Self-Assembled Ferritin Nanoparticles for Delivery of Antigens and Development of Vaccines: From Structure and Property to Applications
Abstract
:1. Introduction
2. The Function and Structure of Ferritin
2.1. Non-Heme-Binding Ferritins (Ftn)
2.2. Heme-Binding Bacterioferritins (Bfr)
2.3. DNA-Binding Proteins from Starved Cells (Dps)
3. Self-Assembled Ferritin Nanoparticles for Vaccine Development
3.1. Self-Assembly and Hetero-Polymerization of Ferritin
3.2. Engineered Ferritin-Based Vaccine
3.3. Production of Ferritin-Based Vaccine
4. Self-Assembled Ferritin Nanoparticles Display Different Types of Antigens
4.1. The Short Peptide Antigen Presented by Ferritin Nanoparticles
4.2. The Elongated Peptide Antigens Presented by Ferritin Nanoparticles
4.3. Enhancing Expression and Assembly of Ferritin Vaccines Harboring Extended Peptide Antigens in Mammalian Cells
4.4. The Bivalent Antigens Presented by Ferritin Nanoparticles
5. Molecular Mechanism of Self-Assembling Ferritin Nanoparticles to Enhance Immune Response
5.1. Ferritin Nanoparticles Activated the Inflammatory Response
5.2. Ferritin Nanoparticles Enhance Dendritic Cell Uptake
5.3. Ferritin Nanoparticles Increase the Duration of Antigen Presentation
5.4. Ferritin Nanoparticles Target Macrophages and Improve the Immune Response
6. The Advancement of Self-Assembled Ferritin Nanoparticles Vaccines Development
6.1. Self-Assembled Ferritin Nanoparticles Vaccines against Virus Infection
6.2. Self-Assembled Ferritin Nanoparticles Vaccines against Bacterial Infections
7. The Potential and Challenges of Self-Assembling Ferritin Nanoparticles in Vaccine Development
7.1. Advantage and Disadvantage of Self-Assembled Ferritin in Developing Vaccines
7.2. The Limitations and Challenges of Ferritin-Based Vaccines in Clinical Applications
8. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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Antigens | Target Pathogens | Attached Region of Ferritin | Expression System | Experiment Animal | Immunological Effects of the Ferritin Nanoparticles Vaccine | References |
---|---|---|---|---|---|---|
E protein of ZIKV | Zika virus (ZIKV) | N-terminus | E. coli | Mice | Enhanced high-affinity antigen-specific IgG antibody levels, increased secretion of the cytokines IL-4 and IFN-γ by splenocytes, significantly activated T/B lymphocytes, and improved the generation of memory T/B cells. | [78] |
E2 protein | Classical swine fever virus (CSFV) | N-terminus | SF9 cells | Rabbits | Elicited higher neutralizing antibody titers and significantly induced CSFV-specific IFN-γ-secreting cells compared to monomeric E2 protein. | [52] |
BA.5 RBD | Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) | N-terminus | Through Fc-Protein-A-tag-mediated conjugation | Golden hamsters | Stimulated strong innate and adaptive immune responses, inducing cross-neutralizing antibodies and protecting golden hamsters from multiple SARS-CoV-2 variants | [45] |
Conserved stem domain of hemagglutinin, ectodomain of matrix protein 2 | Influenza Virus | N-terminus | E. coli | Mice | Induces cross-reactive neutralizing antibodies, cellular immunity, and long-lasting memory B cell responses, offering protection against H3N2 and partial protection against H1N1. | [79] |
Three copies of extracellular domain of the transmembrane protein M2 of H1N1 | Influenza Virus | N-terminus | E. coli | Mice | Significantly activated lung CD11b dendritic cells, increased effector memory T cells and tissue-resident memory T cells in the lungs, and boosted mucosal IgG and IgA antibody production. | [57] |
Dominant B and T cell epitopes of the highly immunogenic ASFV antigen (p72, CD2v, pB602L and p30) | African swine fever virus (ASFV) | N-terminus | E. coli | Mice | The nanoparticle vaccines can induce a more robust T cell response, and the high-level antibody response against ASFV can last for more than 231 days. | [75] |
E protein domains I and II (EDI–II) of DTMUV (EDI–II-RFNp) | Duck Tembusu virus (DTMUV) | N-terminus | E. coli | Ducks | The self-assembled ferritin nanoparticles effectively protect ducks against the DTMUV challenge. | [80] |
Hemagglutinin protein | Peste des Petits Ruminants (PPR) | N-terminus | Silkworm baculovirus | Mice | The immunogenicity and protective immune response of H-Fe nanoparticle antigens expressed by silkworms were improved compared with the H antigen alone. | [81] |
