title: Non-replicating oral whole cell vaccine protective against enterotoxigenic Escherichia coli (ETEC) diarrhea: stimulation of anti-CFA (CFA/I) and anti-enterotoxin (anti-LT) intestinal IgA and protection against challenge with ETEC belonging to heterologous serotypes.
abstract: An oral killed (non-replicating) whole-cell anti-ETEC vaccine was prepared by treating enterotoxigenic Escherichia coli strain H-10407 (ST + LT +; 078: H11: CFA/I) with a 100%-lethal amount of colicin E2. Colicin E2 is a potent DNA endonuclease which enters the target bacterial cells without disrupting cellular integrity. Thus the vaccine consists of intact cells lacking chromosomal and plasmid DNA but possessing a normal complement of antigens, including CFA/I and enterotoxin(s), unaltered by chemical- or heat-treatment. Young healthy volunteers were administered two oral doses, one month apart, of approximately 3 x 10(10) vaccine cells. Of 22 vaccinees, 17 (77.3%) showed an intestinal anti-CFA/I IgA response and 19 (86.4%) showed an increase in intestinal anti-LT IgA. Twenty of 22 (90.9%) vaccinees had antibody responses to either CFA/I, LT, or both antigens, demonstrating that colicin E2-treated CFA-positive E. coli cells are an efficient vehicle in terms of delivery of antigens to the gut immune system. We previously demonstrated protection of vaccinees against challenge with the living homologous ETEC (strain H-10407). In this study, two groups of 8 vaccinees were challenged with a diarrheagenic dose of virulent ST + LT + ETEC of heterologous serotype; one group was challenged with a CFA/I-positive 063: H- strain and the other group was challenged with a CFA/II-positive 06: H16 strain. Approximately 75% efficacy was achieved in both challenge groups. None of the 16 vaccinees who had responded to both CFA/I and LT became ill upon challenge while both of the vaccinees who had not responded to either antigen did.(ABSTRACT TRUNCATED AT 250 WORDS)
authors.affiliation: Mucosal Immunity Laboratory, Veterans Administration Medical Center, Houston, Texas 77211.
authors.forename: D G
authors.initials: DG
authors.lastname: Evans
authors.forename: D J
authors.initials: DJ
authors.lastname: Evans
authors.forename: A R
authors.initials: AR
authors.lastname: Opekun
authors.forename: D Y
authors.initials: DY
authors.lastname: Graham
mesh_terms: D000284:Administration, Oral; D000328:Adult; D000942:Antigens, Bacterial / Q000276:immunology; D001427:Bacterial Toxins / Q000276:immunology; D001428:Bacterial Vaccines / Q000008:administration & dosage / Q000627:therapeutic use*; D003967:Diarrhea / Q000517:prevention & control*; D004768:Enterotoxins / Q000276:immunology; D004926:Escherichia coli / Q000145:classification / Q000276:immunology; D004927:Escherichia coli Infections / Q000276:immunology / Q000517:prevention & control*; D029968:Escherichia coli Proteins; D005260:Female; D036781:Fimbriae Proteins; D006801:Humans; D007070:Immunoglobulin A / Q000096:biosynthesis; D007422:Intestines / Q000276:immunology; D008297:Male; D015164:Vaccines, Inactivated / Q000008:administration & dosage / Q000627:therapeutic use
chemical_list: D000942:Antigens, Bacterial; D001427:Bacterial Toxins; D001428:Bacterial Vaccines; D004768:Enterotoxins; D029968:Escherichia coli Proteins; D007070:Immunoglobulin A; D015164:Vaccines, Inactivated; C022924:colonization factor antigens; D036781:Fimbriae Proteins; C027538:heat-labile enterotoxin, E coli