Artificial Intelligence and Machine Learning in the Development of Vaccines and Immunotherapeutics Yesterday, Today, and Tomorrow

The development of vaccines and immunotherapies against infectious diseases and cancers has been one of the major achievements of medical science in the last century. Subunit vaccines offer key advantages over whole-inactivated or attenuated-pathogen-based vaccines, as they elicit more specific Band T-cell responses with improved safety. However, developing subunit vaccines is often cost and timeconsuming and may not predict fast, strong, and long-lasting immunity, limiting their ability to rapidly counter apparent growing emerging pandemics and cancers. In the past, the development of vaccines and immunotherapeutics relied heavily on trial-and-error experimentation and extensive in vivo testing, often requiring years of pre-clinical and clinical trials. Today, artificial intelligence (AI) and deep learning (DL) are actively transforming vaccine and immunotherapeutic design, by (i) offering predictive frameworks that support rapid, data-driven decision-making; (ii) increasingly being implemented as time-and resourceefficient strategies that integrate computational models; systems vaccinology and multi-omics data to better phenotype, differentiate, and classify patients diseases and cancers; predict patients' immune responses and identify the factors contributing to optimal vaccine and immunotherapeutic protective efficacy; (iii) refining the selection of Band T-cell antigen/epitope targets to enhance efficacy and durability of immune protection; and (iv) enabling a deeper understanding of immune regulation, immune evasion, immune checkpoints, and regulatory pathways. The future of AI and DL points toward (i) replacing animal preclinical testing of drugs, vaccines, and immunotherapeutics with computational-based models, as recently proposed by the United States FDA; and (ii) enabling real-time in vivo modeling for immunobridging and prediction of protection in clinical trials. This may result in a fast and transformative shift for the development of personal vaccines and immunotherapeutics against infectious pathogens and cancers.