Title : Immunoinformatics and structural analysis for multi protein vaccine design
Abstract:
To generate more effective subunit vaccines against complex organisms like Leishmania parasites, we need to fuse several immunogenic proteins together. However, the critical issue is that which arrangement of the constituting components should be selected as the favored combination for vaccine design. These days, RNA and protein structure analysis techniques together with immunoinformatics are the handiest approaches available for selecting among the appropriate combinations. To advantage this approach, all possible combinations are designed and analyzed at mRNA and protein levels. At the mRNA level, the full sizes of the transcripts are estimated based on the used expression vector. Then, the secondary structures of mRNAs are predicted by specific web servers. At the protein level, the 3D structures of all combinations are modeled by online platforms. Then, the predicted 3D models are refined and validated by different parameters. Eventually, validated models are superimposed to the original individual proteins to find out structural identity, the higher the similarity the better the reliability of candidate combination. On the other hand, the combined structures are also further analyzed for junctional epitopes by immunoinformatics. This approach was used to combine two immunogenic salivary proteins (PpSP15 from Ph. papatasi and PsSP9 from Ph. sergenti) together to develop an effective vaccine against cutaneous leishmaniasis. The best combination as the vaccine candidate was selected based on mRNA and protein stability results besides peptide analysis and will be presented as an example model for a multi-protein vaccine design.
