dimeric drug polymeric nanoparticles with exceptionally high drug loading and quantitative loading efficiency. J. Am. Chem. Soc. 137 (10), 3458–3461. https://doi.org/10.1021/JA513034E (2015).
-
Alsaab, H. O. et al. PLGA-based nanomedicine: History of advancement and development in clinical applications of multiple diseases. Pharmaceutics 14 (12), https://doi.org/10.3390/PHARMACEUTICS14122728 (2022).
-
des Rieux, A., Fievez, V., Garinot, M., Schneider, Y. J. & Préat, V. Nanoparticles as potential oral delivery systems of proteins and vaccines: A mechanistic approach. J. Controlled Release. 116 (1), 1–27. https://doi.org/10.1016/j.jconrel.2006.08.013 (2006).
-
Lagreca, E. et al. Recent advances in the formulation of PLGA microparticles for controlled drug delivery. Prog. Biomater. 9 (4), 153–174 https://doi.org/10.1007/S40204-020-00139-Y (2020).
-
Ghitman, J., Biru, E. I., Stan, R. & Iovu, H. Review of hybrid PLGA nanoparticles: future of smart drug delivery and theranostics medicine. Mater. Des. 193, 108805. https://doi.org/10.1016/J.MATDES.2020.108805 (2020).
-
Omidian, H., Wilson, R. L. & Castejon, A. M. Recent advances in Peptide-Loaded PLGA nanocarriers for drug delivery and regenerative medicine. Pharmaceuticals https://doi.org/10.3390/PH18010127 (2025).
-
Garinot, M. et al. PEGylated PLGA-based nanoparticles targeting M cells for oral vaccination. J. Controlled Release. 120 (3), 195–204. https://doi.org/10.1016/j.jconrel.2007.04.021 (2007).
-
Ma, L. J. et al. Quantitative evaluation of cellular internalization of polymeric nanoparticles within laryngeal cancer cells and immune cells for enhanced drug delivery. Nanoscale Res. Lett. https://doi.org/10.1186/s11671-021-03498-y (2021).
-
Cruz, K. P. et al. Development and characterization of PLGA nanoparticles containing 17-DMAG, an Hsp90 inhibitor. Front. Chem. 9, 644827 https://doi.org/10.3389/FCHEM.2021.644827/BIBTEX (2021).
-
Salvador, A. et al. Design and evaluation of surface and adjuvant modified PLGA microspheres for uptake by dendritic cells to improve vaccine responses. Int. J. Pharm. 496 (2), 371–381. https://doi.org/10.1016/j.ijpharm.2015.10.037 (2015).
-
Sivadasan, D., Sultan, M. H., Madkhali, O., Almoshari, Y. & Thangavel, N. ‘Polymeric lipid hybrid nanoparticles (Plns) as emerging drug delivery platform—a comprehensive review of their properties, preparation methods, and therapeutic applications. Pharmaceutics https://doi.org/10.3390/PHARMACEUTICS13081291 (2021).
-
Xu, J. et al. Controllable microfluidic production of Drug-Loaded PLGA nanoparticles using partially water-miscible mixed solvent microdroplets as a precursor. Sci. Rep. 7 (1), 1–12 (2017).
-
Hernández-Giottonini, K. Y. et al. ‘PLGA nanoparticle preparations by emulsification and nanoprecipitation techniques: effects of formulation parameters. Royal Soc. Chem. https://doi.org/10.1039/c9ra10857b (2020).
-
Anand, U., Lu, J., Loh, D., Aabdin, Z. & Mirsaidov, U. Hydration Layer-Mediated pairwise interaction of nanoparticles. Nano Lett. 16 (1), 786–790. https://doi.org/10.1021/ACS.NANOLETT.5B04808 (2016).
-
Elsutohy, M. M., Selo, A., Chauhan, V. M., Tendler, S. J. B. & Aylott, J. W. Enhanced distance-dependent fluorescence quenching using size tuneable core shell silica nanoparticles. RSC Adv. 8, 62, 35840–35848 https://doi.org/10.1039/C8RA05929B (2018).
-
Kaiser-Schulz, G. et al. Polylactide-Coglycolide microspheres coencapsulating Recombinant tandem prion protein with CpG-Oligonucleotide break Self-Tolerance to prion protein in Wild-Type mice and induce CD4 and CD8 T cell responses. 1 https://www.jimmunol.org. (2007).
-
Gilch, S. et al. Chronic wasting disease. Top. Curr. Chem. 305, 51–78. https://doi.org/10.1007/128_2011_159 (2011).
-
Dölen, Y. et al. PLGA nanoparticles Co-encapsulating NY-ESO-1 peptides and IMM60 induce robust CD8 and CD4 T cell and B cell responses. Front. Immunol. https://doi.org/10.3389/fimmu.2021.641703 (2021).
