Objective
A major goal in vaccine development is the design of heat-stable, non-parenteral vaccines which simplify vaccine delivery, yet safely and effectively stimulate the principle protective immune responses against pathogens transmitted across mucosal and cutaneous tissues. The development of such "second generation vaccines" represents a priority target for the IVth Framework of the EC and requires the development of innovative technology and generic systems which can be used against a broad spectrum of diseases. The overall aim of this proposal is to exploit advances in recombinant DNA technology and the well defined genetics of the spore-forming bacterium Bacillus subtilis to develop spores as a generic system for the development of such "second generation vaccines".
B. subtilis spores offer a number of unique features making them particularly suitable as a generic vaccine vehicle: 1. Non-pathogenic 2. Dormant with suitable storage and desiccation properties 3. Suitable for non-parenteral delivery, particularly by the oral and nasal route 4. Ubiquitous with no evidence for compromised immune status in man 5. Ease of genetic modification 6. Produced in large quantities; safely, efficiently and cost effectively 7. Robust and suitable for field use, particularly in the developing world
In preliminary work we have begun to develop spores as a tool for heterologous antigen presentation and shown that spores are immunogenic since administration of non-recombinant spores by the oral or intranasal route elicits spore-specific serum IgG and secretory IgA (SIgA) in the rectum and vagina. In addition, we have been able to stably express an SIV antigen (gag p27) on the spore surface demonstrating the potential of spores for delivering antigens to target the immune response.
SPECIFIC OBJECTIVES
Our initial experiments have demonstrated the potential of using non-pathogenic B. subtilis spores for generic vaccine development. Here, 5 major European laboratories with considerable experience in either Bacillus genetics, mucosal immunity and in vaccine development will combine their expertise to fully demonstrate and validate the use of spores as a vaccine vehicle. Our goals are to optimise antigen presentation using spores and fully characterise the systemic and mucosal immune responses following oral or intranasal delivery of recombinant spores. We have chosen two model antigens (i) the capsid protein of Simian Immunodeficiency virus (SIV gag p27) and, (ii) tetanus toxoid fragment C ( ITFC). Both are candidate proteins for inclusion in a vaccine against two important pathogens for which we have the relevant animal models and expertise in place to address efficacy. Our work plan will follow 8 distinct work packages as outlined below.
WP 1 and 2: Construction and characterization of recombinant spores: WP 3: Parenteral immunization of mice with recombinant spores to determine the immunogenicity of the gag p27 or TTFC proteins. WP 4: Evaluation of immune responses following mucosal immunization with recombinant spores:
WP 5: Challenge studies: for animals immunized with spores expressing TTFC.
WP 6: Development of spores as a delivery vehicle for a mucosal adjuvant.
WP 7: Dissemination and persistence of recombinant spores. WP 8: Development of non-viable spores.
Fields of science (EuroSciVoc)
CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques.
CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques.
- medical and health sciencesbasic medicineimmunologyimmunisation
- natural sciencesbiological sciencesmicrobiologyvirology
- medical and health sciencesmedical biotechnologygenetic engineering
- natural sciencesbiological sciencesbiochemistrybiomoleculesproteins
- medical and health sciencesbasic medicinepharmacology and pharmacypharmaceutical drugsvaccines
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Topic(s)
Call for proposal
Data not availableFunding Scheme
CSC - Cost-sharing contractsCoordinator
TW20 0EX EGHAM,SURREY
United Kingdom