The COVID-19 Human Challenge Programme, funded through the UK Government’s Vaccines Taskforce, is being run in partnership with Imperial College London, the Department for Business, Energy & Industrial Strategy (BEIS), hVIVO, a leading clinical company with expertise in viral human challenge models, and the Royal Free London NHS Foundation Trust.

The first phase of the trial, known as a virus characterisation study, will explore the feasibility of exposing healthy volunteers to the SARS-CoV-2 coronavirus. Initially, the main aim will be to discover the smallest amount of virus it takes to cause a person to develop asymptomatic or mild COVID-19.

The study will recruit healthy volunteers aged between 18 and 30 with no previous history of COVID-19, no underlying health conditions and no known adverse risk factors for COVID-19, such as heart disease, diabetes or obesity.

Once the initial phase is complete, clinical researchers will use this human challenge model to study how different vaccines work in the body to stop or prevent COVID-19 and test potential treatments.

Leading UCL clinical academics who work the Royal Free Hospital trial site, will be involved in the direct clinical care of participants, including Dr Sir Mike Jacobs (Division of Infection & Immunity).

In addition, scientists in the UCL Division of Infection & Immunity, in collaboration with teams at Imperial College London, will also carry out critical research using new cutting-edge approaches to assessing the human immune response.

This work, coordinated by Professor Emma Morris (Director, Division of Infection & Immunity) and Professor Robert Heyderman (Head, Research Department of Infection) will exploit world-leading research at UCL in understanding both innate and adaptive immune responses to infection.

Professor Morris said: “These studies are aimed at maximising our understanding of how the immune system reacts to the virus very early after infection, and whether variations in this response predict protection by vaccines. This will also allow us to understand more fully which treatments are likely to be the most effective.”

This research will be carried out in specialist laboratories across UCL including the new UCL Institute of Immunity & Transplantation in the recently opened Pears Building on the Royal Free Hospital site – a joint venture between UCL, the Royal Free Charity and the Royal Free London Hospitals NHS FT.

Manufacturing the virus

In readiness for the study, a team led by Professor Judith Breuer (UCL Pathogen Genomics Unit and UCL GOS Institute of Child Health) has been working with hVivo on the production of the SARS-CoV-2 virus strain that will be used in the planned trial.

Specifically, the UCL PGU has undertaken sequencing of the virus as part of the quality assurance required before the SARS-CoV-2 challenge can be undertaken.

Professor Breuer said: “We at the PGU are delighted to have been involved with hVivo in developing the virus that will be used for the vaccine challenge studies.

“It is critically important work to ensure we know exactly what the virus sequence is. We look forward to collaborating on future research in this important area”

The UCL PGU has been established for 10 years during which time it has pioneered pathogen sequencing with a particular focus on high fidelity methods that introduce minimal methodological artefact. The work with hVivo has been carried out at the Zayed Centre for Research into Rare Disease in Children, a partnership between Great Ormond Street Hospital, UCL and Great Ormond Street Hospital Children’s Charity. The Zayed Centre for Research is the largest single academic manufacturing unit for gene and cell therapies in the UK and one of the largest in the world.

What are human challenge studies?

Human challenge studies help clinical researchers establish which vaccines are most likely to succeed and have been used for example for the evaluation of influenza, pneumonia, malaria and typhoid vaccines. As the prevalence of COVID-19 rises and falls in populations, it can make it difficult for traditional vaccine trials to assess if vaccines work, because volunteers receiving the vaccine may not be naturally exposed to the virus. Because a human challenge study deliberately and safely infects the volunteers it should be possible for scientists to begin to establish efficacy very quickly, by testing if those who have had a vaccine are less likely to become infected with the virus.

Human challenge studies also make it possible for scientists to compare the efficacy of vaccine candidates by testing them side by side to establish which is more effective. At this early stage, no specific vaccine candidates for the human challenge trials have been confirmed.

First steps

Initially, researchers will assess what amount of virus is needed to safely cause infection and elicit an immune response by slowly increasing the viral dose to which small groups of volunteers are exposed. The proportion of participants becoming infected and the amount of virus that they subsequently shed will be tracked to better understand the course of infection.

As higher viral doses may be linked to more severe outcomes, the researchers are aiming to infect volunteers with the lowest possible dose to trigger viral replication but minimise symptoms. Before leaving the residential clinical facility, volunteers would be required to test negative for the presence of SARS-CoV-2 in two separate laboratory tests, highly sensitive to the presence of the virus.

The human challenge study will be reviewed by a specially convened ethics committee before any volunteers are enrolled and the Medicines and Healthcare products Regulatory Agency (MHRA), an exemplar globally of medicines and device regulation, will be asked to approve the study before it is conducted. The studies will be overseen by an independent safety committee of experts.

Dr Chris Chiu, from the Department of Infectious Disease at Imperial College London and lead researcher on the human challenge studies, said: “Human challenge studies can increase our understanding of COVID-19 in unique ways and accelerate the development of the many potential new COVID-19 treatments and vaccines.

“Our number one priority is the safety of the volunteers. My team has been safely running human challenge studies with other respiratory viruses for over 10 years. No study is completely risk-free, but the Human Challenge Programme partners will be working hard to ensure we make the risks as low as we possibly can.

“The UK’s experience and expertise in human challenge trials as well as in wider COVID-19 science will help us tackle the pandemic, benefiting people in the UK and worldwide."

Viral insights

Since the start of the global pandemic, doctors have learned a great deal about how the SARS-CoV-2 virus spreads and which groups may be at increased risk, as well as gaining clinical insights into treatments which can reduce the severity of disease and its complications.

However, despite these advances, there remain very few therapies for treating patients with COVID-19 and there is no effective vaccine available. Human challenge studies could be a crucial component of progressing research into treating and preventing the disease.

Professor Peter Openshaw, co-investigator on the study and Director of the MRC-funded Human Challenge Consortium (HIC-Vac) at Imperial College London said: “Deliberately infecting volunteers with a known human pathogen is never undertaken lightly. However, such studies are enormously informative about a disease, even one so well studied as COVID-19.

“It is really vital that we move as fast as possible towards getting effective vaccines and other treatments for COVID-19, and challenge studies have the potential to accelerate and de-risk the development of novel drugs and vaccines. These studies form a part of the global effort and play to a unique strength that we have at Imperial and in the UK”.

Trial participation

Subject to ethics approval, the first study would start in early 2021 and focus on identifying the lowest levels of the virus needed to infect healthy consenting adult volunteers.

Anyone interested in registering their interest in future COVID-19 human challenge study research should visit: ukcovidchallenge.com

Links

Image

Further information