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  • br Proteases with special focus on cysteine proteases br

    2020-02-13


    Proteases with special focus on cysteine proteases
    Vaccination using cysteine proteases as antigens with special emphasis on DNA-vaccines
    Concluding remarks In spite of the great potential of DNA vaccines, the technology has not been as revolutionary as expected in higher mammals. In fish, on the other hand, some DNA immunizations have demonstrated to be highly efficient [4]. Injection of nanogram levels of plasmids with antigen inserts have shown complete protection against two rhabdoviruses in salmonids even when these were administered without any adjuvants. In the main part of these fish neutralizing Tianeptine sodium were found [66]. Fish have a more diversified innate immune system compared to mammals [127] and even though the fish do not possess the same advanced adaptive immune system and the same classes of antibodies as mammals do they can respond with a highly specific immunity [4], [66]. Therefore it is relevant to investigate fish immune responses against these vaccines and to use this model system for the possible development of antiparasitic piscine DNA vaccines, including cysteine proteases as vaccine candidates. The model system in fish may also be of use in the development of antiparasitic DNA vaccines in mammals corresponding to the use of zebrafish in the study of neurological diseases and drug screenings [128], [129]. It is important to find the best qualified parasitic antigens with high immunogenicity as vaccine candidates. Primarily, surface antigens have been investigated but proteases have high potential. Proteases are of critical importance and are involved in a number of functions during the parasitic life cycle including infection and evasion of the host immune defence. In some instances, proteases are able to direct the immune system of the host towards a Th1 or a Th2 response, which augments survival of the parasites within the hosts. Due to the fact that DNA vaccines can be very successful in fish and due to the possibility of cysteine proteases being immunogenic we are investigating whether two cysteine proteases (ICP1 and ICP2) from I. multifiliis can have the potential to be DNA vaccine candidates in rainbow trout. Further research into proteases and DNA vaccinations might open up new doors, in order to create effective vaccines against parasitoses.
    Acknowledgments This study was performed under the FP6 project IMAQUANIM funded by the EU-commission and by the Danish Fish Immunology Research Centre and Network www.dafinet.dk.
    Introduction The gastrointestinal tract is the largest organ of the immune system and is under constant exposure to an array of exogenous antigens, such as ingested food proteins and commensal bacteria [1]. Upon ingestion, dietary proteins undergo enzymatic hydrolysis in the harsh acidic environment of the stomach. A single epithelial cell layer separates this potential antigenic load from lymphocytes, antigen-presenting cells, and other immune cells of the lamina propria that together constitute the mucosa-associated lymphoid tissue (MALT) [2]. The proper function of this epithelial barrier is dependent on the intactness of the apical plasma membrane of epithelial cells, as well as on the intercellular tight junctions (TJs). TJs are macromolecular protein assemblies composed of integral membrane proteins (claudins, occludin, tricellulins, and junctional adhesion molecules), cytoplasmic cytoskeletal linker proteins zonula occludens (ZO)-1, ZO-2, and ZO-3, and associated signaling molecules and cell cycle regulators [3]. The disruption of intestinal epithelium tight junctions can cause increased permeability, which enables normally excluded molecules to cross the mucosal epithelium by paracellular permeation. This, in turn may cause inflammatory conditions in the intestinal mucosa such as Crohn\'s disease, celiac disease, inflammatory bowel disease, acute pancreatitis, and food allergy [4].