The Precision Vaccines Program (PVP) is an academic research program that applies precision medicine principles to vaccinology to discover and develop next generation vaccines tailored to vulnerable populations. It conducts basic and translational research to develop novel vaccines and therapeutics for diseases that affect vulnerable populations such as infants, older adults, those with chronic disease and those who are immunocompromised. The PVP employs approaches such as modeling vaccine-induced human immune responses in vitro using a variety of platforms, adjuvant screening/discovery, systems biology, animal studies, and clinical trials to accelerate and de-risk development of vaccines optimized for populations with distinct immune responses, including those at the extremes of age who suffer the most infections. PVP faculty lead several NIH/NIAID-supported studies, including: (a) Adjuvant Discovery and Development Program contracts, leveraging robotic and immunologic approaches to discover, characterize, and formulate novel small molecule adjuvants that may enhance vaccine responses of the young and the elderly; (b) an international Human Immunology Project Consortium effort employing systems biology to define biomarkers of neonatal vaccine immunogenicity; (c) coronavirus/COVID-related studies including a national effort to discover biomarkers of COVID disease severity and a project to discover and develop novel coronavirus vaccines; (d) development of adjuvanted vaccines to prevent pertussis (whooping cough), respiratory syncytial virus, and HIV as well as overdose in opioid users; and (e) an Immune Development in Early Life (IDEAL) study that aims to increase infant vaccine responsiveness and decrease childhood respiratory disease.