This project is concerned with the potential development of new and improved vaccines against diarrhoeal diseases caused by V. cholerae and enterotoxigenic E. coli. In addition, the project is also concerned with the development of a single dose vaccine against B. pertussis. Recombinant antigens or antigens isolated from the relevant microorganisms will be entrapped in microparticles prepared from the poly(lactide-co-glycolide) polymers. After assessment of the structural integrity and antigenicity of the entrapped antigens, the rate of release of antigens from microparticles will be assessed in vitro. Those microparticles with the desired controlled release properties will then be assessed in small animal models to determine the immunogenicity of entrapped antigens. Microparticles which show encouraging responses in vivo, will undergo extensive in vitro characterisation using a number of physicochemical techniques to define as closely as possible the parameters promoting the induction of potent immune responses. In vivo studies will include studies designed to assess the level of protection induced in animal models by microparticulate vaccines. Selected candidate vaccines will also be assessed in non-human primates to confirm the observations from small animal models.
To enhance the efficacy of microparticles as oral vaccines,
targeting ligands will be conjugated to their surface to promote the uptake of particles from the gut. Prospective targeting ligands will include cholera toxin B subunit and lectins, these agents will be conjugated to the surface of microparticles using novel techniques
developed through a previous E.C. funded research programme co-ordinated from Nottingham.
Funding SchemeCSC - Cost-sharing contracts
EN6 3QG Potters Bar
110067 New Delhi
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