Ectodomain of BPIV3 hemagglutinin-neuraminidase (HN) | Bovine parainfluenza virus type 3(BPIV3) | N-terminus | Baculovirus | Mice | The nanoparticles induced dendritic cell maturation, upregulated surface molecules, increased inflammatory cytokine secretion, and enhanced T cell activation. In mice, it induced higher titers of specific antibodies and provided better protection against BPIV3. | [82] |
Hemagglutinin | Canine distemper virus (CDV) | C-terminus | E. coli | Mice | All proteins self-assembled into nanoparticles. Vaccination induced strong, long-lasting antibody responses and anti-CDV neutralizing activity, particularly in YaH4F and YaHF groups, which also enhanced ADCC effects and induced Th1 and Th2 responses. | [83] |
E2 protein | Hepatitis C virus (HCV) | N-terminus | Drosophila Schneider 2 cell | Mice | The sE2-ferritin nanoparticle not only had nearly natural conformation but also had better affinities than the unfused sE2 to neutralizing antibodies, receptor, and patient serum. Mouse immunization studies showed that sE2-ferritin was more potent than sE2 in inducing anti-HCV broadly neutralizing antibodies. | [84] |
Inner capsid protein VP6 | Rotavirus | N-terminus | E. coli | Mice | Oral administration in mice induced strong humoral and mucosal immunity. Transgenic expression in mouse milk also induced strong immunogenicity in pups, reducing diarrhea symptoms and growth impacts. | [85] |
The trimeric N. meningitidis antigen, NadA.Two fragments of NadA(f NadA5 and NadA3) | Neisseria meningitidis | N-terminus | E. coli | Mice | In mice, the two nanoparticles elicited comparable NadA antibody levels that were 10- to 100-fold higher than those elicited by the corresponding NadA trimer subunits. Further, the NadA ferritin nanoparticles potently induced complement-mediated serum bactericidal activity. | [86] |
Type A flagellin | Pseudomonas aeruginosa (PA) | N-terminus | E. coli | Mice | A-type flagellin- ferritin nanoparticles induced a strong Th1 immune response and enhancing protection against PA strains with A-type and B-type flagellins. | [45] |
PcrV and OprI of PA | Pseudomonas aeruginosa (PA) | N-terminus | E. coli | Mice | Intramuscular immunization with nanoparticles induced quick and efficient immunity and conferred protection against PA pneumonia in mice. In addition, intranasal immunization with nanoparticles enhanced protective mucosal immunity. | [87] |
VP1 | Foot-and-mouth disease (FMD) | N-terminus | E. coli | Mice, pig | The results from guinea pigs immunized with Hpf-T34E showed that the immune efficacy was largely consistent with the immunogenicity of the FMD inactivated vaccine (IV) and could confer partial protection against FMDV challenge in guinea pigs. | [42] |
GP5 Protein | Porcine reproductive and respiratory syndrome virus (PRRSV) | N-terminus | E. coli | Mice | Ferritin (Ft) nanovaccines targeting the major glycoprotein (GP5GP5m-Ft t) exhibited the highest ELISA antibody levels, neutralizing antibody titers, the lymphocyte proliferation index, and IFN-γ levels. Furthermore, vaccination with the GP5m-Ft nanoparticle effectively protected piglets against a highly pathogenic PRRSV challenge. | [88] |
PEDV HR protein | Porcine epidemic diarrhea virus (PEDV) | N-terminus | E. coli | Mice | HR-Ferritin nanoparticles stimulated the maturation DCs and elevated the secretion of pro-inflammatory cytokines, while enhancing the uptake of antigens by DCs. | [89] |
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Cao, S.; Ma, D.; Ji, S.; Zhou, M.; Zhu, S. Self-Assembled Ferritin Nanoparticles for Delivery of Antigens and Development of Vaccines: From Structure and Property to Applications. Molecules 2024, 29, 4221. https://doi.org/10.3390/molecules29174221
Cao S, Ma D, Ji S, Zhou M, Zhu S. Self-Assembled Ferritin Nanoparticles for Delivery of Antigens and Development of Vaccines: From Structure and Property to Applications. Molecules. 2024; 29(17):4221. https://doi.org/10.3390/molecules29174221
Chicago/Turabian StyleCao, Shinuo, Dongxue Ma, Shengwei Ji, Mo Zhou, and Shanyuan Zhu. 2024. "Self-Assembled Ferritin Nanoparticles for Delivery of Antigens and Development of Vaccines: From Structure and Property to Applications" Molecules 29, no. 17: 4221. https://doi.org/10.3390/molecules29174221
APA StyleCao, S., Ma, D., Ji, S., Zhou, M., & Zhu, S. (2024). Self-Assembled Ferritin Nanoparticles for Delivery of Antigens and Development of Vaccines: From Structure and Property to Applications. Molecules, 29(17), 4221. https://doi.org/10.3390/molecules29174221