Show simple item record

dc.contributor.authorGiuliani, MM
dc.contributor.authorDel Giudice, G
dc.contributor.authorGiannelli, V
dc.contributor.authorDougan, G
dc.contributor.authorDouce, G
dc.contributor.authorRappuoli, R
dc.contributor.authorPizza, M
dc.date.accessioned2021-02-04T01:52:16Z
dc.date.available2021-02-04T01:52:16Z
dc.date.issued1998-04-06
dc.identifier.citationGiuliani, M. M., Del Giudice, G., Giannelli, V., Dougan, G., Douce, G., Rappuoli, R. & Pizza, M. (1998). Mucosal adjuvanticity and immunogenicity of LTR72, a novel mutant of Escherichia coli heat-labile enterotoxin with partial knockout of ADP-ribosyltransferase activity.. J Exp Med, 187 (7), pp.1123-1132. https://doi.org/10.1084/jem.187.7.1123.
dc.identifier.issn0022-1007
dc.identifier.urihttp://hdl.handle.net/11343/259502
dc.description.abstractHeat-labile Escherichia coli enterotoxin (LT) has the innate property of being a strong mucosal immunogen and adjuvant. In the attempt to reduce toxicity and maintain the useful immunological properties, several LT mutants have been produced. Some of these are promising mucosal adjuvants. However, so far, only those that were still toxic maintained full adjuvanticity. In this paper we describe a novel LT mutant with greatly reduced toxicity that maintains most of the adjuvanticity. The new mutant (LTR72), that contains a substitution Ala --> Arg in position 72 of the A subunit, showed only 0.6% of the LT enzymatic activity, was 100,000-fold less toxic than wild-type LT in Y1 cells in vitro, and was at least 20 times less effective than wild-type LT in the rabbit ileal loop assay in vivo. At a dose of 1 microg, LTR72 exhibited a mucosal adjuvanticity, similar to that observed with wild-type LT, better than that induced by the nontoxic, enzymatically inactive LTK63 mutant, and much greater than that of the recombinant B subunit. This trend was consistent for both the amounts and kinetics of the antibody induced, and priming of antigen-specific T lymphocytes. The data suggest that the innate high adjuvanticity of LT derives from the independent contribution of the nontoxic AB complex and the enzymatic activity. LTR72 optimizes the use of both properties: the enzymatic activity for which traces are enough, and the nontoxic AB complex, the effect of which is dose dependent. In fact, in dose-response experiments in mice, 20 microg of LTR72 were a stronger mucosal adjuvant than wild-type LT. This suggests that LTR72 may be an excellent candidate to be tested in clinical trials.
dc.languageeng
dc.publisherRockefeller University Press
dc.rights.urihttps://creativecommons.org/licenses/by-nc-sa/4.0
dc.titleMucosal adjuvanticity and immunogenicity of LTR72, a novel mutant of Escherichia coli heat-labile enterotoxin with partial knockout of ADP-ribosyltransferase activity.
dc.typeJournal Article
dc.identifier.doi10.1084/jem.187.7.1123
melbourne.affiliation.departmentMicrobiology and Immunology
melbourne.affiliation.facultyMedicine, Dentistry & Health Sciences
melbourne.source.titleJournal of Experimental Medicine
melbourne.source.volume187
melbourne.source.issue7
melbourne.source.pages1123-1132
dc.rights.licenseCC BY-NC-SA
melbourne.elementsid1080693
melbourne.openaccess.pmchttp://www.ncbi.nlm.nih.gov/pmc/articles/PMC2212201
melbourne.contributor.authorDougan, Gordon
dc.identifier.eissn1540-9538
melbourne.accessrightsOpen Access


Files in this item

Thumbnail

This item appears in the following Collection(s)

Show simple item record