title: Immunoprotective oral whole cell vaccine for enterotoxigenic Escherichia coli diarrhea prepared by in situ destruction of chromosomal and plasmid DNA with colicin E2.
abstract: Vaccine regimens which mimic actual infection with bacterial enteropathogens should offer the best opportunity for successful long-term immunoprotection against diarrheal disease caused by enterotoxigenic Escherichia coli (ETEC) or Vibrio cholerae. Based on this principle, we designed and tested an oral whole cell anti-ETEC vaccine consisting of intact cells of ETEC strain H-10407 (ST+LT+; O78:H11:CFA/I) which were rendered incapable of replication by treatment with a potent DNA endonuclease, colicin E2. Young healthy volunteers were administered two oral doses of either placebo or approx. 3 X 10(10) vaccine cells. In a double-blind study, 9 of 10 vaccinees responded with an increase in CFA/I-specific intestinal IgA antibody, determined as percent of total IgA. Challenge with virulent strain H-10407 (5 X 10(9) living cells) produced diarrhea in 8 of 9 (89%) of the placebo-treated volunteers and in 2 of 10 (20%) of the vaccinees. Thus, the colicin E2-killed whole cell vaccine afforded both a significant intestinal immune response and significant protection against challenge with the virulent organism. The data presented here suggest that for this vaccine preparation an intestinal anti-CFA/I IgA response is a good indicator of a protective immune response, which most likely involves antibody responses to a number of antigens in addition to CFA/I. We conclude that the colicin E2 method for preparing an oral anti-ETEC vaccine merits further study and that this method may also be applicable to other enteropathogens.
authors.affiliation: Mucosal Immunity Laboratory, Veterans Administration Medical Center, Houston, Texas 77211.
authors.forename: D J
authors.initials: DJ
authors.lastname: Evans
authors.forename: D G
authors.initials: DG
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; D001428:Bacterial Vaccines / Q000276:immunology*; D002876:Chromosomes, Bacterial / Q000187:drug effects*; D003087:Colicins / Q000494:pharmacology*; D004269:DNA, Bacterial / Q000187:drug effects*; D003967:Diarrhea / Q000517:prevention & control*; D004926:Escherichia coli / Q000235:genetics / Q000276:immunology*; D004927:Escherichia coli Infections / Q000517:prevention & control*; D005260:Female; D006801:Humans; D007070:Immunoglobulin A / Q000032:analysis; D007074:Immunoglobulin G / Q000032:analysis; D008297:Male; D014611:Vaccination
chemical_list: D001428:Bacterial Vaccines; D003087:Colicins; D004269:DNA, Bacterial; D007070:Immunoglobulin A; D007074:Immunoglobulin G