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A consortium of scientists based the University of Edinburgh, the Moredun Research Institute and the Scottish Agricultural College working in partnership with Novartis Animal Vaccines Limited propose a three year LINK research programme that has two related aims. The first is to develop an effective and inexpensive vaccine to limit EHEC colonisation of cattle and therefore reduce the threat to human health from this pathogen. The second is to develop systems for delivery of antigens to gastrointestinal follicle-associated epithelium in order to generate appropriate mucosal responses.
The two aims are intrinsically linked as the antigens to be trialled in the vaccines are likely also to target FAE and will be tested to compare intra-muscular injection with mucosal delivery. <P>
This research builds on five years of research into EHEC colonisation of cattle by the research consortium and two years of investment by NAVL into adhesins expressed by EHEC O157:H7. The current identified antigens are the Loc8 fimbrial adhesin, the H7 flagellin and EspA type III translocation filaments. These will be tested alone and in combination.<P>
The research will exploit well developed in vivo and in vitro systems to investigate the interaction of EHEC O157:H7 with the bovine host including a colonisation protocol for calves developed by the grouping that has led to the identification of the terminal rectum as the principal site of colonisation of cattle by EHEC O157:H7. This protocol is being applied to test direct antimicrobial interventions by our grouping. The research combines the expertise of scientists in immunology, FAE biology, animal infectious diseases, vaccine development and molecular biology with excellent microbiology laboratories and large animal containment facilities.
Objective:
<OL> <LI> To characterise the development of protective immunity in cattle to E. coli O157:H7 colonisation.
<LI> To test purified Loc8 fimbriae, H7 flagella and EspA filaments alone and in combination as vaccines in cattle.
<LI> To develop mucosal delivery systems with the identified antigens and compare the immunogenicity of these with systemic delivery.