-
Silva, A. L., Soema, P. C., Slütter, B., Ossendorp, F. & Jiskoot, W. ‘PLGA particulate delivery systems for subunit vaccines: linking particle properties to immunogenicity. https://doi.org/10.1080/21645515.2015.1117714 (Taylor and Francis inc., 2016).
-
Rajapaksa, T. E., Stover-Hamer, M., Fernandez, X., Eckelhoefer, H. A. & Lo, D. D. Claudin 4-targeted protein incorporated into PLGA nanoparticles can mediate M cell targeted delivery. J. Controlled Release 142 (2), 196–205. https://doi.org/10.1016/J.JCONREL.2009.10.033 (2010).
-
Bachmann, M. F. & Jennings, G. T. Vaccine delivery: A matter of size, geometry. Kinet. Mol. Patterns https://doi.org/10.1038/nri2868 (2010).
-
Allahyari, M. et al. Co-delivery of PLGA nanoparticles loaded with rSAG1 antigen and TLR ligands: an 1 efficient vaccine against chronic toxoplasmosis 2 3’. https://www.elsevier.com/open-access/userlicense/1.0/ (2021).
-
Danhier, F. et al. PLGA-based nanoparticles: an overview of biomedical applications. J. Controlled Release. 161 (2), 505–522. https://doi.org/10.1016/j.jconrel.2012.01.043 (2012).
-
Storni, T. et al. Nonmethylated CG motifs packaged into Virus-Like particles induce protective cytotoxic T cell responses in the absence of systemic side effects. J. Immunol. 172 (3), 1777–1785. https://doi.org/10.4049/jimmunol.172.3.1777 (2004).
-
Ishii, K. J. & Akira, S. Toll or toll-free adjuvant path toward the optimal vaccine development. https://doi.org/10.1007/s10875-007-9087-x (2007).
-
Yang, J. et al. Recent applications of PLGA in drug delivery systems. Multidiscip. DigiT. Publish. Inst. (MDPI). https://doi.org/10.3390/polym16182606 (2024).
-
Guidelines on stability evaluation of vaccines. https://www.who.int/biologicals (2006).
-
Goñi, F. et al. Mucosal immunization with an attenuated Salmonella vaccine partially protects white-tailed deer from chronic wasting disease. Vaccine 33 (5), 726–733 https://doi.org/10.1016/j.vaccine.2014.11.035 (2015).
-
Church, J. A. et al. Predictors of oral rotavirus vaccine immunogenicity in rural Zimbabwean infants. Vaccine 38 (13), 2870 https://doi.org/10.1016/J.VACCINE.2020.01.097 (2020).
-
Patriarca, P. A., Wright, P. F. & John, T. J. Factors affecting the immunogenicity of oral poliovirus vaccine in developing countries: review. Rev. Infect. Dis. 13 (5), 926–939. https://doi.org/10.1093/CLINIDS/13.5.926 (1991).
-
Neutra, M. R. & Kozlowski, P. A. Mucosal vaccines: The promise and the challenge. https://doi.org/10.1038/nri1777 (2006).
-
Gilch, S. et al. Polyclonal anti-PrP auto-antibodies induced with dimeric PrP interfere efficiently with PrPSc propagation in prion-infected cells. J. Biol. Chem. 278 (20), 18524–18531. https://doi.org/10.1074/jbc.M210723200 (2003).
-
Ertmer, A. et al. The tyrosine kinase inhibitor STI571 induces cellular clearance of PrP Sc in prion-infected cells. J. Biol. Chem. 279 (40), 41918–41927. https://doi.org/10.1074/jbc.M405652200 (2004).
Funding
We acknowledge funding for this research from NSERC (Alliance Grant ALLRP 571218-21), Alberta Conservation Association, Office of the Chief Scientist, Alberta Environment and Protected Areas, Saskatchewan Ministry of Environment, and Parks Canada Agency. In-kind contributions were provided by the Canadian Food Inspection Agency, The Canadian Agri-Food Policy Institute, National Boreal Caribou Knowledge Consortium, and Métis Nation of Alberta. We are grateful for financial support from NSERC (RGPIN-2020-04581), RDAR, Alberta Innovates (201600023; 222300851) and NIH (R01AI156037).
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Elsutohy, M.M., Abdelaziz, D., Dalton, C.S. et al. PLGA nanoparticles for oral delivery of prion-specific antigen: a novel approach to chronic wasting disease vaccination. Sci Rep (2025). https://doi.org/10.1038/s41598-025-31381-8
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DOI: https://doi.org/10.1038/s41598-025-31381-8
