IMMUNOINFORMATICS AND VACCINE DESIGN IN EMERGING VIRAL THREATS

Abstract

 The emergence of new viral threats is always an issue to the health of the world at large and, therefore, we should consider coming out with fast, efficient, and widely protective vaccines against such threats.  The research is based on the entire immunoinformatics methodology and experimental verification of the development of multiepitope vaccines against the most significant viral infections.  Following a mixed-methodology we were organized to predict cytotoxic T lymphocyte (CTL), helper T lymphocyte (HTL) and B-cell epitopes within our selected viral proteomes, and test them in their capacity to hold HLA binding activity, allergic effects as well as being toxic.  Out of 9 groups of viral candidates, 180 high-confidence epitopes were identified. Over 80 percent of them were not allergic or toxic and capable of an immense binding affinity (IC50 er 200 nM) over an assortment of HLA polymorphisms.  We prepared the multi-epitope constructs and validated these constructs. They were stably folded and had a nice interaction with Toll-like receptors (TLR2, TLR4).  Both Molecular docking and MM/GBSA energy facilitated in proving that the receptor was stable and that it exhibited low values of binding free energy, an indication that the receptor had the potential of strongly activating the immune system.  In immune simulations, high cytokine levels, an increase of memory T and B cells, and persistence of immunoglobulin responses were witnessed following simulated boost doses.  The test ranged that in vivo ELISpot estimation and flow cytometry experiments indicated that highly-ranked epitopes exposed T cells and made them secrete IFN-gamma.  These findings demonstrate the accuracy of the immunoinformatics platforms in the prediction of illnesses and indicate the extent to which they can be useful in accelerating the development of epitope-based vaccines.  The work provides us with a paradigm on how to rapidly make vaccines which would be used in future to deal with new viruses and pathogens which are spreading.  The present study contributes to the area of next-generation vaccinology, based on the combination of in silico work with an experimental validation. It also provides valuable insight on how to prepare to a pandemic.