Epitope maps of the Escherichia coli heat-labile toxin B subunit for development of a synthetic oral vaccine.
Linear B- and T-cell epitopes spanning all 103 amino acids of the Escherichia coli heat-labile toxin B subunit (LT-B) were assessed in mice orally immunized with native LT or with recombinant Salmonella enteritidis expressing LT-B. Oral administration of native LT induced mucosal immunoglobulin A (IgA) antibodies reactive with an epitope at residues 85 to 91, while IgA induced by recombinant Salmonella LT-B reacted with an epitope at residues 36 to 44. Serum IgG anti-LT-B antibodies from mice orally immunized with either LT or with recombinant Salmonella LT-B were directed to both epitopes. A single T-cell epitope spanning residues 34 to 42 was identified by T-cell proliferative and cytokine responses. When a 20-mer peptide (residues 26 to 45) with B- and T-cell epitopes was given orally to BALB/c (H-2(d)) and B10 congenic (I-A(d), I-A(b), and I-A(k)) mice, significant fecal IgA and serum IgG anti-LT-B antibodies were induced. The peptide also induced LT-B-specific T-cell proliferative responses in these mice. Orally administered LT-B peptide (residues 26 to 45) induced a cytokine profile indicative of both T helper 1- and 2-type cells. The remarkable immunogenicity of this 20-mer peptide makes it a candidate for a vaccine to protect against enterotoxigenic E. coli.
Takahashi
I
I
Departments of Microbiology and Oral Biology, University of Alabama at Birmingham Medical Center, 35294, USA.
Kiyono
H
H
Jackson
R J
RJ
Fujihashi
K
K
Staats
H F
HF
Hamada
S
S
Clements
J D
JD
Bost
K L
KL
McGhee
J R
JR
D000284:Administration, Oral; D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology; D001427:Bacterial Toxins / Q000276:immunology*; D016207:Cytokines / Q000096:biosynthesis; D004768:Enterotoxins / Q000276:immunology*; D018604:Epitope Mapping; D004926:Escherichia coli / Q000276:immunology*; D029968:Escherichia coli Proteins; D005677:G(M1) Ganglioside / Q000378:metabolism; D007071:Immunoglobulin A, Secretory / Q000096:biosynthesis; D007074:Immunoglobulin G / Q000097:blood; D007132:Immunoglobulin Isotypes / Q000097:blood; D051379:Mice; D008807:Mice, Inbred BALB C; D010446:Peptide Fragments / Q000378:metabolism; D014614:Vaccines, Synthetic / Q000276:immunology*
D001427:Bacterial Toxins; D016207:Cytokines; D004768:Enterotoxins; D029968:Escherichia coli Proteins; D007071:Immunoglobulin A, Secretory; D007074:Immunoglobulin G; D007132:Immunoglobulin Isotypes; D010446:Peptide Fragments; D014614:Vaccines, Synthetic; D005677:G(M1) Ganglioside; C027538:heat-labile enterotoxin, E coli