Skin immune responses to peptide and protein antigen are TLR4 independent

Kahlon, Roopjeet; Dutz, Jan P.

doi:10.1016/j.cellimm.2003.11.007

Cited by 5 publications

(3 citation statements)

References 42 publications

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“…immune responses in TLR4-defective C3H/HeJ mice compared with that in wild-type mice. Accordingly, the stronger Th1-inducing effect of CTA1-DD relative to that of CT seems not to be an effect of endotoxin contamination, and thus, is independent of TLR4 signaling (64). These findings render support for the idea that the ADP-ribosyltransferase-mediated adjuvant function is unique and different from other microbial adjuvants, of which many elicit proinflammatory responses (33).…”

Section: Discussionsupporting

confidence: 68%

The Cholera Toxin-Derived CTA1-DD Vaccine Adjuvant Administered Intranasally Does Not Cause Inflammation or Accumulate in the Nervous Tissues

Eriksson

Schön

Lycke

2004

The Journal of Immunology

106

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Although highly effective, the use of GM1-receptor binding holotoxins as nasal mucosal adjuvants has recently been cautioned due to the risk for their accumulation in the brain and other nervous tissues. Therefore we have explored the efficacy of the CTA1-DD adjuvant for its ability to enhance nasal immune responses in mice. We found that despite the lack of a mucosal binding element, the B cell-targeted CTA1-DD molecule was an equally strong adjuvant as cholera toxin (CT). The potency of CTA1-DD was not a result of endotoxin contamination because more than a 50-fold higher dose of LPS was needed to achieve a similar enhancement. Moreover, the adjuvant effect was TLR4-independent and absent in mutant CTA1-E112K-DD, lacking enzymatic activity. The CTA1-DD adjuvant augmented germinal center formations and T cell priming in the draining lymph nodes, and contrary to CT, promoted a balanced Th1/Th2 response with little effect on IgE Ab production. CTA1-DD did not induce inflammatory changes in the nasal mucosa, and most importantly did not bind to or accumulate in the nervous tissues of the olfactory bulb, whereas CT bound avidly to the nervous tissues. We believe that the nontoxic CTA1-DD adjuvant is an attractive solution to the current dilemma between efficacy and toxicity encountered in CT-holotoxin adjuvant or Escherichia coli heat-labile toxin-holotoxin adjuvant strategies and provides a safe and promising candidate to be included in future vaccines for intranasal administration.

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Section: Discussionsupporting

confidence: 68%

The Cholera Toxin-Derived CTA1-DD Vaccine Adjuvant Administered Intranasally Does Not Cause Inflammation or Accumulate in the Nervous Tissues

Eriksson

Schön

Lycke

2004

The Journal of Immunology

106

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“…[8][9][10] TCI has also shown to be effective at inducing cellular immune responses against cholera toxin (CT) and other viral product when peptides were used as immunogens. 7,11,12 Several types of adjuvants have been tested for their ability to enhance the immune responses by TCI. For example, ADPribosylating exotoxins including CT and heat-labile enterotoxin (LT) produced by Vibrio cholerae and Escherichia coli, respectively, have been reported to augment systemic humoral and cellular immune responses when used as adjuvants in TCI.…”

mentioning

confidence: 99%

Transcutaneous Immunization with Cytotoxic T-Cell Peptide Epitopes Provides Effective Antitumor Immunity in Mice

Itoh

Celis

2005

Journal of Immunotherapy

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Much attention has been focused on transcutaneous immunization strategies to stimulate systemic cytotoxic T lymphocyte responses leading to anti-tumor or anti-microbial immunity. Here we report that topical application of vaccines consisting of synthetic peptides formulated with imiquimod, a Toll-like receptor agonist that functions as a potent adjuvant generates strong T cell responses that exhibit effective anti-tumor effects in a murine melanoma model system. These results support the use of peptide-based transcutaneous vaccines as a noninvasive and effective strategy for anti-tumor immunotherapy.

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“…Recently, bacterial lipopolysaccharide (LPS) has become an attractive adjuvant for TCI. According to Kahlon and Dutz ( 2003 ), LPS and its derivatives can activate TLR4 expressed by LCs and DCs. Additionally, Quil A (QA) has been incorporated into TCI formulations to enhance skin penetration and immune responses (Madsen et al 2009 ).…”

Section: Immune Modulators For Transcutaneous Immunizationmentioning

confidence: 99%