Structure and Computation in Immunoreagent Design : From Diagnostics to Vaccines

Novel immunological tools for efficient diagnosis and treatment of emerging infections are urgently required. Advances in the diagnostic and vaccine development fields are continuously progressing, with reverse vaccinology and structural vaccinology (SV) methods for antigen identification and structure-based antigen (re)design playing increasingly relevant roles. SV, in particular, is predicted to be the front-runner in the future development of diagnostics and vaccines targeting challenging diseases such as AIDS and cancer. We review state-of-the-art methodologies for structure-based epitope identification and antigen design, with specific applicative examples. We highlight the implications of such methods for the engineering of biomolecules with improved immunological properties, potential diagnostic and/or therapeutic uses, and discuss the perspectives of structure-based rational design for the production of advanced immunoreagents. Immunodiagnostic-based serological tests offer rapid and high-throughput diagnosis of multiple pathogens and can ascertain disease progression.3D structures of protein antigens can be used to predict epitope location using computational biology methods.Computationally designed synthetic epitopes can provide new chemical tools with distinct applications, from diagnosis and patient profiling to therapeutic approaches based on new vaccines.Structure-based antigen design is predicted to deliver future vaccines targeting challenging diseases such as HIV and cancer.As an alternative to nanoparticle epitope presentation systems, structure-based in silico epitope grafting and design methods may be adopted to transplant epitopes onto protein scaffolds to generate antigens that stimulate more potent immune responses.