{"doi":"10.1101/2024.10.22.619692","title":"Engineered protein destabilization reverses intrinsic immune evasion for candidate vaccine pan-strain KSHV and SARS-CoV-2 antigens","abstract":"Abstract Both Kaposi sarcoma herpesvirus LANA and SARS coronavirus 2 RdRp/nsp12 are highly conserved replication proteins that evade immune processing. By deleting the LANA central repeat 1 domain (LANA ΔCR1 ) or by dividing RdRp into two separated fragments (RdRp Frag ) to maximize nascent protein mis-folding, cis peptide presentation was increased. Native LANA or RdRp SIINFEKL fusion proteins expressed in MC38 cancer cells were not recognized by activated OT-1 CD8 + cells against SIINFEKL but cytotoxic recognition was restored by expression of the corresponding modified proteins. Immunocompetent syngeneic mice injected with LANA- or RdRp-SIINFEKL MC38 cells developed rapidly-growing tumors with short median survival times. Mice injected with LANA ΔCR1 - or RdRp Frag -SIINFEKL had partial tumor regression, slower tumor growth, longer median survival, as well as increased effector-specific tumor-infiltrating lymphocytes. These mice developed robust T cell responses lasting at least 90 days post-injection that recognized native viral protein epitopes. Engineered vaccine candidate antigens can unmask virus-specific CTL responses that are typically suppressed during native viral infection.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2024,"id":489182,"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":2,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9477,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2024-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":282225,"name":"Bingxian Xie","orcid":"0000-0001-9816-2670","position":1,"is_corresponding":false},{"id":914259,"name":"Masahiro Shuda","orcid":"0000-0003-0595-2572","position":2,"is_corresponding":false},{"id":237079,"name":"Greg M. Delgoffe","orcid":"0000-0002-2957-8135","position":3,"is_corresponding":false},{"id":51648,"name":"Yuan Chang","orcid":"0000-0003-1125-4041","position":4,"is_corresponding":false},{"id":343734,"name":"Patrick S. Moore","orcid":"0000-0002-8132-858X","position":5,"is_corresponding":false},{"id":561954,"name":"Li Wan","orcid":"0000-0002-9797-0315","position":0,"is_corresponding":true}],"reference_count":65,"raw_metadata":null,"created_at":"2026-07-19T02:08:23.929823Z","pmid":"39484438","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":[]}