title: Shigella antigen-specific B memory cells are associated with decreased disease severity in subjects challenged with wild-type Shigella flexneri 2a.
abstract: The role of Shigella-specific B memory (BM) in protection has not been evaluated in human challenge studies. We utilized cryopreserved pre- and post-challenge peripheral blood mononuclear cells and sera from wild-type Shigella flexneri 2a (wt-2457T) challenges. Challenged volunteers were either naïve or subjects who had previously ingested wt-2457T or been immunized with hybrid Escherichia coli-Shigella live oral candidate vaccine (EcSf2a-2). BM and antibody titers were measured against lipopolysaccharide (LPS) and recombinant invasion plasmid antigen B (IpaB); results were correlated with disease severity following challenge. Pre-challenge IgA IpaB-BM and post-challenge IgA LPS-BM in the previously exposed subjects negatively correlated with disease severity upon challenge. Similar results were observed with pre-challenge IgG anti-LPS and anti-IpaB titers in vaccinated volunteers. Inverse correlations between magnitude of pre-challenge IgG antibodies to LPS and IpaB, as well as IgA IpaB-BM and post-challenge IgA LPS-BM with disease severity suggest a role for antigen-specific BM in protection.
authors: Center for Vaccine Development, Department of Pediatrics, University of Maryland School of Medicine, Baltimore, MD, USA.
authors: Rezwanul
authors: R
authors: Wahid
authors: Jakub K
authors: JK
authors: Simon
authors: Wendy L
authors: WL
authors: Picking
authors: Karen L
authors: KL
authors: Kotloff
authors: Myron M
authors: MM
authors: Levine
authors: Marcelo B
authors: MB
authors: Sztein
mesh_terms: D000907:Antibodies, Bacterial / Q000097:blood / Q000276:immunology; D000942:Antigens, Bacterial / Q000276:immunology*; D001402:B-Lymphocytes / Q000276:immunology* / Q000382:microbiology; D001426:Bacterial Proteins / Q000276:immunology; D016022:Case-Control Studies; D004405:Dysentery, Bacillary / Q000097:blood / Q000276:immunology* / Q000382:microbiology / Q000517:prevention & control; D000939:Epitopes; D006801:Humans; D007156:Immunologic Memory / Q000276:immunology*; D007963:Leukocytes, Mononuclear / Q000276:immunology; D008070:Lipopolysaccharides / Q000276:immunology; D012189:Retrospective Studies; D022281:Shigella Vaccines / Q000008:administration & dosage*; D012763:Shigella flexneri / Q000166:cytology / Q000276:immunology*; D018709:Statistics, Nonparametric
chemical_list: D000907:Antibodies, Bacterial; D000942:Antigens, Bacterial; D001426:Bacterial Proteins; D000939:Epitopes; D008070:Lipopolysaccharides; D022281:Shigella Vaccines; C087447:ipaB protein, Shigella
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