Cross-Protection by B Subunit-Whole Cell Cholera Vaccine Against Diarrhea Associated with Heat-Labile Toxin-Producing Enterotoxigenic Escherichia coli: Results of a Large-Scale Field Trial

Clemens, John D.; Sack, David A.; Harris, Jeffrey R.; Chakraborty, J.; Neogy, P. K.; Stanton, Bonita; Huda, Nurul; Khan, Shafiqul Islam; B, Kay; Ansaruzzaman, M.; Yunus, Mohammad; Rao, Malla R.; Svennerholm, Ann‐Mari; Holmgren, Jan

doi:10.1093/infdis/158.2.372

Cited by 320 publications

(136 citation statements)

References 18 publications

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“…However, there is an oral cholera vaccine composed of killed wholecell Vibrio cholera, plus the B subunit of cholera toxin, which provides some cross-protection against LT-and LT/ ST-producing strains of ETEC. 13,14 The basis for the crossprotective efficacy of the cholera vaccine lies in the fact that the LT of ETEC is antigenically similar to cholera toxin in that it can elicit sufficient cross-reacting antibodies to LT. 13 Although anti-LT immunity is important in disease prevention, many ETEC isolates produce ST without LT. 4 ST is poorly antigenic and unrelated to LT, so other common antigens must be evaluated as potential vaccine components.…”

Section: Introductionmentioning

confidence: 99%

Toxins and colonization factor antigens of enterotoxigenic Escherichia coli among residents of Jakarta, Indonesia.

Oyofo¹,

Subekti²,

Svennerholm³

et al. 2001

The American Journal of Tropical Medicine and Hygiene

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Abstract. Infection caused by enterotoxigenic Escherichia coli (ETEC) poses a serious health problem among children and adults in developing countries. Colonization of the small intestinal mucosa by ETEC strains is mediated by antigenically specific fimbriae, also known as colonization factor antigens (CFA). The significance of this study arises from reports that active and passive immunization with ETEC strains harboring CFAs has previously been shown to induce protective immunity against diarrhea in animal models. The aim of this study was to determine toxin-associated CFAs of ETEC isolated from a diarrheal disease case-control study in Jakarta, Indonesia. Thirteen hundred and twenty-three diarrheic and control patients with lactose-fermenting colonies were screened by ganglioside GM1-enzyme-linked immunosorbent assay (GM1-ELISA) for heat-labile (LT) and heat-stable (ST) toxins. Two hundred and forty-six (19%) ETEC isolates identified by GM1-ELISA for the LT/ST toxins were screened for CFAs by Dot blot assay using monoclonal antibodies against CFA/I, II, and IV and against the putative colonization antigens (PCF) PCFO159, PCFO166, CS7, and CS17. Of the 246 ETEC isolates, 177 (72%) elaborated ST, 56 (23%) produced LT, while 13 (5%) elicited both the ST and LT toxins. CFA testing of the 246 ETEC isolates showed that 21 (8%) expressed CFA/I, 3 (1%) exhibited CFA/II, 14 (6%) elaborated CFA/IV, while 7 (3%) expressed PCFO159 and PCFO159 plus CS5. No CFAs or PCFs could be associated with 201 (82%) of the ETEC strains. This report documents the types of CFAs associated with ETEC strains in Jakarta, Indonesia. These data may help current research efforts on the development of CFA-based vaccines for humans against ETEC and provide additional information for future ETEC vaccine trials in Southeast Asia.

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Section: Introductionmentioning

confidence: 99%

Toxins and colonization factor antigens of enterotoxigenic Escherichia coli among residents of Jakarta, Indonesia.

Oyofo¹,

Subekti²,

Svennerholm³

et al. 2001

The American Journal of Tropical Medicine and Hygiene

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“…In addition, previous studies have shown that anti-LT immunity protects against ETEC-induced diarrhea in human (15)(16)(17). LT is structurally and biologically similar to CT (2,18), and several studies have demonstrated cross-protective immunity between CT and LT (19)(20)(21). It was therefore an obvious and important question to address whether CT-specific mucosal IgA induced by oral MucoRice-CTB vaccine could provide cross-protective immunity against LT-induced diarrhea and, if so, whether it could also provide protection against diarrhea induced by LT-producing ETEC (LT-ETEC).…”

mentioning

confidence: 99%

Secretory IgA-mediated protection againstV. choleraeand heat-labile enterotoxin-producing enterotoxigenicEscherichia coliby rice-based vaccine

Tokuhara

Yuki

Nochi

et al. 2010

Proc. Natl. Acad. Sci. U.S.A.

