The field of systems immunology has emerged as an essential interdisciplinary approach for understanding immune responses on a comprehensive, system-wide level. By integrating high-throughput technologies such as transcriptomics, proteomics, and computational modeling, systems immunology extends beyond traditional research methods. Systems immunology enables researchers to explore the intricate interactions within the immune components and make prediction about vaccine outcomes, accelerating the development of immunizations against pathogens, including rapidly evolving viruses like SARS-CoV-2. The studies in this Research Topic reflects these advancements, offering fresh insights into the molecular and computational aspects of immune system dynamics, which are crucial for improving vaccine efficacy. Our Research Topic has brought together 133 authors worldwide, culminating in 16 articles showcasing cutting-edge research. These contributions cover a range of themes, from immune receptor dynamics and biomarker discovery to computational modeling and predictive analytics in vaccine responses.