CTA1-DD-Immune stimulating complexes: A novel, rationally designed combined mucosal vaccine adjuvant effective with nanogram doses of antigen

Mowat, A. M.I., Donachie, A. M., Jagewall, S., Schon, K., Lowenadler, B., Dalsgaard, K., Kaastrup, P. and Lycke, N. (2001) CTA1-DD-Immune stimulating complexes: A novel, rationally designed combined mucosal vaccine adjuvant effective with nanogram doses of antigen. Journal of Immunology, 167(6), pp. 3398-3405. (doi: 10.4049/​jimmunol.167.6.3398) (PMID:11544331)

Full text not currently available from Enlighten.

Abstract

Mucosally active vaccine adjuvants that will prime a full range of local and systemic immune responses against defined antigenic epitopes are much needed. Cholera toxin and lipophilic immune stimulating complexes (ISCOMS) containing Quil A can both act as adjuvants for orally administered Ags, possibly by targeting different APCs. Recently, we have been successful in separating the adjuvant and toxic effects of cholera toxin by constructing a gene fusion protein, CTA1-DD, that combines the enzymatically active CTA1-subunit with a B cell-targeting moiety, D, derived from Staphylococcus aureus protein A. Here we have extended this work by combining CTA1-DD with ISCOMS, which normally target dendritic cells and/or macrophages. ISCOMS containing a fusion protein comprising the OVA323–339 peptide epitope linked to CTA1-DD were highly immunogenic when given in nanogram doses by the s.c., oral, or nasal routes, inducing a wide range of T cell-dependent immune responses. In contrast, ISCOMS containing the enzymatically inactive CTA1-R7K-DD mutant protein were much less effective, indicating that at least part of the activity of the combined vector requires the ADP-ribosylating property of CTA1. No toxicity was observed by any route. To our knowledge, this is the first report on the successful combination of two mechanistically different principles of adjuvant action. We conclude that rationally designed vectors consisting of CTA1-DD and ISCOMS may provide a novel strategy for the generation of potent and safe mucosal vaccines.

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Mowat, Professor Allan and Donachie, Ms Anne Marie
Authors: Mowat, A. M.I., Donachie, A. M., Jagewall, S., Schon, K., Lowenadler, B., Dalsgaard, K., Kaastrup, P., and Lycke, N.
College/School:College of Medical Veterinary and Life Sciences
College of Medical Veterinary and Life Sciences > Institute of Infection Immunity and Inflammation
Journal Name:Journal of Immunology
Publisher:American Association of Immunologists
ISSN:0022-1767
ISSN (Online):1550-6606
Published Online:15 September 2001

University Staff: Request a correction | Enlighten Editors: Update this record