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The selection in silico of vaccine candidates by Reverse Vaccinology can be challenged by: sequence variability of the pathogens, the immune evasion strategies adopted by the pathogens, the low abundance of surface antigens and eventually their low stability once expressed as recombinant antigens. These challenges can be faced with a deep knowledge of the three-dimensional structure of the candidates. The advances in cryo-EM together with well-set X-ray crystallography and HDx-MS allowed recently the structural characterization of a huge amount of new proteins. The use of 3D protein structures similarity is a key tool in the highly specific antigen identification. We generate and compare 3D protein structure by the Structure Similarity Algorithm GEMINI running in a dedicated freely available GSK repository that contains internally generated structures as well as publicly available structure related databases and literature data.
