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Gene Therapy for the prevention of Malaria
M. Zheng, S. Cunningham, G. Logan and I. Alexander in collaboration with R. Coppel
Malaria affects 400-500 million people and kills 2-3 million people annually, in particular women and children. With the emergence of malarial strains resistant to current drug therapies, and an increasing incidence in the prevalence of pesticide-resistant mosquito vectors, there is an urgent need to develop vaccines that can provide protection from this parasite.
With this goal in mind, we are collaborating with Professor Ross Coppel (Department of Microbiology, Monash University, Melbourne, Australia) to develop genetic vaccines that might provide immunity to the malarial parasite. These vaccines differ from conventional vaccines in that genetic material derived from the pathogen, rather than live or killed forms of the infectious organism, are injected into the host. Cells that take up this genetic material can synthesise proteins normally found in the pathogen in such a manner that the ensuing immune response to these pathogen-associated proteins will confer protection to the infectious agent.
This project is specifically designed to investigate the utilisation of adenovirus-associated vectors (AAV) to deliver such genetic vaccines. AAV is advantageous over other virus vectors in its capacity to both transduce muscle cells with high efficiency and produce long-term expression of vector-encoded transgene in this tissue. We have shown that injection of AAV encoding malarial antigens into the muscles of mice produces an immune response where antibodies specific for the malarial antigens are synthesised. We are currently in the process of optimising the delivery of this vector and are considering a number of 'genetic adjuvants' that may be incorporated into the system that will increase the potency of this vaccine to further raise the level of malarial-specific serum antibodies. Upon optimisation of this vector, the efficacy of the AAV vaccine can be tested in the laboratory of Professor Coppel, which has developed a malarial mouse model for this purpose.
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