A completely synthetic toxoid vaccine containing Escherichia coli heat-stable toxin and antigenic determinants of the heat-labile toxin B subunit.
The immunodeterminant regions of the Escherichia coli heat-labile toxin B subunit were identified by determining the antigenicity, by using enzyme-linked immunosorbent assays, of synthetically produced peptides corresponding to various segments of its 124-amino-acid sequence. The addition of the 18-amino-acid sequence of heat-stable toxin (ST) to some of these peptides enhanced their B subunit antigenicity. Peptide residues containing the 26 amino acids of B subunit sequence 58 to 83 joined to the 18-amino-acid sequence of ST yielded a 44-amino-acid peptide whose antigenicity was 50% that of both native B subunit and ST. This peptide was completely nontoxic when tested in Chinese hamster ovary tissue culture, suckling mouse, and rat ligated ileal loop assays. Peroral immunization of rats with the polymeric form of this peptide yielded a dose-dependent response of intestinal immunoglobulin A antitoxin titers to both the ST and B subunit components and provided strong protection against challenge with viable ST- and heat-labile toxin-producing E. coli strains. The immunogenicity of the synthetic peptide in rats was the same as that of ST and about 50% that of native B subunit. The completely synthetic peptide vaccine has the following advantages over previously described toxoid vaccines that consist of synthetic ST chemically cross-linked to native B subunit derived from bacterial cultures: it is produced by a single synthetic process, it is completely nontoxic, and it is immunogenic for both ST and B subunit.
Houghten
R A
RA
Engert
R F
RF
Ostresh
J M
JM
Hoffman
S R
SR
Klipstein
F A
FA
D000595:Amino Acid Sequence; D000818:Animals; D001427:Bacterial Toxins / Q000276:immunology*; D001428:Bacterial Vaccines / Q000276:immunology* / Q000633:toxicity; D006224:Cricetinae; D003412:Cricetulus; D004768:Enterotoxins / Q000276:immunology*; D000939:Epitopes / Q000032:analysis*; D029968:Escherichia coli Proteins; D007114:Immunization; D014121:Toxoids / Q000276:immunology* / Q000633:toxicity
D001427:Bacterial Toxins; D001428:Bacterial Vaccines; D004768:Enterotoxins; D000939:Epitopes; D029968:Escherichia coli Proteins; D014121:Toxoids; C034151:heat stable toxin (E coli); C027538:heat-labile enterotoxin, E coli