title: Oral Typhoid Vaccination With Live-Attenuated Salmonella Typhi Strain Ty21a Generates Ty21a-Responsive and Heterologous Influenza Virus-Responsive CD4+ and CD8+ T Cells at the Human Intestinal Mucosa.
abstract: BACKGROUND
  Oral vaccination with live-attenuated Salmonella Typhi strain Ty21a is modestly efficacious, but the mechanisms of protection are currently unknown. While humoral and cellular immune responses are well described in peripheral blood, the cellular response at the intestinal mucosa has never been directly assessed.
  
  
  METHODS
  We vaccinated healthy adults with Ty21a and assessed humoral and cellular immunity in vaccinated volunteers and controls after 18 days. Immunoglobulin levels were assessed in peripheral blood by an enzyme-linked immunosorbent assay. Cellular responses were assessed in peripheral blood and at the duodenal and colonic mucosa by flow cytometry.
  
  
  RESULTS
  We demonstrate the generation of Ty21a-responsive and heterologous influenza virus-responsive CD4(+) and CD8(+) T cells at the duodenal mucosa. All duodenal responses were consistently correlated, and no responses were observed at the colonic mucosa. Peripheral anti-lipopolysaccharide immunoglobulin G and immunoglobulin A responses were significantly correlated with duodenal responses. The assessment of integrin β7 expression intensity among peripheral and duodenal T-cell subsets revealed varied capacities for mucosal homing and residence.
  
  
  CONCLUSIONS
  The breadth of duodenal cellular responses was not reflected peripherally. The direct evaluation of mucosal immune defense may yield functional correlates of protection and could provide insight into mechanisms that may be manipulated to enhance vaccine immunogenicity.
authors.affiliation: Department of Clinical Infection, Microbiology, and Immunology, Institute of Infection and Global Health, University of Liverpool Department of Clinical Sciences, Liverpool School of Tropical Medicine.
authors.forename: Shaun H
authors.initials: SH
authors.lastname: Pennington
authors.affiliation: Department of Clinical Infection, Microbiology, and Immunology, Institute of Infection and Global Health, University of Liverpool Department of Clinical Sciences, Liverpool School of Tropical Medicine.
authors.forename: Ameeka L
authors.initials: AL
authors.lastname: Thompson
authors.affiliation: Department of Clinical Sciences, Liverpool School of Tropical Medicine.
authors.forename: Adam K A
authors.initials: AK
authors.lastname: Wright
authors.affiliation: Department of Clinical Sciences, Liverpool School of Tropical Medicine.
authors.forename: Daniela M
authors.initials: DM
authors.lastname: Ferreira
authors.affiliation: Department of Clinical Sciences, Liverpool School of Tropical Medicine.
authors.forename: Kondwani C
authors.initials: KC
authors.lastname: Jambo
authors.affiliation: Department of Clinical Sciences, Liverpool School of Tropical Medicine.
authors.forename: Angela D
authors.initials: AD
authors.lastname: Wright
authors.affiliation: Department of Clinical Sciences, Liverpool School of Tropical Medicine.
authors.forename: Brian
authors.initials: B
authors.lastname: Faragher
authors.affiliation: International AIDS Vaccine Initiative, Human Immunology Laboratory, Imperial College, London, United Kingdom.
authors.forename: Jill W
authors.initials: JW
authors.lastname: Gilmour
authors.affiliation: Department of Clinical Sciences, Liverpool School of Tropical Medicine.
authors.forename: Stephen B
authors.initials: SB
authors.lastname: Gordon
authors.affiliation: Department of Clinical Infection, Microbiology, and Immunology, Institute of Infection and Global Health, University of Liverpool.
authors.forename: Melita A
authors.initials: MA
authors.lastname: Gordon
mesh_terms: D000284:Administration, Oral; D000328:Adult; D000907:Antibodies, Bacterial / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D007111:Immunity, Cellular; D056724:Immunity, Humoral; D000071497:Immunogenicity, Vaccine; D007413:Intestinal Mucosa / Q000276:immunology*; D008297:Male; D009975:Orthomyxoviridae / Q000276:immunology; D011135:Polysaccharides, Bacterial / Q000276:immunology*; D012485:Salmonella typhi / Q000276:immunology*; D014436:Typhoid-Paratyphoid Vaccines / Q000276:immunology*; D014613:Vaccines, Attenuated / Q000276:immunology; D055815:Young Adult
chemical_list: D000907:Antibodies, Bacterial; D011135:Polysaccharides, Bacterial; C072772:Ty21a typhoid vaccine; D014436:Typhoid-Paratyphoid Vaccines; D014613:Vaccines, Attenuated
keywords: Salmonella; T cells; Ty21a; cellular immunity; cytokines; heterologous immunity; humoral immunity; immunoglobulins; typhoid
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