Although human challenge studies (HCSs) have been widely employed in vaccine development for malaria, dengue, typhoid and cholera, the role of this research design in COVID-19 remains controversial. While the potential social value of HCSs in the context of a pandemic is clear, bioethicists are divided on the ethics, given that effective treatment for COVID-19 has eluded us to date. While compelling ethics arguments have been offered on both sides of the debate, scientific and regulatory complexities may not have been fully appreciated. Furthermore, accelerated development of efficacious vaccine candidates in traditional clinical trials has diluted some of the arguments in favour of HCSs. In low- and middle-income country settings, including South Africa, the need for robust patient care conditions for the conduct of HCSs, coupled with considerations such as perceptions of risk, consent processes, remuneration, vaccine hesitancy, fear of exploitation and access to vaccines, makes HCSs challenging to justify
