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.