The B-cell targeted CTA1-DD vaccine adjuvant is highly effective at enhancing antibody as well as CTL responses.
A novel immunomodulating gene-fusion protein, CTA1-DD, has been developed which 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 is non-toxic and greatly augmented T-cell-dependent and T-cell-independent responses to soluble admixed antigens after systemic as well as mucosal immunizations. CTL and antibody responses of all classes were increased by 10- to 100-fold above those observed in control mice immunized without adjuvant. CTA1-DD does not appear to form immune complexes or bind to soluble Ig following injection, but rather it binds directly to B-cells of all isotypes, including naïve IgD+ cells. No binding was observed to macrophages or dendritic cells, and immunizations in Fc gamma R-deficient mice demonstrated unaltered enhancing effects. As shown by inactive mutants, the CTA1-DD adjuvant is dependent on ADP-ribosyltransferase activity and requires the binding to Ig- via the DD moiety. The enhancing effect is associated with enlarged germinal centers, and binding of CTA1-DD to the B-cells strongly upregulates co-stimulatory molecules and counteracts apoptosis by inducing intracellular Bcl-2.
Department of Clinical Immunology, University of Göteborg, S-413 46 Göteborg, Sweden. nils.lycke@microbio.gu.se
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D000276:Adjuvants, Immunologic / Q000008:administration & dosage* / Q000633:toxicity; D000818:Animals; D000917:Antibody Formation; D000938:Antigen-Presenting Cells / Q000187:drug effects / Q000276:immunology; D001402:B-Lymphocytes / Q000187:drug effects / Q000276:immunology; D002490:Central Nervous System / Q000276:immunology / Q000378:metabolism; D002772:Cholera Toxin / Q000008:administration & dosage / Q000276:immunology* / Q000633:toxicity; D005818:Genetic Engineering; D015395:Histocompatibility Antigens Class I / Q000378:metabolism; D006801:Humans; D018928:Immunity, Mucosal; D051379:Mice; D009154:Mutation; D011065:Poly(ADP-ribose) Polymerases / Q000378:metabolism; D013205:Staphylococcal Protein A / Q000008:administration & dosage / Q000276:immunology* / Q000633:toxicity; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D014612:Vaccines / Q000008:administration & dosage*
D000276:Adjuvants, Immunologic; D015395:Histocompatibility Antigens Class I; D013205:Staphylococcal Protein A; D014612:Vaccines; D002772:Cholera Toxin; D011065:Poly(ADP-ribose) Polymerases