Discovery of conserved epitopes through sequence variability analyses

Sequence variation is a common theme used by a variety of human pathogens, including the Human Immunodeficiency Virus (HIV-1), to escape the host immune response. Therefore, under such scenario, a successful vaccine should be based on antigenic determinants lying within conserved protein antigen regions. This chapter will illustrate the application of sequence variability analyses to the identification of such conserved regions and/or epitopes using the Protein Variability Server (PVS). PVS is a web-based tool that compute the absolute site variability in protein antigens from the relevant multiple protein-sequence alignments (MSAs). In addition, PVS has been tuned to facilitate the design of epitope-based vaccines. Specifically, PVS enables the prediction of conserved T cell epitopes by generating a variability-masked sequence that can be submitted to the RANKPEP T cell epitope prediction tool. Moreover, PVS allows the identification of conserved fragments that are surface exposed and thus potential targets of the humoral response.

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