{"doi":"10.1101/2020.11.25.398651","title":"Mucosal vaccination with cyclic-di-nucleotide adjuvants induces effective T cell homing and IL-17 dependent protection against <i>M. tuberculosis</i> infection","abstract":"Abstract The only licensed vaccine for tuberculosis, Mycobacterium bovis Bacille Calmette-Guérin (BCG), is not reliably effective against adult pulmonary tuberculosis. A major hurdle to tuberculosis vaccine development is incomplete understanding of successful immunity against the causative agent Mycobacterium tuberculosis . Recently, we demonstrated that a protein subunit vaccine adjuvanted with STING-activating cyclic-di-nucleotides (CDNs) robustly protects against tuberculosis infection in mice. Here we show mucosal vaccination with this vaccine induces production of T cells that home to lung parenchyma and penetrate lesions in the lung. Protection is partially dependent on IL-17, type I interferon (IFN), and IFN-γ, while the transcription factor STAT-6 is dispensable. Single cell transcriptomics reveals mucosal vaccination with a CDN vaccine increases transcriptional heterogeneity in CD4 cells, including a significant population of non-classical IFN-γ and IL-17 co-expressing Th1-Th17 cells, as well as markers of memory and activation. Th1-Th17 cells in vaccinated mice are enriched for expression of the T cell functional markers Tnfsf8 and Il1r1 relative to more conventional Th1 cells. These data provide critical insight into the immune mediators and diversity of T cell responses that can contribute to vaccine efficacy against M. tuberculosis infection.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2020,"id":131748,"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":0.952,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2020-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":554003,"name":"Erik Van Dis","orcid":"0000-0003-4773-379X","position":1,"is_corresponding":false},{"id":552210,"name":"Xammy Nguyenla","orcid":"0000-0002-7532-8356","position":2,"is_corresponding":false},{"id":585944,"name":"Alexander Baltodano","orcid":"0009-0005-2509-081X","position":3,"is_corresponding":false},{"id":400679,"name":"Gabrielle Pastenkos","orcid":"0000-0002-5958-7542","position":4,"is_corresponding":false},{"id":49002,"name":"Chenling Xu","orcid":"0000-0001-9610-7627","position":5,"is_corresponding":false},{"id":858,"name":"Nir Yosef","orcid":"0000-0001-9004-1225","position":6,"is_corresponding":false},{"id":585945,"name":"Sarah M. McWhirter","orcid":"0000-0002-0460-8537","position":7,"is_corresponding":false},{"id":552211,"name":"Sarah A. Stanley","orcid":"0000-0002-4182-9048","position":8,"is_corresponding":false},{"id":585943,"name":"Robyn M. Jong","orcid":"0000-0002-6289-261X","position":0,"is_corresponding":true}],"reference_count":51,"raw_metadata":null,"created_at":"2026-07-18T23:16:03.875886Z","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":[]}