Malaria Vaccine - Vaccine Development Strategies For The Future

Vaccine Development Strategies For The Future

The development of a vaccine of therapeutic and protective benefit against the malaria parasite requires a novel approach as to date there are no vaccines available that effectively target a parasitic infection. The focus so far has been predominately on the use of sub-unit vaccines. The use of live, inactivated or attenuated whole parasites is not feasible and therefore antigenic particles, or subunits, from the parasite are isolated and tested for immunogenicity i.e. the ability to elicit an immune response. The majority of subunits tested have been discussed above and are frequently combined with adjuvants and specialised delivery systems to increase the very variable level of immune response. The most recent advances in the field of sub-unit vaccine development include the use of DNA vaccination. This approach involves removing sections of DNA from the parasitic genome and inserting the sequences into a vector, examples including plasmid genomes, attenuated DNA viral genomes, liposomes or proteoliposes, and other carrier complex molecules. When inoculated the plasmid or attenuated virus is endocytosed into a host cell, the DNA sequence is then incorporated into the host DNA and replicated by protein synthesis. The proteins then produced are expressed on the cell surface membrane of the ‘infected’ cell. These bind to the HLA molecules, priming T cells and therefore creating a population of memory T cells specific to the inoculated DNA sub-unit. This technique has been shown to produce a high rate of T cell response but poor level of antibody production. The efficacy of DNA vaccines can be assessed using an ELISPOT assay. The development of this method of testing for immune responses is extremely beneficial when examining the potential efficacy of a vaccine candidate and is hoped to enable critical analysis of the mechanisms that provide ‘partial’ protection, thus facilitating a greater understanding of vaccine technology. This approach of potentially allowing the modification of vaccine candidates to improve development techniques and further scientific understanding is known as ‘iterative development’. The advantage of DNA vaccines over classical attenuated vaccines are numerous and include being able to mimic MHC class 1 CD8+ T cell specific responses that potentially could reduce some of the safety concerns associated with vaccine therapy and additionally provide a substantial reduction in production cost and due to the nature of DNA vaccines, increased ease of storage.