We have pioneered the development of cholera toxin (CT) derived immmunomodulators and have acquired patents for a family of unique mucosal modulators and adjuvants, based on the CTA1-DD gene fusion protein. This molecule capitalizes on the ADP-ribosylating function of the CT A1-subunit, which is expressed together with a dimer of fragment D from the Staph. aureus proteinA. The CTA1-DD has been found to target cells of the innate immune system with little reactogenic effect on the site of injection or administration. Thus, the CTA1-DD is a non-toxic enzyme-dependent highly efficacious adjuvant system for a wide range of immune responses including priming of CD4 T cells, CTL and antibody responses. Enzymatically inactive mutants on the other hand are effective inducers of antigen-specific T cell tolerance and are currently exploited in various anti-inflammatory treatments. Moreover, we have developed novel formulations which incorporate CTA1-DD into immune stimulating complexes (ISCOMs). These adjuvant vectors have been found highly effective for a large number of candidate vaccines and currently feasibility studies with influenza virus, rota virus, tuberculosis, Helicobacter pylori and HIV-vaccines are ongoing. Clinical trials with the CTA1-DD adjuvant are planned for 2007 and GMP-material should be available by late 2006.
Other areas of intense research in the group include basic studies of IgA B cell development in the gastro-intestinal tract, female genital tract T-cell immunity and infections caused by Chlamydia trachomatis, or gastric infections with Helicobacter pylori and important role of CD4 effector T cells in the afflicted gastric mucosa.
Eriksson A, Schön K and Lycke N. (2004). The Cholera Toxin-Derived CTA1-DD Vaccine Adjuvant Administered Intranasally Does Not Cause Inflammation or Accumulate in the Nervous Tissues. J. Immunol. 173: 3310-3319
Akhiani A, Stensson A, Schön K and Lycke N. (2005). IgA antibodies impair resistance against Helicobacter pylori infection; studies on immune evasion in IL-10 deficient mice. J. Immunol., 174:8144-8153, 2005
Grdic D, Ekman L, Schön K, Lindgren K, Mattsson J, Magnusson K-E, Ricciardi-Castagnoli P and Lycke N. (2005). Splenic marginal zone dendritic cells mediate the cholera toxin adjuvant effect: dependence on the ADP-ribosyl transferase activity oth the holotoxin. J. Immunol., 175: 5192-5202
Helgeby A, Robson N, Donachie A, Beackock-Scharp H, Lövgren K, Mowat A and Lycke N. (2006). The combined CTA1-DD/ISCOM adjuvant vector promotes priming of mucosal and systemic immunity to incorporated antigens by specific targeting of B cells. J Immunol. 176:3697-3706.