The world’s first COVID-19 human challenge trial using the D614G strain of SARS-CoV-2 is underway in the United Kingdom. The Wellcome Trust is funding challenge stock preparation of the Beta variant (B.1.351) for a follow-up human challenge trial, and researchers at Imperial College London are considering conducting that trial. However, little has been written thus far about the ethical justifiability of human challenge trials with SARS-CoV-2 variants of concern. While vaccine resistance as such does not increase risks for volunteers in (...) COVID-19 challenge trials, we explore two specific characteristics of some variants that may initially be thought to make such trials unethical and conclude that SARS-CoV-2 variant challenge trials can remain ethical. (shrink)

TB human challenge studies could accelerate TB vaccine development by reducing uncertainty in early-stage vaccine testing, selecting promising vaccine candidates for large-scale field trials, and identifying an immune correlate of protection. However, ethical concerns regarding the exposure of trial participants and bystanders to significant risk have been a limiting factor for TB human challenge models. We analyze the expected social value and risks of different types of TB human challenge models, and conclude that given the massive public health burden of (...) TB, challenge models with even scant probabilities of expediting TB vaccine authorization have enormous expected humanitarian value, saving between 33,000 and 1,375,000 lives over the next ten years. We argue that attenuated M.tb challenge trials can be conducted ethically, and discuss the benefits and drawbacks of conducting virulent M.tb challenge trials. (shrink)

Ongoing and anticipated COVID-19 human challenge studies in the UK may advance our understanding of COVID-19 and facilitate the licensure of safe, effective, and easily deployable next-generation COVID-19 vaccines and boosters. We argue that international volunteer recruitment for COVID-19 human challenge trials can help promote diversity in these trials and ensure a sufficient number of eligible volunteers, both of which will increase the benefits of challenge research. We explore the ethical ramifications of dealing with unfair background conditions of global vaccine (...) injustice to expand medical research, and conclude that international recruitment for COVID-19 human challenge trials can be conducted ethically provided that several robust protections are in place for volunteers. (shrink)