{"doi":"10.1101/2025.10.31.685426","title":"The ID93 + GLA-3M-052-LS vaccine candidate elicits mucosal and systemic immunogenicity and protective efficacy against <i>Mycobacterium tuberculosis</i> challenge in BCG-primed Collaborative Cross inbred mice","abstract":"ABSTRACT New vaccine approaches are needed against tuberculosis (TB). We sought to optimize mucosal immunogenicity and protective efficacy by modulating the adjuvant component and route of immunization of a next-generation TB vaccine using the recombinant TB vaccine antigen (Ag) ID93. ID93-specific mucosal and systemic immunogenicity and protective efficacy were assessed in the Collaborative Cross 004 mouse strain, a mouse strain susceptible to Mycobacterium tuberculosis ( Mtb ) infection, as a suitable model of Mtb susceptible populations. Immunogenicity data from various vaccine candidates were used to select lead vaccine candidates with the most preferred immunostimulatory profiles using a pre-determined desirability index. A liposomal adjuvant system containing synthetic TLR4 and TLR7/8 ligands (GLA-3M-052-LS), administered by a heterologous intramuscular-intranasal regimen, induced an optimal comprehensive immune response profile including high levels of mucosal antibody and Th1 CD4 + T cells in the lungs. In BCG-primed mice, immunization with intramuscular followed by intranasal ID93 + GLA-3M-052-LS boosts significantly reduced Mtb burden in the lungs after challenge vs. BCG vaccinated mice alone. Thus, ID93 + GLA-3M-052-LS represents a promising next-generation TB vaccine candidate suitable for testing in additional preclinical models.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2025,"id":559422,"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":0.9593,"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":1171173,"name":"Anas Alsharaydeh","orcid":null,"position":1,"is_corresponding":false},{"id":336734,"name":"Darshan N. Kasal","orcid":"0000-0003-2718-7971","position":2,"is_corresponding":false},{"id":554022,"name":"Madeleine F. Jennewein","orcid":"0000-0001-6633-7413","position":3,"is_corresponding":false},{"id":1457671,"name":"Devin S. Brandt","orcid":null,"position":4,"is_corresponding":false},{"id":744375,"name":"Susan Lin","orcid":"0000-0003-4743-3180","position":5,"is_corresponding":false},{"id":985467,"name":"Jasneet Singh","orcid":"0000-0001-6494-7816","position":6,"is_corresponding":false},{"id":986022,"name":"Julie Bakken","orcid":null,"position":7,"is_corresponding":false},{"id":986023,"name":"Raodoh Mohamath","orcid":null,"position":8,"is_corresponding":false},{"id":1453187,"name":"Pauline Fusco","orcid":null,"position":9,"is_corresponding":false},{"id":245288,"name":"Jordi B. Torrelles","orcid":"0000-0001-7702-5941","position":10,"is_corresponding":false},{"id":283984,"name":"Gillian Beamer","orcid":"0000-0001-6782-4424","position":11,"is_corresponding":false},{"id":258353,"name":"Christopher B. Fox","orcid":"0000-0002-4644-2619","position":12,"is_corresponding":false},{"id":495328,"name":"Emily A. Voigt","orcid":"0000-0001-5177-4063","position":0,"is_corresponding":true}],"reference_count":30,"raw_metadata":null,"created_at":"2026-07-19T02:55:34.849815Z","pmid":"41279251","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":[]}