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Mutants of Escherichia coli heat-labile toxin lacking ADP-ribosyltransferase activity act as nontoxic, mucosal adjuvants.
Open accessAbstract
A nontoxic mutant (LTK7) of the Escherichia coli heat-labile enterotoxin (LT) lacking ADP-ribosylating activity but retaining holotoxin formation was constructed. By using site-directed mutagenesis, the arginine at position 7 of the A subunit was replaced with lysine. This molecule, which was nontoxic in several assays, was able to bind to eukaryotic cells and acted as a mucosal adjuvant for co-administered proteins; BALB/c mice immunized intranasally with LTK7 and ovalbumin developed high levels of serum and local antibodies to ovalbumin and toxin. In addition, mice immunized intranasally with fragment C of tetanus toxin and LTK7 were protected against lethal challenge with tetanus toxin. Thus nontoxic mutants of heat-labile toxin can act as effective intranasal mucosal adjuvants.
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Citations
Cited by
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Kiyono, H., & Fukuyama, S. (2004) · Nature Reviews Immunology · doi:10.1038/nri1439 · Cited by 745
INTERACTION OF ANTIGENS AND ANTIBODIES AT MUCOSAL SURFACES
Lamm, M. E. (1997) · Annual Review of Microbiology · doi:10.1146/annurev.micro.51.1.311 · Cited by 429
Michetti, P., Kreiss, C., Kotloff, K. L., Porta, N., Blanco, J., Bachmann, D., Herranz, M., Saldinger, P. F., Corthésy–Theulaz, I., Losonsky, G., et al. (1999) · Gastroenterology · doi:10.1016/s0016-5085(99)70063-6 · Cited by 310
Norton, E. B., Lawson, L. B., Freytag, L. C., & Clements, J. D. (2011) · Clinical and Vaccine Immunology · doi:10.1128/cvi.00538-10 · Cited by 221
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O’Hagan, D. T., & Singh, M. (2003) · Expert Review of Vaccines · doi:10.1586/14760584.2.2.269 · Cited by 214
Metadata
- Authors
- Douce, G., Turcotte, C., Cropley, I., Roberts, M., Pizza, M., Domenghini, M., Rappuoli, R., & Dougan, G.
- Venue
- Proceedings of the National Academy of Sciences
- Published
- 1995-02-28
- Volume
- 92
- Issue
- 5
- Pages
- 1644-1648
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- OpenAlex
- W2012188057
- Cited by
- 278
- References
- 0
- FWCI
- 8.73
- Type
- journal article
- Language
- en
- Open access
- green
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- CoChat. (2026). Citation check: Mutants of Escherichia coli heat-labile toxin lacking ADP-ribosyltransferase activity act as nontoxic, mucosal adjuvants. https://app.cochat.ai/papers/10.1073/pnas.92.5.1644
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- Douce, G., Turcotte, C., Cropley, I., Roberts, M., Pizza, M., Domenghini, M., Rappuoli, R., & Dougan, G. (1995). Mutants of Escherichia coli heat-labile toxin lacking ADP-ribosyltransferase activity act as nontoxic, mucosal adjuvants. Proceedings of the National Academy of Sciences. https://doi.org/10.1073/pnas.92.5.1644
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Bibliographic data: Semantic Scholar, OpenAlex, Crossref.
Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
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