Safety and immunogenicity of live recombinant Salmonella enterica serovar Typhi Ty21a expressing urease A and B from Helicobacter pylori in human volunteers.
Helicobacter pylori urease was expressed in the common live typhoid vaccine Ty21a yielding Ty21a(pDB1). Nine volunteers received Ty21a(pDB1) and three control volunteers received Ty21a. No serious adverse effects were observed in any of the volunteers. Ten out of 12 volunteers developed humoral immune responses to the Salmonella carrier as detected by antigen-specific antibody-secreting cells but only two volunteers seroconverted. A total of five volunteers showed responses in one or two out of three assays for cellular responses to the carrier (proliferation, IFN-gamma-secretion, IFN-gamma-ELISPOT). Three of the volunteers that had received Ty21a(pDB1) showed a weak but significant T-cell response to Helicobacter urease, while no volunteer had detectable humoral responses to urease. Ty21a(pDB1) is a suitable prototype to optimize Salmonella-based vaccination for efficient cellular responses that could mediate protective immunity against Helicobacter.
Bumann
D
D
Max-Planck-Institut für Infektionsbiologie, Abteilung Molekulare Biologie, Schumannstrasse 21/22, D-10117 Berlin, Germany.
Metzger
W G
WG
Mansouri
E
E
Palme
O
O
Wendland
M
M
Hurwitz
R
R
Haas
G
G
Aebischer
T
T
von Specht
B U
BU
Meyer
T F
TF
D000293:Adolescent; D000328:Adult; D000907:Antibodies, Bacterial / Q000096:biosynthesis; D000942:Antigens, Bacterial / Q000235:genetics; D001402:B-Lymphocytes / Q000276:immunology; D001428:Bacterial Vaccines / Q000009:adverse effects / Q000235:genetics / Q000276:immunology / Q000494:pharmacology*; D004311:Double-Blind Method; D005260:Female; D015870:Gene Expression; D016480:Helicobacter pylori / Q000201:enzymology* / Q000235:genetics / Q000276:immunology*; D006801:Humans; D007371:Interferon-gamma / Q000096:biosynthesis; D008213:Lymphocyte Activation; D008297:Male; D012449:Safety; D012485:Salmonella typhi / Q000235:genetics*; D013601:T-Lymphocytes / Q000276:immunology; D014510:Urease / Q000235:genetics* / Q000276:immunology*; D014614:Vaccines, Synthetic / Q000009:adverse effects / Q000235:genetics / Q000276:immunology / Q000494:pharmacology
D000907:Antibodies, Bacterial; D000942:Antigens, Bacterial; D001428:Bacterial Vaccines; D014614:Vaccines, Synthetic; D007371:Interferon-gamma; D014510:Urease