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FEMS Microbiol Immunol. 1988 Jan;1(1):9-18.

Immunoprotective oral whole cell vaccine for enterotoxigenic Escherichia coli diarrhea prepared by in situ destruction of chromosomal and plasmid DNA with colicin E2.

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Mucosal Immunity Laboratory, Veterans Administration Medical Center, Houston, Texas 77211.


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.

[Indexed for MEDLINE]

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