Our work at MIVAC is structured around 4 major research themes. These themes are representing different scientific approaches to understanding the complexity and control of the mucosal membranes and their functions. Some projects are limited to a particular theme, whereas others are cross-sectional and multifacetted, employing the expertise of e.g. immunologists, glycobiologists and clinical gastroeneterologists. Together with the industrial partners the MIVAC themes constitute a powerful tool for future successful research in Göteborg.
See our complete list of resarch projects at MIVAC.
1. Mucosal barrier functions and innate immunity
2. Immunomodulation and adjuvants
3. Immunoregulation of IgA immunity versus Tolerance
4. Development and preclinical and clinical testing
Mucosal barrier functions and innate immunity
The gastrointestinal tract is protected by a sophisticated system that can be traced back to the first organisms with a gut. This includes several lines of defense, where an efficient system for trapping and removal of microorganisms make up a major first line of defense. A mucus gel layer covers the epithelial cells and provides a first site for trapping infectious agents; this is accomplished by both trapping microorganisms in the gel and by elaborating specific glycans to which different microbes bind. An important focus at MIVAC is research in mucin and glycan biology, with studies ranging from molecular mechanisms of the intracellular glycosylation machinery to the role of mucins in disease susceptibility.
The epithelial cell is a central part of the barrier function. Macromolecular transport in epithelial cells is an integral part of the mucosal immune system. It is critical for our understanding of homeostasis and host interaction with the commensal flora, for recognition of pathogenic bacteria and viruses, and for the specific targeting of engineered bacterial vaccine delivery vehicles. In this area, MIVAC researchers are studying the role of epithelial cells in mucosal barrier function, especially in relation to the development of inflammatory responses.
MIVAC scientists are also leading in the area of integrative secretomotor physiology. In the intestine, there is an important sophisticated secretomotor program generated and coordinated by the enteric nervous system that regulates the degree of contact between the luminal phase and the mucosal membrane. Dysfunction of this system rapidly leads to intestinal bacterial overgrowth of the small intestine.
Immunomodulation and adjuvants.
Recent studies have demonstrated intricate interactions between the innate and adaptive immune systems at mucosal membranes. Dendritic cells (DC), for example, have been shown to sample antigens from the lumen. Upon antigen-exposure in the mucosal tissues, DC then undergo maturation and migrate to regional lymph nodes for antigen presentation to T cells in the context of MHC class I or II.
Immunoregulation of IgA immunity versus Tolerance
The induction of tolerance is critical to mucosal homeostasis. Several mechanisms are thought to be responsible for mucosal tolerance. Of these, the generation of regulatory T cells is considered most important, but also other cell types - including NKT cells - can control aggressive immune responses. MIVAC members have a long-standing interest in understanding the mechanisms for tolerance induction and mucosal immunoregulation. The pursued research includes studies of mechanisms for induction of tolerance or its failure in health and disease, as well as elaborating strategies for more efficient tolerance induction in order to modulate different autoimmune diseases and chronic inflammatory conditions.
A fundamental characteristic of the mucosal membrane is the production of secretory IgA. MIVAC researchers have contributed significantly to the understanding of what role and requirements are needed for IgA production in the lamina propria of the mucosa. Since better understanding of this process is essential for the development of future vaccines, studies of IgA B-cell differentiation are currently being conducted.
Development and pre-clinical and clinical testing
MIVAC researchers have a unique experience and track record of having taken a specific vaccine, the oral cholera vaccine, from basic research to a final vaccine product (Dukoral®), which is now widely registered and marketed. Therefore, MIVAC has access to important facilities, skills and technologies for monitoring vaccine development and testing such as (i) defining the molecular mechanisms of disease and immunity in mucosal infections; (ii) identifying candidate protective antigens for inclusion in vaccines; (iii) developing methods for conventional or recombinant vaccine production from lab scale up to industrial scale; (iv) developing facilities and resources for all stages of preclinical and clinical (from phase 1 to phase 3 “field trial efficacy” ) testing of vaccines; (v) acquiring expertise in product registration and (vi) introducing vaccines in the private and public health sectors.
To aid this work, MIVAC has good connections with the clinic, especially the department of gastroenterology at Sahlgrenska University Hospital.
The MIVAC groups are currently being involved in early discovery and/or more advanced development and testing of a number of important vaccines against:
Gastrointestinal infections: E. coli (ETEC) diarrhea, O139 Vibrio cholerae, Helicobacter pylori, and Salmonella.
Respiratory infections: Pneumococcal, B. pertussis, Influenza virus and Tuberculosis, Hemophilus influenzae and Streptococcus group B.
Genital-rectal infections: Hemophilus ducreyi (chancroid), Chlamydia trachomatis, Herpes type 2 virus, and HIV/AIDS.