Computational Methods in Immunology and Vaccinology: Design and Development of Antibodies and Immunogens

[Image: see text] The design of new biomolecules able to harness immune mechanisms for the treatment of diseases is a prime challenge for computational and simulative approaches. For instance, in recent years, antibodies have emerged as an important class of therapeutics against a spectrum of pathologies. In cancer, immune-inspired approaches are witnessing a surge thanks to a better understanding of tumor-associated antigens and the mechanisms of their engagement or evasion from the human immune system. Here, we provide a summary of the main state-of-the-art computational approaches that are used to design antibodies and antigens, and in parallel, we review key methodologies for epitope identification for both B- and T-cell mediated responses. A special focus is devoted to the description of structure- and physics-based models, privileged over purely sequence-based approaches. We discuss the implications of novel methods in engineering biomolecules with tailored immunological properties for possible therapeutic uses. Finally, we highlight the extraordinary challenges and opportunities presented by the possible integration of structure- and physics-based methods with emerging Artificial Intelligence technologies for the prediction and design of novel antigens, epitopes, and antibodies.