Attachment of flagellin enhances the immunostimulatory activity of a hemagglutinin-ferritin nano-cage

Lee, Emerson B.; Hm, Jeon; Kim, Chang-Ung; Park, Sang M.; Cho, Geunyoung; Kim, Hyun‐Jin; Kim, Young‐Jin; Kim, Doo‐Jin; Kim, Young S.; Lee, Hayyoung; Lee, Jie‐Oh

doi:10.1016/j.nano.2019.01.012

Cited by 11 publications

(9 citation statements)

References 60 publications

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“…For example, CpG-gp-E2 dodecahedral cages incorporating the TLR-9 ligand CpG (Table 1) were shown to induce an enhanced cell-mediated response compared to gp-E2 nanoparticles coadministered with soluble CpG [79]. Furthermore, modular co-assembly of ferritin-HA and ferritinflagellin, a known TLR5 ligand, revealed robust protection against influenza viral challenge without the use of other adjuvants [209]. Compared to ferritin-HA nanoparticles only, incorporation of flagellin enhanced the humoral and the cell-mediated immune responses.…”

Section: Modulating Immune Responses With Tailored Protein Nanostructmentioning

confidence: 99%

Protein Supramolecular Structures: From Self-Assembly to Nanovaccine Design

et al. 2020

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Life-inspired protein supramolecular assemblies have recently attracted considerable attention for the development of next-generation vaccines to fight against infectious diseases, as well as autoimmune diseases and cancer. Protein self-assembly enables atomic scale precision over the final architecture, with a remarkable diversity of structures and functionalities. Self-assembling protein nanovaccines are associated with numerous advantages, including biocompatibility, stability, molecular specificity and multivalency. Owing to their nanoscale size, proteinaceous nature, symmetrical organization and repetitive antigen display, protein assemblies closely mimic most invading pathogens, serving as danger signals for the immune system. Elucidating how the structural and physicochemical properties of the assemblies modulate the potency and the polarization of the immune responses is critical for bottom-up design of vaccines. In this context, this review briefly covers the fundamentals of supramolecular interactions involved in protein self-assembly and presents the strategies to design and functionalize these assemblies. Examples of advanced nanovaccines are presented, and properties of protein supramolecular structures enabling modulation of the immune responses are discussed. Combining the understanding of the self-assembly process at the molecular level with knowledge regarding the activation of the innate and adaptive immune responses will support the design of safe and effective nanovaccines.

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Section: Modulating Immune Responses With Tailored Protein Nanostructmentioning

confidence: 99%

Protein Supramolecular Structures: From Self-Assembly to Nanovaccine Design

et al. 2020

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“…The effectiveness of ferritin-haemagglutinin nanocages as vaccine candidates against influenza virus has been described. [83][84][85] By analogy, ferritin nanocages furnished with S glycoprotein or its RBD could potentially induce a broad neutralizing antibody response against SARS-CoV-2. On the other hand, available data show that ferritin-antibody conjugates are effective in targeting cancer cells.…”

Section: Discussionmentioning

confidence: 99%

“…[82] This approach has been successfully used for few other viruses. It is shown that bacterial or insect ferritin nanocages can be furnished with multiple native-like homotrimeric haemagglutinin protein of influenza [83][84][85] or HIV-1 envelope glycoprotein, [86] or with the homotrimers of different parts of the haemagglutinin. [87,88] These nanocages elicit broad neutralizing antibody response.…”

Section: Mosaic Nanocages As Vaccine Candidatementioning

confidence: 99%

Ferritin as a Platform for Creating Antiviral Mosaic Nanocages: Prospects for Treating COVID‐19

Ebrahimi

2020

ChemBioChem

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Infectious diseases are a continues threat to human health and the economy worldwide. The latest example is the global pandemic of COVID-19 caused by SARS-CoV-2. Antibody therapy and vaccines are promising approaches to treat the disease; however, they have bottlenecks: they might have low efficacy or narrow breadth due to the continuous emergence of new strains of the virus or antibodies could cause antibodydependent enhancement (ADE) of infection. To address these bottlenecks, I propose the use of 24-meric ferritin for the

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“…The effectiveness of E2 nanoparticles was confirmed using preclinical melanoma and HIV-1 vaccines [254][255][256][257]. Lee and coworkers have described nanocages derived from bacterial ferritin or the artificial cage protein I3-01 as carriers for the TLR5 agonist protein FliC or a truncated variant (ΔFliC) lacking the Naip5 inflammasome-activating domain D0, as well as protective antigen from Bacillus anthracis or influenza HA [258]. Mice vaccinated with HA-and ΔFliC-conjugated nanocages demonstrated 100% survival after H1N1 influenza challenge and clinical observations improved on par with the 2016-2017 quadrivalent inactivated influenza vaccine.…”

Section: Adaptive Immune Responses To Protein Subunit Nanoparticlesmentioning

confidence: 98%

Peptide-Based Supramolecular Vaccine Systems

et al. 2021

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Currently approved replication-competent and inactivated vaccines are limited by excessive reactogenicity and poor safety profiles, while subunit vaccines are often insufficiently immunogenic without co-administering exogenous adjuvants. Self-assembling peptide-, peptidomimetic-, and protein-based biomaterials offer a means to overcome these challenges through their inherent modularity, multivalency, and biocompatibility. As these scaffolds are biologically derived and present antigenic arrays reminiscent of natural viruses, they are prone to immune recognition and are uniquely capable of functioning as self-adjuvanting vaccine delivery vehicles that improve humoral and cellular responses. Beyond this intrinsic immunological advantage, the wide range of available amino acids allows for facile de novo design or straightforward modifications to existing sequences. This has permitted the development of vaccines and immunotherapies tailored to specific disease models, as well as generalizable platforms that have been successfully applied to prevent or treat numerous infectious and non infectious diseases. In this review, we briefly introduce the immune system, discuss the structural determinants of coiled coils, β-sheets, peptide amphiphiles, and protein subunit nanoparticles, and highlight the utility of these materials using notable examples of their innate and adaptive immunomodulatory capacity.

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Attachment of flagellin enhances the immunostimulatory activity of a hemagglutinin-ferritin nano-cage

Cited by 11 publications

References 60 publications

Protein Supramolecular Structures: From Self-Assembly to Nanovaccine Design

Protein Supramolecular Structures: From Self-Assembly to Nanovaccine Design

Ferritin as a Platform for Creating Antiviral Mosaic Nanocages: Prospects for Treating COVID‐19

Peptide-Based Supramolecular Vaccine Systems

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