Musosal immunoadjuvant activity of recombinant Escherichia coli heatlabile enterotoxin and its B subunit: Induction of systemic IgG and secretory IgA responses in mice by intranasal immunization with influenza virus surface antigen

Verweij, Walter; Haan, Lolke de; Holtrop, Marijke; Agsteribbe, E; Brands, Ruud; Scharrenburg, Gjm van; Wilschut, Jan

doi:10.1016/s0264-410x(98)00076-0

Cited by 82 publications

(63 citation statements)

References 42 publications

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“…As viral glycoproteins were not themselves immunogenic in this system, these findings indicate that the B subunit of Etx can act as an adjuvant for HSV antigens without a requirement for the ADP ribosylation activity of the A subunit. This finding is consistent with other recent studies, where EtxB has been shown to act as an intranasal adjuvant for influenza virus hemagglutinin and ovalbumin (8,36). Interestingly, rCtxB was not capable of acting as an adjuvant for the HSV-1 glycoproteins.…”

Section: Discussionsupporting

confidence: 93%

Protective Mucosal Immunity to Ocular Herpes Simplex Virus Type 1 Infection in Mice by UsingEscherichia coliHeat-Labile Enterotoxin B Subunit as an Adjuvant

Richards

Aman

Hirst

et al. 2001

J Virol

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The potential of nontoxic recombinant B subunits of cholera toxin (rCtxB) and its close relative Escherichia coli heat-labile enterotoxin (rEtxB) to act as mucosal adjuvants for intranasal immunization with herpes simplex virus type 1 (HSV-1) glycoproteins was assessed. Doses of 10 g of rEtxB or above with 10 g of HSV-1 glycoproteins elicited high serum and mucosal anti-HSV-1 titers comparable with that obtained using CtxB (10 g) with a trace (0.5 g) of whole toxin (Ctx-CtxB). By contrast, doses of rCtxB up to 100 g elicited only meager anti-HSV-1 responses. As for Ctx-CtxB, rEtxB resulted in a Th2-biased immune response with high immunoglobulin G1 (IgG1)/IgG2a antibody ratios and production of interleukin 4 (IL-4) and IL-10 as well as gamma interferon by proliferating T cells. The protective efficacy of the immune response induced using rEtxB as an adjuvant was assessed following ocular challenge of immunized and mock-immunized mice. Epithelial disease was observed in both groups, but the immunized mice recovered by day 6 whereas mock-immunized mice developed more severe corneal disease leading to stromal keratitis. In addition, a significant reduction in the incidence of lid disease and zosteriform spread was observed in immunized animals and there was no encephalitis compared with 95% encephalitis in mock-immunized mice. The potential of such mucosal adjuvants for use in human vaccines against pathogens such as HSV-1 is discussed.

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Section: Discussionsupporting

confidence: 93%

Protective Mucosal Immunity to Ocular Herpes Simplex Virus Type 1 Infection in Mice by UsingEscherichia coliHeat-Labile Enterotoxin B Subunit as an Adjuvant

Richards

Aman

Hirst

et al. 2001

J Virol

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“…One of the most unexpected and striking effects of the B subunits is their capacity to trigger the selective apoptosis of CD8 ϩ T cells, as well as to alter CD4 ϩ T-cell differentiation, activate B cells, and modulate antigen processing and presentation by macrophages (5). These potent immunological properties have led to testing of the B subunits as adjuvants for stimulating mucosal and systemic responses to coadministered antigens (6,7) and as agents for down-regulating proinflammatory autoimmune diseases such as rheumatoid arthritis and diabetes (8)(9)(10).…”

mentioning

confidence: 99%

A mutant cholera toxin B subunit that binds GM1- ganglioside but lacks immunomodulatory or toxic activity

Aman

Fraser

Merritt

et al. 2001

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

104

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GM1-ganglioside receptor binding by the B subunit of cholera toxin (CtxB) is widely accepted to initiate toxin action by triggering uptake and delivery of the toxin A subunit into cells. More recently, GM1 binding by isolated CtxB, or the related B subunit of Escherichia coli heat-labile enterotoxin (EtxB), has been found to modulate leukocyte function, resulting in the down-regulation of proinflammatory immune responses that cause autoimmune disorders such as rheumatoid arthritis and diabetes. Here, we demonstrate that GM1 binding, contrary to expectation, is not sufficient to initiate toxin action. We report the engineering and crystallographic structure of a mutant cholera toxin, with a His to Ala substitution in the B subunit at position 57. Whereas the mutant retained pentameric stability and high affinity binding to GM1-ganglioside, it had lost its immunomodulatory activity and, when part of the holotoxin complex, exhibited ablated toxicity. The implications of these findings on the mode of action of cholera toxin are discussed.

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“…A nontoxic, enzymatically inactive mutant LT (LTE- 112K) was shown to lack adjuvanticity in oral immunization in mice, suggesting that ADP-ribosyltransferase activity may be required for adjuvanticity (Lycke et al, 1992). However, when delivered via the IN route, the same mutant LTE112K has been shown to exert adjuvant activity (Verweij et al, 1998). On the other hand, Giuliani et al (1998) indicated that enzymatic activity is required for full mucosal adjuvanticity by demonstrating that LTR72, which had only 0.6% of wild-type LT enzymatic activity, exhibited a greater mucosal adjuvanticity than the nontoxic, enzymatically inactive mutant LTK63 .…”

Section: Discussionmentioning

confidence: 99%

The mucosal adjuvanticity of two nontoxic mutants of Escherichia coli heat-labile enterotoxin varies with immunization routes

Park¹,

Chang²,

Kim³

et al. 2000

Exp Mol Med

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Escherichia coli heat-labile enterotoxin (LT), which causes a characteristic diarrhea in humans and animals, is a strong mucosal immunogen and has powerful mucosal adjuvant activity towards coadministered unrelated antigens. Here we report the different mucosal adjuvanticity of nontoxic LT derivatives, LTS63Y and LT∆110/112, generated by immunizing through two different mucosal routes. Intragastric (

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Musosal immunoadjuvant activity of recombinant Escherichia coli heatlabile enterotoxin and its B subunit: Induction of systemic IgG and secretory IgA responses in mice by intranasal immunization with influenza virus surface antigen

Cited by 82 publications

References 42 publications

Protective Mucosal Immunity to Ocular Herpes Simplex Virus Type 1 Infection in Mice by UsingEscherichia coliHeat-Labile Enterotoxin B Subunit as an Adjuvant

Protective Mucosal Immunity to Ocular Herpes Simplex Virus Type 1 Infection in Mice by UsingEscherichia coliHeat-Labile Enterotoxin B Subunit as an Adjuvant

A mutant cholera toxin B subunit that binds GM1- ganglioside but lacks immunomodulatory or toxic activity

The mucosal adjuvanticity of two nontoxic mutants of Escherichia coli heat-labile enterotoxin varies with immunization routes

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