The B cell targeted adjuvant, CTA1-DD, exhibits potent mucosal immunoenhancing activity despite pre-existing anti-toxin immunity.
We recently developed a novel immunomodulating gene fusion protein, CTA1-DD, that combines the ADP-ribosylating ability of cholera toxin (CT) with a dimer of an Ig-binding fragment, D, of Staphylococcus aureus protein A. The CTA1-DD adjuvant was found to be non-toxic and greatly augmented T cell dependent and independent responses. Following injection it binds to both naïve and memory B cells and up-regulates co-stimulatory molecules as well as prevents apoptosis of activated B cells. Here we show that CTA1-DD is a potent mucosal adjuvant administered intranasally. A dose-response analysis revealed that the adjuvant effect of CTA1-DD given intranasally was equally strong to that observed after systemic immunizations. The adjuvant effect was independent of any possible contamination with endotoxin as indicated by the similar enhancing effects of CTA1-DD in C3H/HeN and the LPS-insensitive C3H/HeJ mice. Contrary to many other adjuvants CTA1-DD induces an immune response to itself. However, despite the presence of high serum titers of pre-existing anti-CTA1 antibodies we observed no reduction of the adjuvant function of CTA1-DD when given either intranasally or systemically. These results support the notion that the CTA1-DD adjuvant can repeatedly be used in the clinic without loss of efficacy even when pre-existing anti-CTA1 antibody levels are high.
Lycke
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Department of Clinical Immunology, University of Göteborg, S-413 46, Göteborg, Sweden. nils.lycke@microbio.gu.se
Schön
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D000276:Adjuvants, Immunologic / Q000008:administration & dosage / Q000494:pharmacology*; D000281:Administration, Intranasal; D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology*; D002772:Cholera Toxin / Q000008:administration & dosage / Q000276:immunology / Q000494:pharmacology*; D018928:Immunity, Mucosal; D051379:Mice; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D011993:Recombinant Fusion Proteins / Q000008:administration & dosage / Q000494:pharmacology; D013205:Staphylococcal Protein A / Q000008:administration & dosage / Q000494:pharmacology
D000276:Adjuvants, Immunologic; D011993:Recombinant Fusion Proteins; D013205:Staphylococcal Protein A; D002772:Cholera Toxin