108

110

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Cholera and enterotoxigenic Escherichia coli (ETEC) are among the most common causes of acute infantile gastroenteritis globally. We previously developed a rice-based vaccine that expressed cholera toxin B subunit (MucoRice-CTB) and had the advantages of being cold chain-free and providing protection against cholera toxin (CT)-induced diarrhea. To advance the development of MucoRice-CTB for human clinical application, we investigated whether the CTB-specific secretory IgA (SIgA) induced by MucoRice-CTB gives longstanding protection against diarrhea induced by Vibrio cholerae and heatlabile enterotoxin (LT)-producing ETEC (LT-ETEC) in mice. Oral immunization with MucoRice-CTB stored at room temperature for more than 3 y provided effective SIgA-mediated protection against CTor LT-induced diarrhea, but the protection was impaired in polymeric Ig receptor-deficient mice lacking SIgA. The vaccine gave longstanding protection against CT-or LT-induced diarrhea (for ≥6 months after primary immunization), and a single booster immunization extended the duration of protective immunity by at least 4 months. Furthermore, MucoRice-CTB vaccination prevented diarrhea in the event of V. cholerae and LT-ETEC challenges. Thus, MucoRice-CTB is an effective long-term cold chain-free oral vaccine that induces CTBspecific SIgA-mediated longstanding protection against V. choleraeor LT-ETEC-induced diarrhea. cholera toxin B subunit | mucosal vaccine | oral vaccine | plant-made vaccine | MucoRice

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“…A vaccine that offers some protection against diarrhea caused by infections with strains producing LT is already available (3). In contrast to LT, STp and STh are small molecules that normally do not induce an immune response (12).…”

mentioning

confidence: 99%

Clonal Relatedness of Enterotoxigenic Escherichia coli Strains Isolated from a Cohort of Young Children in Guinea-Bissau

et al. 2004

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In a cohort study of 200 young children in Guinea-Bissau, it was previously found that some enterotoxigenic Escherichia coli (ETEC) strains were more pathogenic than others, depending on the type of toxin that they could produce, and that natural ETEC infections induced substantial protection against new infections with ETEC strains that had the same combination of toxins and colonization factors (CFs). We wanted to describe the clonal relatedness of the ETEC strains isolated during this study and to investigate whether the protective antigens and the virulence factors that were responsible for the pathogenic traits were common to strains that were clonally closely related or whether they were more likely to be encoded by the ETEC virulence plasmids that normally encode the toxins and the CFs. By performing repetitive sequence-based PCR analysis of strains representing 452 infections, we found that strains that had the same toxin-CF profile were usually closely related, although a few were unrelated. Strains that did not have the same toxin-CF profiles but that were positive for a given toxin or for a given CF were not consistently more closely related to each other than to strains that were negative for the same toxin or CF. Our results indicate that the pathogenic traits of ETEC were mainly attributed to genes carried on the ETEC virulence plasmids. Because most strains that had the same toxin-CF profile were closely related, it seems likely that the toxin-CF-specific protection was clonal and was not targeting antigens encoded by the virulence plasmids. These results are of relevance to the ETEC vaccine development effort.

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Cross-Protection by B Subunit-Whole Cell Cholera Vaccine Against Diarrhea Associated with Heat-Labile Toxin-Producing Enterotoxigenic Escherichia coli: Results of a Large-Scale Field Trial

Cited by 320 publications

References 18 publications

Toxins and colonization factor antigens of enterotoxigenic Escherichia coli among residents of Jakarta, Indonesia.

Toxins and colonization factor antigens of enterotoxigenic Escherichia coli among residents of Jakarta, Indonesia.

Secretory IgA-mediated protection againstV. choleraeand heat-labile enterotoxin-producing enterotoxigenicEscherichia coliby rice-based vaccine

Clonal Relatedness of Enterotoxigenic Escherichia coli Strains Isolated from a Cohort of Young Children in Guinea-Bissau

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