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Review
. 2021 Oct 5;13(10):1621.
doi: 10.3390/pharmaceutics13101621.

Functionalizing Ferritin Nanoparticles for Vaccine Development

Margarida Q Rodrigues  1   2 , Paula M Alves  1   2 , António Roldão  1   2
Affiliations
Review

Functionalizing Ferritin Nanoparticles for Vaccine Development

Margarida Q Rodrigues et al. Pharmaceutics. .

Abstract

In the last decade, the interest in ferritin-based vaccines has been increasing due to their safety and immunogenicity. Candidates against a wide range of pathogens are now on Phase I clinical trials namely for influenza, Epstein-Barr, and SARS-CoV-2 viruses. Manufacturing challenges related to particle heterogeneity, improper folding of fused antigens, and antigen interference with intersubunit interactions still need to be overcome. In addition, protocols need to be standardized so that the production bioprocess becomes reproducible, allowing ferritin-based therapeutics to become readily available. In this review, the building blocks that enable the formulation of ferritin-based vaccines at an experimental stage, including design, production, and purification are presented. Novel bioengineering strategies of functionalizing ferritin nanoparticles based on modular assembly, allowing the challenges associated with genetic fusion to be circumvented, are discussed. Distinct up/down-stream approaches to produce ferritin-based vaccines and their impact on production yield and vaccine efficacy are compared. Finally, ferritin nanoparticles currently used in vaccine development and clinical trials are summarized.

Keywords: ferritin nanoparticles; genetic fusion; modular assembly; recombinant expression; surface decoration; vaccines.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Schematic overview of the topics discussed in this review: ferritin characteristics, functionalization, and recombinant expression of ferritin nanoparticles for antigen-display applications.
Figure 2
Figure 2
Native ferritin structure. Quaternary structure of human L-chain ferritin (PDB ID: 2FFX [26]), consisting of 24 subunits, assembled in octahedral (432) symmetry around the (a) 4-fold and (b) 3-fold axes. (c) Tertiary structure of human L-chain ferritin with labeled motifs: A-to-E-α helices, long (L) loop, and C- and N-terminals (C-term and N-term, respectively). Images adapted from the RCSB PDB (rcsb.org) [27] of PDB ID: 2FFX [26] created with Mol * viewer [28].
Figure 3
Figure 3
Technologies used for the design of functionalized ferritin nanoparticles. The outer surface of ferritin (Ft) nanoparticles can be functionalized with a protein of interest (POI) by genetic fusion (green-shaded) and modular assembly (blue-shaded). CID—chemically inducible dimerization.
Figure 4
Figure 4
Strategies to produce and purify recombinant ferritin. AffC: affinity chromatography; DffC: differential centrifugation; Ft: ferritin; Ft-AOI: ferritin-antigen of interest; IEC: ion-exchange chromatography; SEC: size-exclusion chromatography.
See this image and copyright information in PMC

References

    1. Karch C.P., Burkhard P. Vaccine technologies: From whole organisms to rationally designed protein assemblies. Biochem. Pharmacol. 2016;120:1–14. doi: 10.1016/j.bcp.2016.05.001. - DOI - PMC - PubMed
    1. Rehm B.H. Bioengineering towards self-assembly of particulate vaccines. Curr. Opin. Biotechnol. 2017;48:42–53. doi: 10.1016/j.copbio.2017.03.018. - DOI - PubMed
    1. Parmiani G., Castelli C., Dalerba P., Mortarini R., Rivoltini L., Marincola F.M., Anichini A. Cancer Immunotherapy With Peptide-Based Vaccines: What Have We Achieved? Where Are We Going? J. Natl. Cancer Inst. 2002;94:805–818. doi: 10.1093/jnci/94.11.805. - DOI - PubMed
    1. Yeste A., Nadeau M., Burns E.J., Weiner H.L., Quintana F.J. Nanoparticle-mediated codelivery of myelin antigen and a tolerogenic small molecule suppresses experimental autoimmune encephalomyelitis. Proc. Natl. Acad. Sci. USA. 2012;109:11270–11275. doi: 10.1073/pnas.1120611109. - DOI - PMC - PubMed
    1. Hunter Z., McCarthy D.P., Yap W.T., Harp C.T., Getts D.R., Shea L.D., Miller S.D. A Biodegradable Nanoparticle Platform for the Induction of Antigen-Specific Immune Tolerance for Treatment of Autoimmune Disease. ACS Nano. 2014;8:2148–2160. doi: 10.1021/nn405033r. - DOI - PMC - PubMed

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