{"doi":"10.1126/sciadv.adx0037","title":"Conserved CD8 T cell vaccines without B cell epitopes drive robust protection against SARS-CoV-2 that is enhanced by intranasal boost","abstract":"The emergence of SARS-CoV-2 variants has challenged the current spike protein-focused COVID-19 vaccine strategy due to neutralizing antibody escape and waning antibody-mediated immunity. In contrast, T cell-mediated immunity targeting conserved epitopes may offer broad and long-lasting protection. However, whether T cells alone can provide sufficient protection remains unclear. Here, we identified both Omicron BA.1-specific and ancestral (Wuhan)-conserved CD8 T cell epitopes in the SARS-CoV-2 spike protein and evaluated them as carrier-protein fusion vaccines in mouse models. Subcutaneous immunizations with two CD8 epitope peptides substantially lowered lung viral load and conferred protection against low-dose viral challenge, but not against high-dose challenge. Notably, intranasal boosting-with or without adjuvant-enhanced lung resident memory T cell responses and conferred potent, durable protection against high-dose infection. These findings emphasize the importance of mucosal vaccination to boost protective T cell immunity against SARS-CoV-2 and support the potential of T cell-based vaccines targeting conserved epitopes for broad immunity against SARS-CoV-2 and other respiratory viral threats.","journal":"Science Advances","year":2025,"id":548796,"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":0.9372,"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":1442482,"name":"Thao Nguyen","orcid":"0009-0009-0338-6053","position":1,"is_corresponding":false},{"id":553554,"name":"Lindsay G. A. McKay","orcid":"0000-0003-0369-9067","position":2,"is_corresponding":false},{"id":568156,"name":"Sravya Sowdamini Nakka","orcid":null,"position":3,"is_corresponding":false},{"id":661760,"name":"Pan Hu","orcid":"0000-0003-1887-8885","position":4,"is_corresponding":false},{"id":1442483,"name":"Jana S. McBride","orcid":"0009-0002-7651-7957","position":5,"is_corresponding":false},{"id":895022,"name":"Anthony C. Liang","orcid":"0000-0002-8792-8260","position":6,"is_corresponding":false},{"id":525292,"name":"Rachel M. Olson","orcid":"0000-0002-6973-4331","position":7,"is_corresponding":false},{"id":281386,"name":"James J. Moon","orcid":"0000-0001-8246-931X","position":8,"is_corresponding":false},{"id":256462,"name":"Andrew D. Luster","orcid":"0000-0001-9679-7912","position":9,"is_corresponding":false},{"id":109938,"name":"Anthony Griffiths","orcid":"0000-0001-5435-8364","position":10,"is_corresponding":false},{"id":108430,"name":"Stephen J. Elledge","orcid":"0000-0001-7923-6283","position":11,"is_corresponding":false},{"id":655010,"name":"Genghao Chen","orcid":"0000-0002-8585-9943","position":0,"is_corresponding":true}],"reference_count":63,"raw_metadata":null,"created_at":"2026-07-19T02:54:03.053965Z","pmid":"41270167","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":[]}