Abstract
Clinical trials that use human challenge, also known as controlled human infection models (CHIMs), have rapidly advanced vaccine development for multiple pathogens, including at least 30 disease models to date. CHIM studies, championed by networks of researchers, regulators, ethicists, technical experts, and other stakeholders, limit exposure of individuals to an investigational product, de-risk product investments, identify correlates of protection, and, most importantly, provide a prompt readout of vaccine efficacy. While CHIM studies provide multiple advantages, important challenges exist, including strengthening the relevance and comparability of CHIM study results to efficacy trials in endemic areas, particularly in resource-limited settings.