Actions of cholera toxin and the prevention and treatment of cholera

Holmgren, Jan

doi:10.1038/292413a0

Cited by 512 publications

(265 citation statements)

References 93 publications

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“…treatment with OVA/CTB conjugate is probably largely explained by the effects of the conjugate on gut mucosal APC. Previous studies have shown that conjugation of Ag to CTB, a molecule that binds with high affinity to the GM1 ganglioside receptors present on most cells (30), greatly facilitates Ag uptake and MHC class II-restricted Ag presentation by CD11c ϩ DC as well as other types of APC, such as B cells and macrophages (23). One possibility is that mucosally administered Ag/CTB conjugate preferentially binds to and is taken up by tolerogenic subsets of mucosal DC or other APC.…”

Section: Discussionmentioning

confidence: 99%

Oral Tolerance Induction with Antigen Conjugated to Cholera Toxin B Subunit Generates Both Foxp3+CD25+ and Foxp3−CD25− CD4+ Regulatory T Cells

Sun

Raghavan

Sjöling

et al. 2006

The Journal of Immunology

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103

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Oral administration of Ag coupled to cholera toxin B subunit (CTB) efficiently induces peripheral immunological tolerance. We investigated the extent to which this oral tolerance is mediated by CD25+CD4+ regulatory T cells (Treg). We found that total Treg, KJ1–26+ Treg and CTLA-4+ Treg were all increased in Peyer’s patches, mesenteric lymph nodes, and, to a lesser extent, in spleen of mice after intragastric administration of OVA/CTB conjugate, which also increased TGF-β in serum. This could be abolished by coadministering cholera toxin or by treatment with anti-TGF-β mAb. CD25+ Treg, but also CD25−CD4+ T cells from OVA/CTB-treated BALB/c or DO11.10 mice efficiently suppressed effector T cell proliferation and IL-2 production in vitro. Following adoptive transfer, both T cell populations also suppressed OVA-specific T cell and delayed-type hypersensitivity responses in vivo. Foxp3 was strongly expressed by CD25+ Treg from OVA/CTB-treated mice, and treatment also markedly expanded CD25+Foxp3+ Treg. Furthermore, in Rag1−/− mice that had adoptively received highly purified Foxp3−CD25−CD4+ OT-II T cells OVA/CTB feeding efficiently induced CD25+ Treg cells, which expressed Foxp3 more strongly than naturally developing Treg and also had stronger ability to suppress effector OT-II T cell proliferation. A remaining CD25− T cell population, which also became suppressive in response to OVA/CTB treatment, did not express Foxp3. Our results demonstrate that oral tolerance induced by CTB-conjugated Ag is associated with increase in TGF-β and in both the frequency and suppressive capacity of Foxp3+ and CTLA-4+ CD25+ Treg together with the generation of both Foxp3+ and Foxp3−CD25− CD4+ Treg.

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Section: Discussionmentioning

confidence: 99%

Oral Tolerance Induction with Antigen Conjugated to Cholera Toxin B Subunit Generates Both Foxp3+CD25+ and Foxp3−CD25− CD4+ Regulatory T Cells

Sun

Raghavan

Sjöling

et al. 2006

The Journal of Immunology

Self Cite

103

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“…It is now clear that mucosal vaccination can induce both memory IgA + and memory IgG + B cells after oral, intranasal and intravaginal vaccinations [67]. Studies showed protection against infection induced by mucosal vaccines can last for several years, even though intestinal IgA responses vanish after 6-9 months [68][69][70]. For caries vaccines, the duration of salivary IgA responses induced by mucosal immunization need to be explored further.…”

Section: Development Of a Nasal-spray Or Nasal-drop Anti-caries Vaccimentioning

confidence: 99%

Salivary IgA enhancement strategy for development of a nasal-spray anti-caries mucosal vaccine

Yan

2013

Sci. China Life Sci.

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Dental caries remains one of the most common global chronic diseases caused by Streptococcus mutans, which is prevalent all over the world. The caries prevalence of children aged between 5-6 years old in China is still in very high rate. A potent and effective anti-caries vaccine has long been expected for caries prevention but no vaccines have been brought to market till now mainly due to the low ability to induce and maintain protective antibody in oral fluids. This review will give a brief historical retrospect on study of dental caries and pathogenesis, effective targets for anti-caries vaccines, oral immune system and immunization against dental caries. Then, salivary IgA antibodies and the protective responses are discussed in the context of the ontogeny of mucosal immunity to indigenous oral streptococcal. The methods and advancement for induction of specific anticaries salivary sIgA antibodies and enhancement of specific anti-caries salivary sIgA antibodies by intranasal immunization with a safe effective mucosal adjuvant are described. The progress in the enhancement of salivary sIgA antibodies and anticaries protection by intranasal immunization with flagellin-PAc fusion protein will be highlighted. Finally, some of the main strategies that have been used for successful mucosal vaccination of caries vaccine are reviewed, followed by discussion of the mucosal adjuvant choice for achieving protective immunity at oral mucosal membranes for development of a nasal-spray or nasal-drop anti-caries vaccine for human. mutans streptococci, secretory IgA, PAc, mucosal immunization, caries vaccine Citation:Yan H M. Salivary IgA enhancement strategy for development of a nasal-spray anti-caries mucosal vaccine.

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“…By comparative studies of the small intestinal mucosa in man, pig and beef we showed that there was a direct relation between the binding ability for cholera toxin and the ganglioside GM1 content [2], which suggested that ganglioside GM1 is the natural specific receptor for cholera toxin. Intestinal mucosa of adult man had a remarkably low concentration of ganglioside GM1 , and it was of importance both from a theoretical point of view, but also for the profylaxis and treatment of cholera and allied intestinal infectious diseases [3] to know the actu,al ganglioside GM1 concentration in intestinal mucosa during development. For the determination of the ganglioside concentration during the fetal stage we used meconium, which is the fist faeces of the newborn and consists mainly of extruded mucosal cells from the intestine.…”

Section: Introductionmentioning

confidence: 99%