Myron M. LevineSalim AbdullahYaseen M. ArabiDelese Mimi DarkoAnna P. DurbinVicente EstradaEuzebiusz JamrozikPeter G. KremsnerRosanna LagosPunnee PitisuttithumStanley A. PlotkinRobert SauerweinSheng Li ShiHalvor SommerfeltKanta SubbaraoJohn J. TreanorSudhanshu VratiDeborah KingShobana BalasingamCharlie WellerAnastazia Older AguilarM. Cristina CassettiPhilip R. KrauseAna Maria Henao RestrepoFaculty of Tropical Medicine, Mahidol UniversityRegional Centre for BiotechnologyCentro para Vacunas en Desarrollo ChileKing Saud bin Abdulaziz University for Health SciencesIfakara Health InstituteUniversitetet i BergenWuhan Institute of Virology Chinese Academy of SciencesUniversidad Complutense de MadridOrganisation Mondiale de la SantéUniversity of MelbourneUniversity of Rochester Medical CenterUniversitätsklinikum und Medizinische Fakultät TübingenBill and Melinda Gates FoundationWellcome TrustMonash UniversityNational Institute of Allergy and Infectious Diseases (NIAID)Radboud UniversiteitUniversity of Maryland School of MedicineFood and Drug AdministrationUniversity of PennsylvaniaJohns Hopkins Bloomberg School of Public HealthWHO RandD Blueprint COVID-19 Vaccines Working GroupCentre de Recherches Médicales de Lambaréné2022-08-042022-08-042021-06-01Clinical Infectious Diseases. Vol.72, No.11 (2021), 2035-204115376591105848382-s2.0-85094964919https://repository.li.mahidol.ac.th/handle/20.500.14594/78189WHO convened an Advisory Group (AG) to consider the feasibility, potential value, and limitations of establishing a closely-monitored challenge model of experimental severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and coronavirus disease 2019 (COVID-19) in healthy adult volunteers. The AG included experts in design, establishment, and performance of challenges. This report summarizes issues that render a COVID-19 model daunting to establish (the potential of SARS-CoV-2 to cause severe/fatal illness, its high transmissibility, and lack of a "rescue treatment"to prevent progression from mild/moderate to severe clinical illness) and it proffers prudent strategies for stepwise model development, challenge virus selection, guidelines for manufacturing challenge doses, and ways to contain SARS-CoV-2 and prevent transmission to household/community contacts. A COVID-19 model could demonstrate protection against virus shedding and/or illness induced by prior SARS-CoV-2 challenge or vaccination. A limitation of the model is that vaccine efficacy in experimentally challenged healthy young adults cannot per se be extrapolated to predict efficacy in elderly/high-risk adults.Mahidol UniversityMedicineReviewSCOPUS10.1093/cid/ciaa1290