{"doi":"10.1101/2022.09.09.507367","title":"Amyloidogenic Propensity of Self-Assembling Peptides and their Adjuvant Potential for use as DNA Vaccines","abstract":"ABSTRACT 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 KFE 8 , compared to pathological amyloid and amyloid-like proteins α-synuclein (α-syn) and TDP-43. Further, we developed plasmid-based DNA vaccines with the KFE 8 backbone serving as a fibrillizing scaffold for delivery of a GFP model antigen. We find that expression of tandem repeats of KFE 8 is non-toxic and can be efficiently cleared by autophagy. We also demonstrate that synthetic KFE 8 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 KFE 32 -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.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2022,"id":304255,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":1,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.948,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2022-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":675059,"name":"Sheng Chen","orcid":"0000-0002-8374-136X","position":1,"is_corresponding":false},{"id":997068,"name":"Rachel D. Dreher","orcid":"0000-0002-9041-624X","position":2,"is_corresponding":false},{"id":444028,"name":"Matthew K. Howard","orcid":"0000-0002-2128-2065","position":3,"is_corresponding":false},{"id":997663,"name":"Jeremy Buck","orcid":null,"position":4,"is_corresponding":false},{"id":290107,"name":"Darren Kim","orcid":null,"position":5,"is_corresponding":false},{"id":502741,"name":"Jai S. Rudra","orcid":"0000-0002-7837-4980","position":6,"is_corresponding":false},{"id":444031,"name":"Meredith E. Jackrel","orcid":"0000-0003-4406-9504","position":7,"is_corresponding":false},{"id":997067,"name":"Paresh Shrimali","orcid":"0000-0001-6826-9039","position":0,"is_corresponding":true}],"reference_count":60,"raw_metadata":null,"created_at":"2026-07-19T00:32:32.651796Z","pmid":null,"pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}