A Nontoxic Chimeric Enterotoxin Adjuvant Induces Protective Immunity in Both Mucosal and Systemic Compartments with Reduced IgE Antibodies

Kweon, Mi‐Na; Yamamoto, Masafumi; Watanabe, Fumiko; Tamura, Shinichi; Ginkel, Frederik W. van; Miyauchi, Akira; Takagi, Hiroaki; Takeda, Yoshifumi; Hamabata, Takashi; Fujihashi, Kohtaro; McGhee, Jerry R.; Kiyono, Hiroshi

doi:10.1086/344526

Cited by 67 publications

(61 citation statements)

References 40 publications

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“…Our finding that oral delivery of PPE and CT promotes higher levels of peanut-specific IgE responses than nasal delivery is consistent with earlier reports suggesting that Peyer's patches of the GI tract are preferred sites of IgE Ab responses. 50,51 High IgE responses have been reported after nasal administration of mice with several protein antigens in the presence of CT. 34,[52][53][54] High levels of antigen-specific IgE Abs were also measured when OVA was used instead of PPE in our nasal sensitization studies (data not shown). Peanut contains a large number of proteins, and the biological activity of most of them has not been carefully investigated.…”

Section: Discussionmentioning

confidence: 83%

Oral and Nasal Sensitization Promote Distinct Immune Responses and Lung Reactivity in a Mouse Model of Peanut Allergy

Fischer

McGhee

et al. 2005

The American Journal of Pathology

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Despite structural and functional differences between the initial sites of contact with allergens in the gastrointestinal and nasal tracts, few animal models have examined the influence of the mucosal routes of sensitization on host reactivity to food or environmental antigens. We compared the oral and nasal routes of peanut sensitization for the development of a mouse model of allergy. Mice were sensitized by administration of peanut proteins in the presence of cholera toxin as adjuvant. Antibody and cytokine responses were characterized, as well as airway reactivity to nasal challenge with peanut or unrelated antigens. Oral sensitization promoted higher levels of IgE, but lower IgG responses, than nasal sensitization. Both orally and nasally sensitized mice experienced airway hyperreactivity on nasal peanut challenge. The peanut challenge also induced lung eosinophilia and type 2 helper T-cell-type cytokines in orally sensitized mice. In contrast, peanut challenge in nasally sensitized mice promoted neutrophilia and higher levels of The prevalence of peanut allergy has doubled in the last decade, and it now affects more than 3 million individuals in the United States.

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Section: Discussionmentioning

confidence: 83%

Oral and Nasal Sensitization Promote Distinct Immune Responses and Lung Reactivity in a Mouse Model of Peanut Allergy

Fischer

McGhee

et al. 2005

The American Journal of Pathology

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“…in both C57BL/6 and BALB/c mice (data not shown). Studies with the ganglioside-targeting enterotoxins CT and LT-I (52-55) and derivatives including their chimeras (34,56) or the B cell-targeting CTA1-DD (31,57) have demonstrated the importance of receptor binding for controlling the immune responses induced by these ADP-ribosylating adjuvants. Thus, the adjuvant activity of CT appears to be more dependent on IL-4 and CD4 ϩ Th2 cell cytokines (52,53).…”

Section: Discussionmentioning

confidence: 99%

“…The lower stimulatory effect of EdTx for IL-6 secretion was further confirmed in vivo where nasal delivery of CT but not EdTx induced IL-6 secretion in nasal washes. It is unlikely that the reduced ability of EdTx to induce IL-6 (and IL-1) could alone explain the polarized Ag-specific mucosal IgA Abs responses when compared with those generally induced by CT (34,46,63) or LT as adjuvants (34,46,54,56). The role of the adenylate cyclase activity for the adjuvanticity remains to be elucidated.…”

Section: Discussionmentioning

confidence: 99%

Bacillus anthracisEdema Toxin Acts as an Adjuvant for Mucosal Immune Responses to Nasally Administered Vaccine Antigens

Duverger

Jackson

Ginkel

et al. 2006

The Journal of Immunology

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Anthrax edema toxin (EdTx) is an AB-type toxin that binds to anthrax toxin receptors on target cells via the binding subunit, protective Ag (PA). Edema factor, the enzymatic A subunit of EdTx, is an adenylate cyclase. We found that nasal delivery of EdTx enhanced systemic immunity to nasally coadministered OVA and resulted in high OVA-specific plasma IgA and IgG (mainly IgG1 and IgG2b). The edema factor also enhanced immunity to the binding PA subunit itself and promoted high levels of plasma IgG and IgA responses as well as neutralizing PA Abs. Mice given OVA and EdTx also exhibited both PA- and OVA-specific IgA and IgG Ab responses in saliva as well as IgA Ab responses in vaginal washes. EdTx as adjuvant triggered OVA- and PA-specific CD4+ T cells which secreted IFN-γ and selected Th2-type cytokines. The EdTx up-regulated costimulatory molecule expression by APCs but was less effective than cholera toxin for inducing IL-6 responses either by APCs in vitro or in nasal washes in vivo. Finally, nasally administered EdTx did not target CNS tissues and did not induce IL-1 mRNA responses in the nasopharyngeal-associated lymphoepithelial tissue or in the olfactory bulb epithelium. Thus, EdTx derivatives could represent an alternative to the ganglioside-binding enterotoxin adjuvants and provide new tools for inducing protective immunity to PA-based anthrax vaccines.

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“…rCTB was expressed in Bacillus brevis and purified by using immobilized galactose (Pierce) (5,37). rLTB was expressed in Brevibacillus choshinensis and purified by using immobilized galactose (Pierce) as previously described, with some modification (38).…”

Section: Methodsmentioning

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.

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107

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 Nontoxic Chimeric Enterotoxin Adjuvant Induces Protective Immunity in Both Mucosal and Systemic Compartments with Reduced IgE Antibodies

Cited by 67 publications

References 40 publications

Oral and Nasal Sensitization Promote Distinct Immune Responses and Lung Reactivity in a Mouse Model of Peanut Allergy

Oral and Nasal Sensitization Promote Distinct Immune Responses and Lung Reactivity in a Mouse Model of Peanut Allergy

Bacillus anthracisEdema Toxin Acts as an Adjuvant for Mucosal Immune Responses to Nasally Administered Vaccine Antigens

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

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