Open AccessImmunoprotective oral whole cell vaccine for enterotoxigenic Escherichia coli diarrhea prepared by in situ destruction of chromosomal and plasmid DNA with colicin E2
Author(s) -
Evans Doyle J.,
Evans Dolores G.,
Opekun Antone R.,
Graham David Y.
Publication year - 1988
Publication title -
fems microbiology letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.899
H-Index - 151
eISSN - 1574-6968
pISSN - 0378-1097
DOI - 10.1111/j.1574-6968.1988.tb02485.x
Subject(s) - enterotoxigenic escherichia coli , microbiology and biotechnology , virulence , colicin , immune system , virology , biology , diarrhea , antigen , dna vaccination , escherichia coli , vibrio cholerae , antibody , immunization , plasmid , immunology , enterotoxin , medicine , dna , bacteria , biochemistry , genetics , gene
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 × 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 × 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.