The CTA1-DD vaccine adjuvant binds to human B cells and potentiates their T cell stimulating ability.
The present study demonstrates that the novel CTA1-DD-adjuvant, which combines the full enzymatic activity of the A1 subunit of cholera toxin (CT) with an immunoglobulin-binding domain of Staphylococcus aureus protein A (SpA), binds directly to human peripheral blood B lymphocytes of all classes and greatly augments B cell functions in vitro. These effects were reflected in strongly enhanced co-stimulation, resulting in augmented T cell responses to polyclonal-specific as well as Ag-specific activation in vitro. The CTA1-DD-adjuvant had pronounced effects on B cell functions with up-regulated expression of several important activation and co-stimulatory molecules, in particular CD86. Moreover, the adjuvant alone promoted cytokine and chemokine secretion by targeted B cells and in the presence of additional stimuli proliferative responses were augmented. These effects were dependent on the whole enzymatically active CTA1-DD molecule, since DD alone had no effects on the B cells. Collectively our data suggest that CTA1-DD acted via enhanced co-stimulation, which holds promise as to the use of CTA1-DD as a non-toxic adjuvant in future vaccines for human use.
Eriksson
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A
Department of Clinical Immunology, University of Göteborg, S-413 46, Göteborg, Sweden.
Lycke
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N
D000276:Adjuvants, Immunologic / Q000493:pharmacokinetics* / Q000494:pharmacology*; D015703:Antigens, CD / Q000276:immunology; D001402:B-Lymphocytes / Q000187:drug effects* / Q000276:immunology; D051940:B7-2 Antigen; D002455:Cell Division / Q000187:drug effects; D002772:Cholera Toxin / Q000493:pharmacokinetics* / Q000494:pharmacology*; D016207:Cytokines / Q000096:biosynthesis; D006801:Humans; D066298:In Vitro Techniques; D015759:Ionomycin / Q000494:pharmacology; D007959:Lymphocyte Culture Test, Mixed; D008562:Membrane Glycoproteins / Q000276:immunology; D010641:Phenotype; D011993:Recombinant Fusion Proteins / Q000493:pharmacokinetics* / Q000494:pharmacology*; D013205:Staphylococcal Protein A / Q000378:metabolism; D013601:T-Lymphocytes / Q000276:immunology*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
D000276:Adjuvants, Immunologic; D015703:Antigens, CD; D051940:B7-2 Antigen; C497964:CD86 protein, human; C440610:CTA1-DD protein, recombinant; D016207:Cytokines; D008562:Membrane Glycoproteins; D011993:Recombinant Fusion Proteins; D013205:Staphylococcal Protein A; D015759:Ionomycin; D002772:Cholera Toxin; D013755:Tetradecanoylphorbol Acetate