<h4>Introduction</h4>Preparation for a future pandemic or serious epidemic caused by a known or yet unknown pathogen (Disease X) is a global health priority. Controlled human infection studies (CHIS) are recognised as a valuable tool to accelerate development of vaccines and immunotherapeutics against pathogens with pandemic potential and may play a role in future pandemic settings. The acceptability of CHIS to potential participants in a pandemic setting has not been explored.<h4>Methods</h4>A mixed-methods study of adults screened to participate in a first-in-human SARS-CoV-2 vaccine trial, using online survey and interviews, was undertaken between September and October 2020 in Oxford, UK. This work assessed individuals' views, motivations and experiences of participating in a trial during a pandemic setting, including attitudes towards a hypothetical SARS-CoV-2 CHIS.<h4>Results</h4>349 of 770 (45%) invited individuals completed the survey, and 102 survey respondents (29%) participated in a structured interview. Participants were highly educated, research informed and predominantly of white ethnicity. Approximately a third of survey respondents agreed they would be willing to participate in a hypothetical SARS-CoV-2 CHIS. Individuals aged <35 years old, those without children and those who were single were more likely to agree to participate in a hypothetical SARS-CoV-2 CHIS. This decision was dependent on short-term and long-term complications of infection, availability of rescue therapy, likelihood of CHIS to accelerate vaccine development and urgency of the public health need. Motivations to participate in a SARS-CoV-2 CHIS included altruism and a preference to acquire infection of a circulating pandemic pathogen in a controlled setting. The views of family and friends were important in individuals' decision-making.<h4>Conclusions</h4>Vaccine trial participants are an informed and motivated public group who can provide situated public expertise for CHIS pandemic preparedness. Recruitment to CHIS in a pandemic may be more efficient if targeted to younger, single individuals without children. Media engagement and information specifically for potential CHIS participants' families is important to facilitate informed discussion.

In the pandemic context several specificities should be underlined for the case of vaccine trials, in addition to all ethical concerns raised for research related to pharmacological treatments which are also valid for vaccine research. Study population in vaccine trials is built up with healthy volunteers that should be carefully and fairly selected; as far as vaccine for emergency use are approved, the use of placebo in controlled studies raises ethical questions that should be discussed. Participants in vaccine trials should in any case be unduly influenced by any form of payment, and the gratuity of their act should be stressed in the communication and consent process. Moreover, in the context of experimentation with vaccines, sensitive ethical issues can arise also from the so-called "challenge studies", since they concern intentionally infecting healthy people to investigate diseases and their treatments (human challenge trials involve exposing healthy volunteers to a pathogen to learn more about the disease it causes and to test vaccines quickly). The contribution finally includes a specific list of aspects to be included in well-designed information and consent process for participants' in vaccine research in the Covid-19 pandemic.

SARS-CoV-2, the virus that causes COVID-19, was isolated in late 2019. Its genetic sequence was published on 11 January 2020, setting off an intense research SARS-CoV-2, the virus that causes COVID-19, was isolated in late 2019. Its genetic sequence was published on 11 January 2020, setting off an intense research effort to develop a COVID-19 vaccine. Vaccine development was expedited via unprecedented collaboration between academia, the pharmaceutical industry and governments. By June 2020, tens of billions of dollars were being invested to develop d After a coronavirus was isolated in December 2019, its genetic sequence was published on 11 January 2020, triggering an urgent international response to prepare for an outbreak and hasten development of a preventive vaccine. In February 2020, the WHO said it did not expect a vaccine against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative virus, to become available in less than 18 months. The rapidly growing infection rate of COVID‑19 worldwide during 2020 stimulated international alliances and government efforts to urgently organize resources to make multiple vaccines on shortened timelines, with four vaccine candidates entering human evaluation in March (see the table of clinical trials started in 2020, below). By April 2020, "almost 80 companies and institutes in 19 countries" were working on this virtual gold rush. Also in April, CEPI estimated that as many as six of the vaccine candidates against COVID‑19 should be chosen by… Although the… Challenge studies are a type of clinical trial involving the intentional exposure of the test subject to the condition tested, an approach that can significantly accelerate vaccine development. Human challenge studies may be ethically controversial because they involve exposing test subjects to dangers beyond those posed by potential side effects of the substance being tested. Challenge studies have been used for diseases less deadly than COVID‑19 infection, such as common influenza, typhoid fever, cholera, and malaria. The World Health Organization developed a guidance document with criteria for conducting COVID‑19 challenge studies in healthy people, including scientific and ethical evaluation, public consultation and coordination, selection and informed consent of the participants, and monitoring by independent experts. Beginning in January 2021, dozens of young adult volunteers will be deliberately infected with COVID‑19 in a challenge trial conducted in a London hospital under management by the British government COVID‑19 Vaccine Taskforce. Once an infection dose of COVID‑19 is identified, two or more of the candidate COVID‑19 vaccines will be tested for effectiveness in preventing infection.