title: Immunization with Ty21a live oral typhoid vaccine elicits crossreactive multifunctional CD8+ T-cell responses against Salmonella enterica serovar Typhi, S. Paratyphi A, and S. Paratyphi B in humans.
abstract: Previously we have extensively characterized Salmonella enterica serovar Typhi (S. Typhi)-specific cell-mediated immune (CMI) responses in volunteers orally immunized with the licensed Ty21a typhoid vaccine. In this study we measured Salmonella-specific multifunctional (MF) CD8+ T-cell responses to further investigate whether Ty21a elicits crossreactive CMI against S. Paratyphi A and S. Paratyphi B that also cause enteric fever. Ty21a-elicited crossreactive CMI responses against all three Salmonella serotypes were predominantly observed in CD8+ T effector/memory (T(EM)) and, to a lesser extent, in CD8+CD45RA+ T(EM) (T(EMRA)) subsets. These CD8+ T-cell responses were largely mediated by MF cells coproducing interferon-γ and macrophage inflammatory protein-1β and expressing CD107a with or without tumor necrosis factor-α. Significant proportions of Salmonella-specific MF cells expressed the gut-homing molecule integrin α4β7. In most subjects, similar MF responses were observed to S. Typhi and S. Paratyphi B, but not to S. Paratyphi A. These results suggest that Ty21a elicits MF CMI responses against Salmonella that could be critical in clearing the infection. Moreover, because S. Paratyphi A is a major public concern and Ty21a was shown in field studies not to afford cross-protection to S. Paratyphi A, these results will be important in developing a S. Typhi/S. Paratyphi A bivalent vaccine against enteric fevers.
authors: Department of Pediatrics, Center for Vaccine Development, University of Maryland School of Medicine, Baltimore, Maryland, USA.
authors: R
authors: R
authors: Wahid
authors: Department of Pediatrics, Center for Vaccine Development, University of Maryland School of Medicine, Baltimore, Maryland, USA.
authors: S
authors: S
authors: Fresnay
authors: Department of Pediatrics, Center for Vaccine Development, University of Maryland School of Medicine, Baltimore, Maryland, USA.|Department of Medicine, Center for Vaccine Development, University of Maryland School of Medicine, Baltimore, Maryland, USA.
authors: M M
authors: MM
authors: Levine
authors: Department of Pediatrics, Center for Vaccine Development, University of Maryland School of Medicine, Baltimore, Maryland, USA.|Department of Medicine, Center for Vaccine Development, University of Maryland School of Medicine, Baltimore, Maryland, USA.
authors: M B
authors: MB
authors: Sztein
mesh_terms: D000328:Adult; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D003429:Cross Reactions / Q000276:immunology; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D008297:Male; D008875:Middle Aged; D010284:Paratyphoid Fever / Q000276:immunology / Q000517:prevention & control*; D011135:Polysaccharides, Bacterial / Q000276:immunology*; D012482:Salmonella paratyphi A / Q000276:immunology; D012484:Salmonella paratyphi B / Q000276:immunology; D012485:Salmonella typhi / Q000276:immunology; D014435:Typhoid Fever / Q000276:immunology / Q000517:prevention & control*; D014436:Typhoid-Paratyphoid Vaccines / Q000276:immunology*; D055815:Young Adult
chemical_list: D011135:Polysaccharides, Bacterial; C072772:Ty21a typhoid vaccine; D014436:Typhoid-Paratyphoid Vaccines