{"doi":"10.1101/2025.09.15.25335795","title":"A phase 1 randomized, placebo-controlled trial of a combination typhoid and non-typhoidal <i>Salmonella</i> polysaccharide conjugate vaccine","abstract":"Conjugate Vaccine (TSCV) consists of Vi capsule polysaccharide conjugated to tetanus toxoid and core-plus-O-polysaccharides from the two most prevalent invasive non-typhoidal serovars (Typhimurium, Enteritidis) conjugated to serovar-homologous flagellin subunits. We conducted a first-in-human, randomized, placebo-controlled, stepwise-dose-escalation phase 1 trial (NCT03981952) evaluating TSCV safety and immunogenicity; 22 healthy adults aged 18-45 years were randomly allocated 6.25 μg TSCV (n=8), 12.5 μg TSCV (n=10), or placebo (n=4). TSCV was safe and well-tolerated, with the most common solicited symptom being short-lived injection site pain. For each of the 3 polysaccharides, serum IgG and IgA ELISA antibody responses, as demonstrated by four-fold or greater increases over baseline, were observed among all vaccinees but among no placebo recipients. Binding and functional antibodies, gut-homing antibody secreting cells, and polysaccharide-specific memory B cells responses were also elicited. ClinicalTrials.gov Registry NCT03981952.","journal":"medRxiv","year":2025,"id":575246,"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":0.9185,"is_data_producer":true,"deposit_databanks":{"ClinicalTrials.gov":["NCT03981952"]},"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":503768,"name":"Robin S. Barnes","orcid":null,"position":1,"is_corresponding":false},{"id":536441,"name":"Michael J. Sikorski","orcid":"0000-0002-3811-7285","position":2,"is_corresponding":false},{"id":1092521,"name":"Reva Datar","orcid":"0000-0002-1968-2086","position":3,"is_corresponding":false},{"id":1483554,"name":"Roohali Sukhavasi","orcid":null,"position":4,"is_corresponding":false},{"id":760803,"name":"Yuanyuan Liang","orcid":"0000-0003-0360-286X","position":5,"is_corresponding":false},{"id":528542,"name":"Rekha R. Rapaka","orcid":"0000-0002-4770-4422","position":6,"is_corresponding":false},{"id":299790,"name":"Marcela F. Pasetti","orcid":"0000-0003-0894-4009","position":7,"is_corresponding":false},{"id":317430,"name":"Marcelo B. Sztein","orcid":"0000-0001-8282-860X","position":8,"is_corresponding":false},{"id":528543,"name":"Rezwanul Wahid","orcid":"0000-0002-5623-1903","position":9,"is_corresponding":false},{"id":260735,"name":"Sharon M. Tennant","orcid":"0000-0002-0651-5748","position":10,"is_corresponding":false},{"id":742246,"name":"Raphael Simon","orcid":"0000-0002-4136-0948","position":11,"is_corresponding":false},{"id":765384,"name":"Scott M. Baliban","orcid":"0000-0002-2771-1609","position":12,"is_corresponding":false},{"id":715599,"name":"James E. Galen","orcid":"0000-0003-4202-0213","position":13,"is_corresponding":false},{"id":395418,"name":"Andrew Lees","orcid":"0000-0002-8370-4876","position":14,"is_corresponding":false},{"id":620513,"name":"Biana Bernshtein","orcid":"0000-0002-7957-2575","position":15,"is_corresponding":false},{"id":805827,"name":"Galit Alter","orcid":"0000-0002-9221-6735","position":16,"is_corresponding":false},{"id":1483207,"name":"Raches Ella","orcid":"0000-0002-4646-4471","position":17,"is_corresponding":false},{"id":1483208,"name":"K. S. Mohan","orcid":"0000-0001-6407-7654","position":18,"is_corresponding":false},{"id":1483555,"name":"Madhulika Naidu","orcid":null,"position":19,"is_corresponding":false},{"id":226249,"name":"Deepak A. Rao","orcid":"0000-0001-9672-7746","position":20,"is_corresponding":false},{"id":1296225,"name":"Krishna M. Ella","orcid":"0000-0002-0021-5082","position":21,"is_corresponding":false},{"id":299789,"name":"Myron M. Levine","orcid":"0000-0002-5721-5040","position":22,"is_corresponding":false},{"id":415859,"name":"Wilbur H. Chen","orcid":"0000-0001-7741-5536","position":0,"is_corresponding":true}],"reference_count":32,"raw_metadata":null,"created_at":"2026-07-19T02:57:48.486077Z","pmid":"41001453","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":[]}