Transforming vaccinology.

The COVID-19 pandemic placed the field of vaccinology squarely at the center of global consciousness, emphasizing the vital role of vaccines as transformative public health tools. The impact of vaccines was recently acknowledged by the award of the 2023 Nobel Prize in Physiology or Medicine to Katalin Kariko and Drew Weissman for their seminal contributions to the development of mRNA vaccines. Here, we provide a historic perspective on the key innovations that led to the development of some 27 licensed vaccines over the past two centuries and recent advances that promise to transform vaccines in the future. Technological revolutions such as reverse vaccinology, synthetic biology, and structure-based design transformed decades of vaccine failures into successful vaccines against meningococcus B and respiratory syncytial virus (RSV). Likewise, the speed and flexibility of mRNA vaccines profoundly altered vaccine development, and the advancement of novel adjuvants promises to revolutionize our ability to tune immunity. Here, we highlight exciting new advances in the field of systems immunology that are transforming our mechanistic understanding of the human immune response to vaccines and how to predict and manipulate them. Additionally, we discuss major immunological challenges such as learning how to stimulate durable protective immune response in humans.