Immunomodulation at mucosal surfaces
The induction of immunologic tolerance is critical to mucosal homeostasis. Natural tolerance is acquired by gut processing of antigens. To understand the regulatory control that governs the outcome of mucosal exposure to vaccines, we need to advance our knowledge about the two main response patterns: tolerance or active IgA immunity. In fact, in the absence of an immunoenhancer/adjuvant, immune tolerance rather than immunity is the most likely outcome. This can be used clinically, as mucosal vaccines to treat autoimmune diseases have been proposed and attempts to therapeutically prevent rheumatoid arthritis and type I diabetes, for example, have been made. On the other hand, when a strong adjuvant is used, protective immunity against pathogenic microorganisms may be generated. This latter strategy is the hallmark of mucosal vaccination in general and a special strength of MIVAC in particular.
We are currently studying specific targeting of vaccine adjuvants to cells of the innate immune system as a strategy for reducing side effects and improving efficacy. In particular, we are exploring the ADP-ribosylating non-toxic CTA1-DD adjuvant and the membrane-targeted CpG-CTB adjuvant. Members of MIVAC are pioneers in this field of research and are international leaders in toxin adjuvant research. MIVAC is also exploring the tolerance strategy in order to treat autoimmune diseases and promising data, including early proof-of-principle data in humans, has already been generated regarding the use of CTB-conjugates or mutant, enzymatically inactive, CTA1R7K-DD, for induction of tolerance against autoimmune disease. This research will have substantial impact on vaccine design and development and will have great implications for finding new treatments against autoimmune disease, or allergy, in addition to promoting the development of successful mucosal vacines.
Postdocs involved in the project: Frida Jacobsson, Dominique Frailery and Anna Holmberg.