Ability of SPI2 mutant of S. typhi to effectively induce antibody responses to the mucosal antigen enterotoxigenic E. coli heat labile toxin B subunit after oral delivery to humans.
We have evaluated an oral vaccine based on an Salmonella enteric serovar typhi (S. typhi) Ty2 derivative TSB7 harboring deletion mutations in ssaV (SPI-2) and aroC together with a chromosomally integrated copy of eltB encoding the B subunit of enterotoxigenic Escherichia coli heat labile toxin (LT-B) in volunteers. Two oral doses of 10(8) or 10(9)CFU were administered to two groups of volunteers and both doses were well tolerated, with no vaccinemia, and only transient stool shedding. Immune responses to LT-B and S. typhi lipopolysaccharide were demonstrated in 67 and 97% of subjects, respectively, without evidence of anti-carrier immunity preventing boosting of LT-B responses in many cases. Further development of this salmonella-based (spi-VEC) system for oral delivery of heterologous antigens appears warranted.
Khan
S
S
Microscience, Wokingham Berkshire RG41 5TU, UK.
Chatfield
S
S
Stratford
R
R
Bedwell
J
J
Bentley
M
M
Sulsh
S
S
Giemza
R
R
Smith
S
S
Bongard
E
E
Cosgrove
C A
CA
Johnson
J
J
Dougan
G
G
Griffin
G E
GE
Makin
J
J
Lewis
D J M
DJ
D000284:Administration, Oral; D000293:Adolescent; D000328:Adult; D000907:Antibodies, Bacterial / Q000097:blood; D000992:Antitoxins / Q000097:blood; D001427:Bacterial Toxins / Q000235:genetics / Q000276:immunology*; D001428:Bacterial Vaccines / Q000235:genetics / Q000276:immunology*; D001769:Blood / Q000382:microbiology; D004768:Enterotoxins / Q000235:genetics / Q000276:immunology*; D004797:Enzyme-Linked Immunosorbent Assay; D004926:Escherichia coli / Q000276:immunology*; D029968:Escherichia coli Proteins / Q000235:genetics / Q000276:immunology*; D005243:Feces / Q000382:microbiology; D006801:Humans; D007074:Immunoglobulin G / Q000097:blood; D008214:Lymphocytes / Q000276:immunology; D008875:Middle Aged; D021122:Protein Subunits / Q000235:genetics / Q000276:immunology*; D012485:Salmonella typhi / Q000235:genetics / Q000276:immunology* / Q000302:isolation & purification; D014613:Vaccines, Attenuated / Q000235:genetics / Q000276:immunology
D000907:Antibodies, Bacterial; D000992:Antitoxins; D001427:Bacterial Toxins; D001428:Bacterial Vaccines; D004768:Enterotoxins; D029968:Escherichia coli Proteins; D007074:Immunoglobulin G; D021122:Protein Subunits; D014613:Vaccines, Attenuated; C027538:heat-labile enterotoxin, E coli