title: Concomitant induction of CD4+ and CD8+ T cell responses in volunteers immunized with Salmonella enterica serovar typhi strain CVD 908-htrA.
abstract: Type 1 cell-mediated immunity might play an important role in protection from typhoid fever. We evaluated whether immunization with Salmonella enterica serovar Typhi (S. Typhi) strain CVD 908-htrA (a Delta aroC Delta aroD Delta htrA mutant), a leading live oral typhoid vaccine candidate, elicits specific CD4(+) and CD8(+) S. Typhi immune responses. Potent CTL responses and IFN-gamma secretion by CD8(+) T cells were detected following immunization with CVD 908-htrA in high (4.5 x 10(8) CFU) and low (5 x 10(7) CFU) dosages. S. Typhi-specific CTL were observed in six of eight vaccinees (four high and two low dose) after immunization. Mean increases in the frequency of IFN-gamma spot-forming cells (SFC) in the presence of S. Typhi-infected targets were 221 +/- 41 SFC/10(6) PBMC and 233 +/- 87 SFC/10(6) PBMC, in the high and low dose groups, respectively. Strong CD4(+) T cell responses were also observed. Increases in the IFN-gamma production to soluble S. Typhi flagella (STF) occurred in 82 and 38% of the volunteers who received the high and low doses, respectively. Robust correlations were observed between volunteers that responded with IFN-gamma SFC to stimulation with S. Typhi-infected cells and IFN-gamma released in response to stimulation with STF Ags (r = 0.822, p < 0.001) and between CTL and IFN-gamma production to STF (r = 0.818, p = 0.013). These data demonstrating the concomitant induction of both CD4- and CD8-mediated CMI are consistent with a significant role for type 1 immunity in controlling typhoid infection and support the continuing evaluation of CVD 908-htrA as a typhoid vaccine candidate.
authors.affiliation: Center for Vaccine Development, University of Maryland School of Medicine, Baltimore, MD 21201, USA.
authors.forename: Rosângela
authors.initials: R
authors.lastname: Salerno-Gonçalves
authors.forename: Timothy L
authors.initials: TL
authors.lastname: Wyant
authors.forename: Marcela F
authors.initials: MF
authors.lastname: Pasetti
authors.forename: Marcelo
authors.initials: M
authors.lastname: Fernandez-Viña
authors.forename: Carol O
authors.initials: CO
authors.lastname: Tacket
authors.forename: Myron M
authors.initials: MM
authors.lastname: Levine
authors.forename: Marcelo B
authors.initials: MB
authors.lastname: Sztein
mesh_terms: D000284:Administration, Oral; D000293:Adolescent; D000328:Adult; D000907:Antibodies, Bacterial / Q000096:biosynthesis / Q000097:blood; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism / Q000382:microbiology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism / Q000382:microbiology; D018592:Cross-Over Studies; D003601:Cytotoxicity Tests, Immunologic; D004311:Double-Blind Method; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006360:Heat-Shock Proteins / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology*; D006801:Humans; D007371:Interferon-gamma / Q000378:metabolism; D008070:Lipopolysaccharides / Q000276:immunology; D008213:Lymphocyte Activation / Q000276:immunology*; D008297:Male; D033903:Periplasmic Proteins / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology*; D012485:Salmonella typhi / Q000235:genetics / Q000276:immunology*; D012697:Serine Endopeptidases / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology / Q000378:metabolism / Q000382:microbiology; D014436:Typhoid-Paratyphoid Vaccines / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology*; D014613:Vaccines, Attenuated / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology
chemical_list: D000907:Antibodies, Bacterial; D006360:Heat-Shock Proteins; D008070:Lipopolysaccharides; D033903:Periplasmic Proteins; D014436:Typhoid-Paratyphoid Vaccines; D014613:Vaccines, Attenuated; D007371:Interferon-gamma; C061682:DegP protease; D012697:Serine Endopeptidases