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Regulation of innate and adaptive immunity at mucosal membranes-implications for cholera toxin derived vaccine adjuvant design.

Nils Lycke

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We have pioneered the development of cholera toxin (CT) derived immmunomodulators and have acquired Nils Lyckepatents 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.

 

Sidansvarig: Dan Baeckström|Sidan uppdaterades: 2016-09-19
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