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From cholera to enterotoxigenic Escherichia coli (ETEC) vaccine development - PubMed

Review

. 2011 Feb;133(2):188-96.

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Review

From cholera to enterotoxigenic Escherichia coli (ETEC) vaccine development

Ann-Mari Svennerholm. Indian J Med Res. 2011 Feb.

Abstract

It was shown earlier that immune responses against cholera toxin (CT) as well as Vibrio cholerae lipopolysaccharide (LPS) or whole bacterial cells (WC) were protective and that these different antibody specificities co-operated synergistically for protection against experimental cholera. Similarly, antibodies against the heat-labile toxin (LT) and major colonization factors (CFs) of enterotoxingenic Escherichia coli (ETEC) co-operated synergistically for protection against LT-producing ETEC expressing homologous CFs. Studies in humans revealed that repeated oral antigen administration was optimal in inducing intestinal immune responses. Based on these findings oral inactivated vaccines consisting of toxin antigen and whole cells, i.e. the licensed recombinant cholera B subunit (rCTB)-WC cholera vaccine Dukoral®, and candidate ETEC vaccines have been developed. In different trials the rCTB-WC cholera vaccine has provided very high (85-100%) short term protection, which was significantly higher than that induced by the WC component alone, whereas rCTB-WC and WC alone provided comparable (50-60%), long term protection. An oral ETEC vaccine consisting of rCTB and formalin-inactivated E. coli bacteria expressing major CFs was shown to be safe and immunogenic in adults and children in different countries. The vaccine also induced significant protection against non-mild ETEC diarrhoea, i.e. diarrhoea interfering with daily activity in American travellers but not against ETEC diarrhoea in young children in Egypt. Against this background, a modified ETEC vaccine consisting of recombinant E. coli strains overexpressing the major CFs and a more LT like hybrid toxoid (LCTBA) has been developed. This vaccine will be tested soon alone and together with a mucosal adjuvant, i.e. dmLT, in clinical trials.

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Figures

Fig. 1
Fig. 1

Use of rabbit ileal loop technique for identification of protective antigens against cholera as a basis for vaccine development.

Fig. 2
Fig. 2

Rabbits subcutaneously immunized with 2 doses of V. cholerae LPS (1.25 mg/dose), CT (15 μg/dose) or a combination of the same doses of LPS and CT were challenged with graded doses of live vibrios, and ED50 for immunized rabbits were compared with those of PBS injected rabbits. Protection factors are indicated on y-axis.

Fig. 3
Fig. 3

Protection afforded by rabbit antisera against CFA/I, CFA/II (CS1+CS3) and LT against challenge with ETEC expressing homologous colonization factors (CFs) and LT in rabbit small bowel loops.

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