Strategic and scientific contributions of human challenge trials for vaccine development: facts versus fantasy.
Yara-Natalie Abo, Euzebiusz Jamrozik, James S McCarthy, Meta Roestenberg, Andrew C Steer, Joshua Osowicki
Author Information
Yara-Natalie Abo: Tropical Diseases Research Group, Murdoch Children's Research Institute, Melbourne, VIC, Australia; Department of Paediatrics, The University of Melbourne, Parkville, VIC, Australia; Infectious Diseases Unit, Department of General Medicine, Royal Children's Hospital Melbourne, Parkville, VIC, Australia. Electronic address: yara-natalie.abo@rch.org.au.
Euzebiusz Jamrozik: Ethox and Pandemic Sciences Institute, Nuffield Department of Population Health, University of Oxford, Oxford, UK; Monash-WHO Collaborating Centre for Bioethics, Monash University, Melbourne, VIC, Australia.
James S McCarthy: Department of Infectious Diseases, The University of Melbourne, Parkville, VIC, Australia; Victorian Infectious Diseases Services, Royal Melbourne Hospital, Parkville, VIC, Australia.
Meta Roestenberg: Controlled Human Infections Center, Leiden University Medical Center, Leiden, Netherlands.
Andrew C Steer: Tropical Diseases Research Group, Murdoch Children's Research Institute, Melbourne, VIC, Australia; Department of Paediatrics, The University of Melbourne, Parkville, VIC, Australia; Infectious Diseases Unit, Department of General Medicine, Royal Children's Hospital Melbourne, Parkville, VIC, Australia.
Joshua Osowicki: Tropical Diseases Research Group, Murdoch Children's Research Institute, Melbourne, VIC, Australia; Department of Paediatrics, The University of Melbourne, Parkville, VIC, Australia; Infectious Diseases Unit, Department of General Medicine, Royal Children's Hospital Melbourne, Parkville, VIC, Australia.
The unprecedented speed of delivery of SARS-CoV-2 pandemic vaccines has redefined the limits for all vaccine development. Beyond the aspirational 100-day timeline for tomorrow's hypothetical pandemic vaccines, there is a sense of optimism that development of other high priority vaccines can be accelerated. Early in the COVID-19 pandemic, an intense and polarised academic and public discourse arose concerning the role of human challenge trials for vaccine development. A case was made for human challenge trials as a powerful tool to establish early proof-of-concept of vaccine efficacy in humans, inform vaccine down selection, and address crucial knowledge gaps regarding transmission, pathogenesis, and immune protection. We review the track record of human challenge trials contributing to the development of vaccines for 19 different pathogens and discuss relevant limitations, barriers, and pitfalls. This Review also highlights opportunities for efforts to broaden the scope and boost the effects of human challenge trials, to accelerate all vaccine development.
