{"doi":"10.3389/fimmu.2020.574057","title":"Vi-Vaccinations Induce Heterogeneous Plasma Cell Responses That Associate With Protection From Typhoid Fever","abstract":"Vi-polysaccharide conjugate vaccines are efficacious against cases of typhoid fever; however, an absolute correlate of protection is not established. In this study, we investigated the leukocyte response to a Vi-tetanus toxoid conjugate vaccine (Vi-TT) in comparison with a plain polysaccharide vaccine (Vi-PS) in healthy adults subsequently challenged with Salmonella Typhi. Immunological responses and their association with challenge outcome was assessed by mass cytometry and Vi-ELISpot assay. Immunization induced significant expansion of plasma cells in both vaccines with modest T follicular helper cell responses detectable after Vi-TT only. The Vi-specific IgG and IgM B cell response was considerably greater in magnitude in Vi-TT recipients. Intriguingly, a significant increase in a subset of IgA + plasma cells expressing mucosal migratory markers α4β7 and CCR10 was observed in both vaccine groups, suggesting a gut-tropic, mucosal response is induced by Vi-vaccination. The total plasma cell response was significantly associated with protection against typhoid fever in Vi-TT vaccinees but not Vi-PS. IgA + plasma cells were not significantly associated with protection for either vaccine, although a trend is seen for Vi-PS. Conversely, the IgA - fraction of the plasma cell response was only associated with protection in Vi-TT. In summary, these data indicate that a phenotypically heterogeneous response including both gut-homing and systemic antibody secreting cells may be critical for protection induced by Vi-TT vaccination.","journal":"Frontiers in Immunology","year":2020,"id":81614,"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":14,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9532,"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":423075,"name":"Marije K. Verheul","orcid":null,"position":1,"is_corresponding":false},{"id":421987,"name":"Michael D. Leipold","orcid":"0000-0001-5389-0906","position":2,"is_corresponding":false},{"id":421988,"name":"Gerlinde Obermoser","orcid":"0000-0003-4349-5149","position":3,"is_corresponding":false},{"id":300912,"name":"Celina Jin","orcid":"0000-0002-7614-8787","position":4,"is_corresponding":false},{"id":300916,"name":"Elizabeth Jones","orcid":"0000-0001-5821-1001","position":5,"is_corresponding":false},{"id":421989,"name":"Joshua S Starr","orcid":"0000-0003-2449-1601","position":6,"is_corresponding":false},{"id":421990,"name":"Irina Mohorianu","orcid":"0000-0003-4863-761X","position":7,"is_corresponding":false},{"id":421991,"name":"Christoph J. Blohmke","orcid":"0000-0002-1453-9651","position":8,"is_corresponding":false},{"id":3342,"name":"Holden T. Maecker","orcid":"0000-0003-0795-9946","position":9,"is_corresponding":false},{"id":106100,"name":"Giorgio Napolitani","orcid":"0000-0002-3605-6394","position":10,"is_corresponding":false},{"id":300913,"name":"Jennifer Hill","orcid":"0000-0001-6205-7764","position":11,"is_corresponding":false},{"id":78476,"name":"Andrew J. Pollard","orcid":"0000-0001-7361-719X","position":12,"is_corresponding":false},{"id":423074,"name":"Deborah L Cross","orcid":null,"position":0,"is_corresponding":true}],"reference_count":55,"raw_metadata":null,"created_at":"2026-07-18T21:52:58.921847Z","pmid":"33424833","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":[]}