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Commercial Success of ECLAIR Programme
AGRE-0008: The use of F17 and CS31A fimbriae as carriers for viral epitopes and their applications as vaccines |
AGRE-0008: The use of F17 and CS31A fimbriae as carriers for viral epitopes and their applications as vaccines
Science Background
Some bacteria produce proteinaceous appendages (fimbriae or capsular proteins) that cover their surface. These are made up of a large number of associated protein subunits. Such fimbriae and capsular proteins (F17 and CS31A respectively) were isolated from pathogenic strains of Escherichia coli that may infect cattle. Using genetic engineering techniques it was possible to modify the amino acid sequences of these proteins. Such modified surface proteins could then be produced and expressed in large quantities on the surface of the bacteria. Following identification of the required epitope (the minimal antigenic material eliciting protective antibodies), this should enable the production of vaccines based on heterologous constructs using the surface proteins as carriers for the epitope.
Objectives
This project aimed to use the F17-A and CS31A subunits as carrier proteins for the introduction of epitopes identified on bovine rotavirus strains and on porcine transmissible gastroenteritis virus (TGEV) and to use these constructs as vaccines. Both viruses are responsible for diarrhoea with high economic losses in farm animals.
Significant changes and results since end of ECLAIR
The coordinators of this project, INRA (Ceyrat, France) obtained a French patent (1995 No. 9215464), extended to Europe and the USA, covering the procedures for obtaining and use of a unit of a CS31A capsular protein modified by at least one heterologous peptide, a CS31A capsular protein and microorganisms carrying these units. Research was continued by INRA who, following trials in 1998/9, are in discussion with a French company regarding development of a vaccine based on this technology. Since, the results of this work form the basis of a current patent application further details are not given here.
Results
At end of this ECLAIR project
Several viral epitopes with potential vaccinating properties were identified and the mechanism was established. Results obtained in pigs against TGEV were not satisfactory, hence further studies were required. Although vaccine protection was not demonstrated, results were regarded as promising enough to justify carrying out further studies.
Current position
Since the project was completed, it was realized that the target of the potentially commercial vaccine (against TGEV) was not of economic importance in Europe. This was because a naturally occurring respiratory coronavirus now spreads among pig herds and induces cross protection against TGEV. Consequently, a commercial vaccine is not now required to control this disease. Further research was carried out in the Laboratoire de Microbiologie, INRA, Clermont-Ferrand. Work did not continue in the Belgium laboratories that were associated with the initial project since the leader of the Belgian group left the research institute and moved to a commercial vaccine company.
A French project, that is still ongoing, was initiated in 1995 as part of a post-graduate programme supported by INRA and the Regional Council (Région Auvergne). A thesis resulting from this work was evaluated in March 1999. This research investigated the use of the CS31A fimbrial system as a carrier for the thermostable enterotoxin from a bacterium that is a causative agent for diarrhoeal diseases that infect calves and piglets and may also infect tourists. A peptide has been identified that is not immunogenic in its native form but induces protective antibodies when associated with a carrier protein. The carrier protein used was CS31A, with the construct based on the methods and concepts developed in the course of the ECLAIR research.
Various hybrid proteins produced by recombinant bacteria were found to induce the required antibodies in rabbits. In a mouse model, one of these hybrid proteins elicited antibodies that neutralized the biological activity of the specific enterotoxin under investigation. Cows vaccinated during November 1998 with these recombinant bacteria are being studied to establish whether they produce antibodies that neutralize the biological activity of the enterotoxin. Positive results from this work could be the starting point for the development of a commercial vaccine for use with pigs or cattle. It could also be of value as a prophylactic or therapeutic treatment of humans at risk of traveller’s diarrhoea.
Impact
Commercial
There is a possibility of collaboration between INRA and a commercial company that supplied INRA with adjuvant for vaccination of the cows. This will depend on the results of the vaccination trials. As indicated above, patent considerations limit disclosure of detailed information at the time of writing this report.
Associated
This project did not lead directly to commercial products. However, the project stimulated further academic studies that have led to the possibility of the commercial development indicated above.
Further Information
Some of the results from the recent post-graduate studies have been submitted for publication in the journal Molecular Microbiology (in press 1999).
Contacts
Author
INRA
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