{"doi":"10.1093/jimmun/vkaf283.451","title":"Identification of TLR-based adjuvants suitable for polysaccharide antigen vaccines in humans 2545","abstract":"Abstract Description The TLR4 agonist, monophosphoryl lipid A, significantly increases antibody (Ab) responses to T cell independent type 2 antigens (TI-2) in mice in a manner dependent on B cell-intrinsic TLR4 expression and MyD88 signaling. Given the poor responsiveness of human B cells to TLR4 agonists, we sought to identify alternative MyD88-activating TLR agonists that could potentially function as suitable adjuvants to enhance humoral responses to polysaccharide antigens in humans. We activated human PBMC and purified B cells with TLR agonists, strong B cell receptor crosslinking, or both and assessed activation and Ab secretion in vitro. Agonists that augmented Ab secretion in conjunction with BCR crosslinking over that achieved with either stimulation alone were further tested in mice. Pam3Csk4, a TLR1/2 agonist, in combination with squalene, significantly increased primary and secondary IgM and IgG responses to pneumococcal polysaccharide (PPS) and provided increased protection against pneumococcal infection in wild type mice. Furthermore, Pam3Csk4-squalene significantly increased the production of PPS-specific Abs in huPBMC-reconstituted NSG mice and these Abs provided significantly increased protection in a lethal pneumococcal challenge model. Collectively, this work reveals the promise TLR1/2 agonists as adjuvants for polysaccharide vaccines in humans. Funding Sources Supported by NIH/NIAID 5R21AI144758-02 and 5T32AI007401-28 Topic Categories Vaccines and Immunotherapy (VAC)","journal":"The Journal of Immunology","year":2025,"id":586117,"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":0.9576,"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":1500500,"name":"Jamie Jennings-Gee","orcid":null,"position":1,"is_corresponding":false},{"id":1500501,"name":"Karen M Haas","orcid":null,"position":2,"is_corresponding":false},{"id":1500499,"name":"Alexis Elizabeth Morse","orcid":null,"position":0,"is_corresponding":true}],"reference_count":0,"raw_metadata":null,"created_at":"2026-07-19T02:59:28.666390Z","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":[]}