Peptide-based supramolecular vaccine systems

O'Neill, Conor L.; Shrimali, Paresh; Clapacs, Zain; Files, Megan; Rudra, Jai S.

doi:10.1016/j.actbio.2021.05.003

Cited by 42 publications

(31 citation statements)

References 267 publications

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“…The structure, molecular packing, and assembly of KFE 8 have been extensively characterized using spectroscopic and computational studies[7, 16, 17]. Further, we have demonstrated the ability of KFE 8 to act as an immune adjuvant in multiple preclinical models of disease[4]. Therefore, we anticipate that, barring safety concerns, the KFE 8 sequence may have broad translational utility.…”

Section: Discussionmentioning

confidence: 99%

“…A prominent strategy, inspired by viruses, is to leverage macromolecular selfassembly which facilitates the multivalent presentation of antigens, significantly enhancing immunogenicity. Recently, peptides that self-assemble into specific nanoarchitectures have been pursued as modular and chemically defined platforms for vaccine development [4]. In particular, 'amyloid-inspired' peptide nanofibers that adopt a cross-β structure have been demonstrated to be effective for efficient delivery of vaccines and immunotherapies in multiple preclinical models of infectious and non-infectious diseases [4].…”

Section: Discussionmentioning

confidence: 99%

“…Recently, peptides that self-assemble into specific nanoarchitectures have been pursued as modular and chemically defined platforms for vaccine development [4]. In particular, 'amyloid-inspired' peptide nanofibers that adopt a cross-β structure have been demonstrated to be effective for efficient delivery of vaccines and immunotherapies in multiple preclinical models of infectious and non-infectious diseases [4]. However, several unresolved challenges still remain and must be addressed to accelerate translational efforts.…”

Section: Discussionmentioning

confidence: 99%

“…Additionally, functional groups can be appended to the peptides’ N - or C -termini which are displayed in a multivalent fashion along the fibril surface, thereby imparting biofunctionality[3]. Numerous studies have demonstrated that self-assembling peptide biomaterials can support the growth of a variety of cell types, deliver therapeutic drugs, exert antimicrobial effects, serve as theranostics, and act as immune adjuvants in vaccines[1, 4, 5].…”

Section: Introductionmentioning

confidence: 99%

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Amyloidogenic Propensity of Self-Assembling Peptides and their Adjuvant Potential for use as DNA Vaccines

Shrimali

Chen

Dreher

et al. 2022

Preprint

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De novo designed peptides that self-assemble into cross-β rich fibrillar biomaterials have been pursued as an innovative platform for the development of adjuvant- and inflammation-free vaccines. However, they share structural properties similar to amyloid species implicated in neurodegenerative diseases, which has been a long-standing concern for their translation. Here, we comprehensively characterize the amyloidogenic character of the amphipathic self-assembling cross-β peptide KFE8, compared to pathological amyloid-like proteins α-synuclein (α-syn) and TDP-43. Further, we developed plasmid-based DNA vaccines with the KFE8 backbone serving as a fibrillizing scaffold for delivery of a GFP model antigen. We find that expression of tandem repeats of KFE8 is non-toxic and can be efficiently cleared by autophagy. We also demonstrate that synthetic KFE8 nanofibers do not cross-seed amyloid formation of α-syn in mammalian cells compared to α-syn preformed fibrils. In mice, vaccination with plasmids encoding the KFE32-GFP fusion protein elicited robust immune responses, inducing production of significantly higher levels of anti-GFP antibodies compared to soluble GFP or α-syn tagged GFP. Antigen-specific CD8+T cells were also detected in the spleens of vaccinated mice and cytokine profiles from antigen recall assays indicate a balanced Th1/Th2 response. These findings illustrate that cross-β-rich peptide nanofibers have distinct properties from those of pathological amyloidogenic proteins, and are an attractive platform for the development of DNA vaccines with self-adjuvanting properties and improved safety profiles.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Amyloidogenic Propensity of Self-Assembling Peptides and their Adjuvant Potential for use as DNA Vaccines

Shrimali

Chen

Dreher

et al. 2022

Preprint

Self Cite

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“…Natural nanomaterials have excellent biocompatibility and biodegradability. Several types of protein nanoparticles made of natural source proteins have been utilized for the delivery of antigens 97 . Self-assembled protein nanoparticles are promising candidates for nanovaccines.…”

Section: Administration Strategiesmentioning

confidence: 99%

Emerging vaccine nanotechnology: From defense against infection to sniping cancer

Feng

Ferdows

et al. 2022

Acta Pharmaceutica Sinica B

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Looking retrospectively at the development of humanity, vaccination is an unprecedented medical landmark that saves lives by harnessing the human immune system. During the ongoing coronavirus disease 2019 (COVID-19) pandemic, vaccination is still the most effective defense modality. The successful clinical application of the lipid nanoparticle-based Pfizer/BioNTech and Moderna mRNA COVID-19 vaccines highlights promising future of nanotechnology in vaccine development. Compared with conventional vaccines, nanovaccines are supposed to have advantages in lymph node accumulation, antigen assembly, and antigen presentation; they also have, unique pathogen biomimicry properties because of well-organized combination of multiple immune factors. Beyond infectious diseases, vaccine nanotechnology also exhibits considerable potential for cancer treatment. The ultimate goal of cancer vaccines is to fully mobilize the potency of the immune system as a living therapeutic to recognize tumor antigens and eliminate tumor cells, and nanotechnologies have the requisite properties to realize this goal. In this review, we summarize the recent advances in vaccine nanotechnology from infectious disease prevention to cancer immunotherapy and highlight the different types of materials, mechanisms, administration methods, as well as future perspectives.

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