Functionalizing Ferritin Nanoparticles for Vaccine Development.
05 Oct 2021-Pharmaceutics (Multidisciplinary Digital Publishing Institute)-Vol. 13, Iss: 10, pp 1621
TL;DR: In this paper, a review of the building blocks that enable the formulation of ferritin-based vaccines at an experimental stage, including design, production, and purification are presented.
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.
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TL;DR: The potential of VLP-based vaccine as viable and efficient immunizing agents to induce immunity against virulent infectious agents, including, SARS-CoV-2 and protein nanoparticle-based vaccines has been elaborated and may serve as an effective alternative to conventional vaccine strategies in combating emerging infectious diseases.
Abstract: Virus-like particles (VLPs) are nanostructures that possess diverse applications in therapeutics, immunization, and diagnostics. With the recent advancements in biomedical engineering technologies, commercially available VLP-based vaccines are being extensively used to combat infectious diseases, whereas many more are in different stages of development in clinical studies. Because of their desired characteristics in terms of efficacy, safety, and diversity, VLP-based approaches might become more recurrent in the years to come. However, some production and fabrication challenges must be addressed before VLP-based approaches can be widely used in therapeutics. This review offers insight into the recent VLP-based vaccines development, with an emphasis on their characteristics, expression systems, and potential applicability as ideal candidates to combat emerging virulent pathogens. Finally, the potential of VLP-based vaccine as viable and efficient immunizing agents to induce immunity against virulent infectious agents, including, SARS-CoV-2 and protein nanoparticle-based vaccines has been elaborated. Thus, VLP vaccines may serve as an effective alternative to conventional vaccine strategies in combating emerging infectious diseases.
44 citations
TL;DR: In this article , the authors provide a brief overview of key designable features of protein nanoparticles and their implications for therapeutic delivery applications, and anticipate that protein nanarticles will rapidly grow in their prevalence and impact as clinically relevant delivery platforms.
11 citations
TL;DR: The ferritin-based nanoplatform has great potential for tumor immunotherapy, with greater possibility of clinical transformation, and three barriers (drug loading, modification sites, and animal models) are discussed.
Abstract: Ferritin is an iron storage protein that plays a key role in iron homeostasis and cellular antioxidant activity. Ferritin has many advantages as a tumor immunotherapy platform, including a small particle size that allows for penetration into tumor-draining lymph nodes or tumor tissue, a unique structure consisting of 24 self-assembled subunits, cavities that can encapsulate drugs, natural targeting functions, and a modifiable outer surface. In this review, we summarize related research applying ferritin as a tumor immune vaccine or a nanocarrier for immunomodulator drugs based on different targeting mechanisms (including dendritic cells, tumor-associated macrophages, tumor-associated fibroblasts, and tumor cells). In addition, a ferritin-based tumor vaccine expected to protect against a wide range of coronaviruses by targeting multiple variants of SARS-CoV-2 has entered phase I clinical trials, and its efficacy is described in this review. Although ferritin is already on the road to transformation, there are still many difficulties to overcome. Therefore, three barriers (drug loading, modification sites, and animal models) are also discussed in this paper. Notwithstanding, the ferritin-based nanoplatform has great potential for tumor immunotherapy, with greater possibility of clinical transformation.
7 citations
TL;DR: In this paper , the development of vaccines in broad fields ranging from conventional prophylactic vaccines against infectious diseases to therapeutic vaccines against chronic diseases and cancer providing a comprehensive overview of recent advances in eight different vaccine forms.
Abstract: Vaccines are essential public health tools and play an important role in reducing the burden of infectious diseases in the population. Emerging infectious diseases and outbreaks pose new challenges for vaccine development, requiring the rapid design and production of safe and effective vaccines against diseases with limited resources. Here, we focus on the development of vaccines in broad fields ranging from conventional prophylactic vaccines against infectious diseases to therapeutic vaccines against chronic diseases and cancer providing a comprehensive overview of recent advances in eight different vaccine forms (live attenuated vaccines, inactivated vaccines, polysaccharide and polysaccharide conjugate vaccines, recombinant subunit vaccines, virus-like particle and nanoparticle vaccines, polypeptide vaccines, DNA vaccines, and mRNA vaccines) and the therapeutic vaccines against five solid tumors (lung cancer breast cancer colorectal cancer liver cancer and gastric cancer), three infectious diseases (human immunodeficiency virus, hepatitis B virus and human papillomavirus-induced diseases) and three common chronic diseases (hypertension, diabetes mellitus and dyslipidemia). We aim to provide new insights into vaccine technologies, platforms, applications and understanding of potential next-generation preventive and therapeutic vaccine technologies paving the way for the vaccines design in the future.
5 citations
TL;DR: In this article , a cerebral infarction tissue targeted nanoparticle (CsA@HFn) was developed to treat cerebral ischemia/reperfusion injury, which is one of the main causes of death and disability in the world.
