A novel concept in mucosal adjuvanticity: the CTA1-DD adjuvant is a B cell-targeted fusion protein that incorporates the enzymatically active cholera toxin A1 subunit.
A promising novel concept in mucosal adjuvant research is demonstrated here. The adjuvant and toxic effects of the cholera toxin (CT) have been successfully separated in a gene fusion protein, CTA1-DD. This protein consists of the ADP-ribosylating A1 subunit of CT linked to a synthetic analogue of protein A. The CTA1-DD protein was found to exert comparable adjuvant activity to that of CT after systemic as well as mucosal immunizations with soluble protein antigens, such as KLH or ovalbumin (OVA). However, contrary to CT it was completely non-toxic. The CTA1-DD approach to the construction of a potential vaccine adjuvant is unique and highly promising. Conceptually, the CTA1-DD fusion protein demonstrates that: (i) contrary to CT the CTA1-DD is a highly targeted adjuvant, directed to B cells and possibly other antigen-presenting cells; (ii) it is possible to introduce ADP-ribosyltransferase activity into cells via an alternative pathway to the GM1 receptor pathway used by CTB; (iii) the adjuvant effect of CTA1-DD, and possibly also of CT, depend on the enzymatic activity; and (iv) one possible mechanism, shared by CT, that may explain the adjuvant effect of CTA1-DD is its ability to induce expression of the costimulatory molecule CD86 on B cells.
Department of Medical Microbiology and Immunology, University of Göteborg, Sweden.
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Agren
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Löwenadler
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Lycke
D000276:Adjuvants, Immunologic / Q000008:administration & dosage* / Q000235:genetics; D000284:Administration, Oral; D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D002772:Cholera Toxin / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology*; D004789:Enzyme Activation / Q000276:immunology; D018390:Gene Targeting; D006801:Humans; D018928:Immunity, Mucosal / Q000235:genetics; D011993:Recombinant Fusion Proteins / Q000008:administration & dosage* / Q000276:immunology*
D000276:Adjuvants, Immunologic; D011993:Recombinant Fusion Proteins; D002772:Cholera Toxin