The CTA1-DD vaccine adjuvant binds to human B cells and potentiates their T cell stimulating ability

• Published in: Vaccine Vol. 22; no. 2; pp. 185 - 193
• Main Authors: Eriksson, A, Lycke, N
• Format: Journal Article
• Language: English
• Published: Oxford Elsevier Ltd 12-12-2003; Elsevier; Elsevier Limited
• Subjects: Adjuvants, Immunologic - pharmacokinetics; Adjuvants, Immunologic - pharmacology; Antigens, CD - immunology; Applied microbiology; B-Lymphocytes - drug effects; B-Lymphocytes - immunology; B7-2 Antigen; Bells palsy; Biological and medical sciences; Blood; Cell Division - drug effects; Cholera toxin; Cholera Toxin - pharmacokinetics; Cholera Toxin - pharmacology; Clinical trials; Cytokines - biosynthesis; Enzymatic activity; Enzymes; Fundamental and applied biological sciences. Psychology; Human B cells; Humans; Immune system; Immunomodulation; In Vitro Techniques; Influenza; Ionomycin - pharmacology; Lymphocyte Culture Test, Mixed; Lymphocytes; Membrane Glycoproteins - immunology; Microbiology; Phenotype; protein A; Proteins; Recombinant Fusion Proteins - pharmacokinetics; Recombinant Fusion Proteins - pharmacology; Staphylococcal Protein A - metabolism; Staphylococcus aureus; T-Lymphocytes - immunology; Targeted adjuvants; Tetradecanoylphorbol Acetate - pharmacology; Toxicity; Toxins; Vaccines; Vaccines, antisera, therapeutical immunoglobulins and monoclonal antibodies (general aspects); Waterborne diseases; Targeted adjuvants; Cholera toxin; Human B cells; Immunomodulation; Human; B-Lymphocyte; Vaccine; Immunostimulation; Immunological adjuvant; T-Lymphocyte
• ISSN: 0264-410X; 1873-2518
• DOI: 10.1016/S0264-410X(03)00567-X

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.