Abstract: Abstract Background Ischemic stroke is one of the main causes of death and disability in the world. The treatment for ischemic stroke is to restore blood perfusion as soon as possible. However, when ischemic brain tissue is re-perfused by blood, the mitochondrial permeability transition pore (mPTP) in neuron and microglia is excessively opened, resulting in the apoptosis of neuron and nerve inflammation. This aggravates nerve injury. Cyclosporine A (CsA) inhibits the over-opening of mPTP, subsequently reducing the release of ROS and the apoptosis of cerebral ischemia/reperfusion injured neuron and microglia. However, CsA is insoluble in water and present in high concentrations in lymphatic tissue. Herein, cerebral infarction tissue targeted nanoparticle (CsA@HFn) was developed to treat cerebral ischemia/reperfusion injury. Results CsA@HFn efficiently penetrated the blood-brain barrier (BBB) and selectively accumulated in ischemic area, inhibiting the opening of mPTP and ROS production in neuron. This subsequently reduced the apoptosis of neuron and the damage of BBB. Consequently, CsA@HFn significantly reduced the infarct area. Moreover, CsA@HFn inhibited the recruitment of astrocytes and microglia in ischemic region and polarized microglia into M2 type microglia, which subsequently alleviated the nerve inflammation. Conclusions CsA@HFn showed a significant therapeutic effect on cerebral ischemia/reperfusion injury by alleviating the apoptosis of neuron, nerve inflammation and the damage of BBB in ischemic area. CsA@HFn has great potential in the treatment of ischemic stroke. Graphical Abstract
5 citations
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TL;DR: The goals of the PDB are described, the systems in place for data deposition and access, how to obtain further information and plans for the future development of the resource are described.
Abstract: The Protein Data Bank (PDB; http://www.rcsb.org/pdb/ ) is the single worldwide archive of structural data of biological macromolecules. This paper describes the goals of the PDB, the systems in place for data deposition and access, how to obtain further information, and near-term plans for the future development of the resource.
34,239 citations
TL;DR: A great deal of research effort is now concentrated on two aspects of ferritin: its functional mechanisms and its regulation and the apparent links between iron and citrate metabolism through a single molecule with dual function are described.
2,486 citations
TL;DR: This review covers the current knowledge of fusion protein linkers and summarizes examples for their design and application and considers the general properties of linkers derived from naturally-occurring multi-domain proteins as the foundation in linker design.
1,371 citations
TL;DR: The Iron Core and Hemosiderin, the Iron-A.poferritin Interface, and other Possible Roles for Ferritin are described, as well as other possible alternatives, are described.
Abstract: PERSPECTIVES . . . . . . . . . . . ......... ... . . . .. ... ... ..... . . . . . . . . . . . ...... .... . . . . . . . . .... . 289 FERRITIN STRUCTURE 291 Apoferritin . . . . . . . . . . . . .. . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. ... . . . .. . . . . . . . . . .... .. . . 291 The Iron-A.poferritin Interface . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 297 The Iron Core and Hemosiderin . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 299 FERRITIN GENE REGULATION AND SYNTHESIS . . . . . . . . .. .. . . ........ . . . . . . .. ....... . . 300 Translational Control . . . . . . . . . . . . . . . . . ... . . . . . . . . . .. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . ....... . . . . . . . . 301 Transcriptional Control or Changes in mRNA Stability. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 302 Protein Srability . . . . . . . . . . . . . . . . . .. . . . . . . . . . . . . . . . .. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 304 Organization of Ferritin Genes . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 304 CELLULAR FERRITIN FUNCTION 306 Mechanisms: Iron Uptake and Release 306 Variations in Animal and Plant Cell Types and Microorganisms . . . . . . . . . . . . . . . . . . . . . . . 308 Other Possible Roles for Ferritin. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. . . . . . . . . . 309 CONCLUDING REMARKS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .... . . . . . . .. 3 1 0
1,278 citations
TL;DR: The robust reaction conditions and irreversible linkage of SpyTag shed light on spontaneous isopeptide bond formation and should provide a targetable lock in cells and a stable module for new protein architectures.
Abstract: Protein interactions with peptides generally have low thermodynamic and mechanical stability. Streptococcus pyogenes fibronectin-binding protein FbaB contains a domain with a spontaneous isopeptide bond between Lys and Asp. By splitting this domain and rational engineering of the fragments, we obtained a peptide (SpyTag) which formed an amide bond to its protein partner (SpyCatcher) in minutes. Reaction occurred in high yield simply upon mixing and amidst diverse conditions of pH, temperature, and buffer. SpyTag could be fused at either terminus or internally and reacted specifically at the mammalian cell surface. Peptide binding was not reversed by boiling or competing peptide. Single-molecule dynamic force spectroscopy showed that SpyTag did not separate from SpyCatcher until the force exceeded 1 nN, where covalent bonds snap. The robust reaction conditions and irreversible linkage of SpyTag shed light on spontaneous isopeptide bond formation and should provide a targetable lock in cells and a stable module for new protein architectures.
1,086 citations