SummaryThe complete genome sequences of more than 60 microbes have been completed in the past decade. Concurrently, a series of new informatics tools, designed to harness this new wealth of information, have been developed. Some of these new tools allow researchers to select regions of microbial genomes that trigger immune responses. These regions, termed epitopes, are ideal components of vaccines. When the new tools are used to search for epitopes, this search is usually coupled with in vitro screening methods; an approach that has been termed computational immunology or immuno-informatics. Researchers are now implementing these combined methods to scan genomic sequences for vaccine components. They are thereby expanding the number of different proteins that can be screened for vaccine development, while narrowing this search to those regions of the proteins that are extremely likely to induce an immune response. As the tools improve, it may soon be feasible to skip over many of the in vitro screening steps, moving directly from genome sequence to vaccine design. The present article reviews the work of several groups engaged in the development of immuno-informatics tools and illustrates the application of these tools to the process of vaccine discovery.
T lymphocytes play a major role in the recognition and subsequent elimination of tumors and intracellular pathogens. Induction of epitope-specific T cell responses can help in the clearance of diseases for which no conventional vaccines exist. However, the lack of simple methods to identify relevant T cell epitopes, the high mutation rate of many pathogens, and HLA polymorphism have made the development of efficient T cell epitope-based, or "epitope-driven" vaccines difficult to achieve. Our research over the past several years has applied bioinformatics tools in conjunction with T cell assays to identify naturally processed putative T cell epitopes from several pathogens. This strategy will accelerate the development of new generation T cell epitope-based vaccines against various pathogens including viruses such as HIV and WNV, bacteria such as M.tb., and parasites such as plasmodium. This chapter will review the use of a bioinformatics-based approach to identify putative T cell epitopes. It will summarize the current state of knowledge regarding T cell-epitope-based vaccines and discuss several ways to improve their efficacy.
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