Oral immunization of rabbits with enterotoxigenic Escherichia coli protects against intraintestinal challenge.
The development of a successful oral vaccine against enterotoxigenic Escherichia coli depends upon the identification of appropriate protective antigens which can be delivered effectively to intestinal mucosa. We have determined in a modified RITARD model the relative protection against intraintestinal challenge afforded by oral immunization with live enterotoxigenic E. coli carrying different candidate antigens. Studies were done with both wild-type strains and genetically manipulated strains of enterotoxigenic E. coli (parent strain E1392/75 2A) which carried plasmids containing intact heat-labile toxin (LT) gene sequences or various mutations of the LT genes. Immunizations were done by orogastric tube inoculation on days 0, 7, and 14; challenges were done on day 33. Protection against diarrhea with a homologous challenge was found to be 84 to 100% (P less than 0.01). Protection against diarrhea with challenges in which specific antigens could be tested included the following: (i) O and H antigens (O6:H16), 87 to 100% protection with different E. coli strains with identical O and H antigens (P less than 0.01) but no protection against a heterologous challenge; (ii) LT or the B subunit of LT only, approximately 50% protection (P less than 0.02). These findings suggest that O antigens are highly protective in this model but afford only serotype-specific protection and that the B subunit (with or without the A subunit) affords less protection but confers cross-protection against heterologous strains producing LT. This model should be useful in further defining appropriate protective antigens for candidate enterotoxigenic E. coli vaccine strains.
Sack
R B
RB
Department of Medicine, Francis Scott Key Medical Center, Baltimore, Maryland 21224.
Kline
R L
RL
Spira
W M
WM
D000284:Administration, Oral; D000818:Animals; D000942:Antigens, Bacterial / Q000276:immunology; D001427:Bacterial Toxins / Q000276:immunology; D001428:Bacterial Vaccines / Q000008:administration & dosage / Q000276:immunology*; D002473:Cell Wall / Q000276:immunology; D003967:Diarrhea / Q000517:prevention & control*; D004768:Enterotoxins / Q000096:biosynthesis / Q000276:immunology; D004926:Escherichia coli / Q000276:immunology*; D004927:Escherichia coli Infections / Q000517:prevention & control*; D029968:Escherichia coli Proteins; D005260:Female; D007421:Intestine, Small / Q000382:microbiology; D008297:Male; D011817:Rabbits
D000942:Antigens, Bacterial; D001427:Bacterial Toxins; D001428:Bacterial Vaccines; D004768:Enterotoxins; D029968:Escherichia coli Proteins; C027538:heat-labile enterotoxin, E coli