{"doi":"10.1128/mbio.02256-25","title":"Immunization with peptide encapsulated within synthetic spores activates T cell responses and reduces tumor growth","abstract":"ABSTRACT Peptide-based therapeutic immunizations represent safe approaches to elicit antigen-specific T cell responses, but their broad utility remains limited due to poor immunogenicity and short in vivo stability due to rapid degradation and clearance. Here, we employed synthetic bacterial spore-like particles, “SSHELs” ( S ynthetic S pore H usk- E ncased L ipid), made entirely of biocompatible materials, to deliver a model peptide antigen in the absence of additional adjuvants. SSHELs carrying the peptide antigen were internalized by dendritic cells, and SSHEL-delivered peptides were then processed and cross-presented in vitro and in vivo more efficiently than free peptides. Furthermore, SSHEL-delivered peptides elicited effective antigen-specific T cell expansion in a manner that was dependent on particle size and peptide presentation mode (encased peptides were superior to surface-attached peptides). In a mouse melanoma model expressing the antigen ovalbumin, therapeutic immunization reduced tumor size and increased survival. We propose that SSHELs are a self-adjuvanting peptide delivery system that mimics a natural presentation to elicit a robust immune response. IMPORTANCE Effective delivery of antigens to the immune system is essential for activating the adaptive immune system. S ynthetic S pore H usk- E ncased L ipids (SSHELs) are synthetic bacterial spore-like particles, where the proteinaceous polymerized surface layer of Bacillus subtilis spores is partially reconstituted around a porous silica bead encased in a membrane. The protein surface allows easy covalent modification of the SSHEL surface, and the porous core permits high-capacity cargo loading. Here, we demonstrate that SSHELs act as a self-adjuvanting delivery system that enhances antigen uptake, processing, and MHC-I cross-presentation by dendritic cells. Importantly, we show that both particle size and antigen localization on or within the SSHEL particle profoundly influence the efficiency of T cell priming. These results establish SSHELs as a modular platform for the delivery of peptide antigens.","journal":"mBio","year":2025,"id":574776,"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":0,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9583,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2025-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1482431,"name":"Elena Tondini","orcid":"0000-0003-2915-337X","position":1,"is_corresponding":false},{"id":1106704,"name":"Federico Machinandiarena","orcid":"0000-0003-3149-9951","position":2,"is_corresponding":false},{"id":573651,"name":"Minsuk Kong","orcid":"0000-0002-6876-4520","position":3,"is_corresponding":false},{"id":1482817,"name":"Alilin Mia","orcid":null,"position":4,"is_corresponding":false},{"id":338075,"name":"Devorah Gallardo","orcid":null,"position":5,"is_corresponding":false},{"id":573655,"name":"Kandice Tanner","orcid":"0000-0002-1129-5487","position":6,"is_corresponding":false},{"id":237304,"name":"Stephen M. Hewitt","orcid":"0000-0001-8283-1788","position":7,"is_corresponding":false},{"id":573654,"name":"David Fitzgerald","orcid":"0000-0002-6589-0126","position":8,"is_corresponding":false},{"id":386064,"name":"Kumaran S. Ramamurthi","orcid":"0000-0002-2335-3568","position":9,"is_corresponding":false},{"id":1106703,"name":"Domenico D’Atri","orcid":"0000-0002-2584-984X","position":0,"is_corresponding":true}],"reference_count":47,"raw_metadata":null,"created_at":"2026-07-19T02:57:44.572630Z","pmid":"40937857","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":[]}