Open AccessNon‐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
Author(s) -
Evans Dolores G.,
Evans Doyle J.,
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.tb02363.x
Subject(s) - enterotoxigenic escherichia coli , microbiology and biotechnology , antigen , enterotoxin , biology , heat labile enterotoxin , virology , heat stable enterotoxin , colicin , virulence , escherichia coli , immune system , serotype , plasmid , immunology , dna , genetics , biochemistry , gene
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 3×10 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. That protection against challenge with heterologous ETEC was due to non‐specific immunostimulation proved to be unlikely since only 1 of the remaining 6 vaccinees showed mild symptoms when challenged with strain H‐10407 6 months after vaccination. These results indicate that ETEC heterologous with respect to O, H, and CFA may share other antigens which contribute to a protective intestinal immune response.