Next-generation vaccine adjuvants: Integrating nanotechnology, systems immunology, and computational approaches for precision vaccinology

Vaccines based on purified antigens, recombinant proteins, and nucleic acid platforms increasingly depend on adjuvants to induce robust, durable, and appropriately polarized immune responses in humans. While classical adjuvants such as aluminum salts and oil-in-water emulsions have enabled the success of many licensed vaccines, their largely empirical design limits adaptability to emerging pathogens and population-specific needs. This review presents a translational framework for next-generation vaccine adjuvant development by integrating nanotechnology-based delivery systems, innate immune signaling mechanisms, and systems-level computational strategies relevant to human vaccination. We summarize the mechanisms and clinical relevance of licensed and advanced adjuvants, including alum, MF59, AS01/AS04, saponins, toll-like receptor agonists, and lipid nanoparticles, with emphasis on influenza, HPV, herpes zoster, and COVID-19 vaccines. By linking immunological mechanisms with delivery engineering and predictive modeling, this review highlights rational strategies to support safer and more effective human vaccines.