121 Sign Letter for Hepatitis C Human Challenge Studies

20 years ago, it would have been a shocking idea — but thanks to advances in treatment and knowledge of the disease, increasing numbers of experts believe infecting volunteers with hepatitis C for limited periods of time (in a human challenge study) will be the key to developing a vaccine. That’s why 121 people — including five Nobel prize winners, dozens of physicians, scientists, ethicists, and other public health advocates signed 1Day Sooner’s open letter in support of developing hepatitis C human challenge studies (also called controlled human infection models, CHIM).

Below are excerpts from the open letter, published in The Lancet Gastroenterology & Hepatology in September 2023:

It is only because of the remarkably effective treatments that we can now consider human challenge studies for hepatitis C. … We are confident that in the era of DAAs [direct-acting antiviral treatments], human challenge studies can be done in accordance with the highest ethical and safety standards.

Human challenge studies for a hepatitis C vaccine could accelerate vaccine development dramatically. The effort to establish the model and test an initial vaccine candidate could take as little as 3 years. If that candidate fails, subsequent studies to test others could provide evidence of efficacy as quickly as 1 year.

The impact of a vaccine would be enormous: reducing transmission, preventing cirrhosis, and most importantly, markedly reducing the rate of liver cancer, the world’s second-most deadly cancer in terms of total fatalities. … With the prospect of such a significant advance, we have confidence that people will volunteer to participate in hepatitis C challenge studies.

For an academic examination of hepatitis C challenge studies and related scientific and ethical questions, see the dedicated August 2023 supplement in Clinical Infectious Diseases.

1Day Sooner, a nonprofit advocacy group for healthy medical volunteers, is working with researchers to realize proposed human challenge studies for hepatitis C in Canada, the United Kingdom, and the United States. In a human challenge study, adult volunteers are deliberately infected with a disease so that new vaccines and treatments can be tested.

Hepatitis C is a liver infection caused by the hepatitis C virus (HCV). Hepatitis C is a blood-borne virus, primarily transmitted through shared needles or other sharp instruments. It’s treatable, but there is no vaccine. Tens of millions of people around the world have hepatitis C, and most don’t know it — it causes damage to the liver slowly, usually over decades, but for most people there aren’t other noticeable symptoms. Over half a million people are killed each year by hepatitis C.

Even though treatment for hepatitis C is effective, in the last ten years, the number of total infections worldwide has barely budged — but with a vaccine and treatments, there’d be a way to one day wipe out hepatitis C for good.

Still, hepatitis C vaccines have not been a major priority in part because it is so difficult to test them. People who inject drugs (PWIDs) are the only population with sufficiently high transmission rates to enable early vaccine efficacy studies. These studies require major harm reduction interventions that protect the PWID participants, but also slow the pace by reducing natural hepatitis C infection rates needed to determine efficacy. The most recent hepatitis C vaccine study among PWIDs took six years to complete, ending in 2018 (Page et al., 2021). There hasn’t been another one started since then.

Challenge studies can provide quick results using a fraction of the volunteers in a fraction of the time. That is why numerous researchers — including signatories to 1Day Sooner’s open letter — believe challenge studies are the only realistic option to develop a hepatitis C vaccine, especially considering the lack of suitable animal models (Liang, Feld, Cox & Rice, 2021). Volunteers, likely up to one hundred for a trial of a single vaccine, would be infected for up to six months before the initiation of free treatment.

A very simplified diagram of how a vaccine efficacy CHIM (controlled human infection model) study, also known as a human challenge study, would work. DAA = direct-acting antiviral, a class of highly effective drugs used to treat hepatitis C.

Challenge studies could make hepatitis C vaccine development faster and more efficient in three ways:

  • by “down-selecting” early vaccines in development, ensuring that only the most promising candidates are allocated resources for larger, more expensive, and time-consuming studies
  • by providing specific, detailed information about infections and immune responses, challenge studies give unique insight into the body’s response to a disease, which allows scientists to quickly fine-tune further research and development of vaccines and drugs
  • in combination with later trials in higher-incidence groups, like people who inject drugs, human challenge studies could substantially shorten the pathway to regulatory approval and general vaccine deployment

What are others saying?

Carolina Reid

Carolina grew up knowing her father had hepatitis C. “I was raised to believe that this disease would one day take his life and knew it caused serious impact through infection throughout the rest of the world,” she told 1Day Sooner. Thankfully, he was eventually cured — but most of the tens of millions of people who have hepatitis C worldwide are not so fortunate to receive treatment.

As an adult, Carolina volunteered in a human challenge study for malaria, complete with infection through mosquito bites. She now is on an advisory board assisting researchers developing the hepatitis C challenge model — and would “absolutely” consider enrolling herself, too!

Dr. Harvey Alter

Dr. Alter was one of three scientists awarded the 2020 Nobel Prize in Physiology or Medicine for the discovery of the hepatitis C virus (HCV) in 1989, along with Charles Rice, another signatory to the open letter, and Michael Houghton.

Since that discovery, so much progress has been made in the fight against this disease, but a vaccine is still needed. “I believe a hepatitis C challenge model is our best shot at developing a vaccine in the near future,” says Dr. Alter. “Such a model is possible because current HCV treatments can cure virtually 100% of HCV-infected individuals.”

William Remak

Bill is the chairman of the California Hepatitis C Task Force and a former hepatitis C patient himself. He was hospitalized in 1966 for what was at the time an unknown viral hepatitis — the hepatitis C virus would remain undiscovered for over 30 years. Bill became a staunch advocate for hepatitis C patients, and was finally cured in 2016. His experience has convinced him of the need for a vaccine. Over the course of his lifetime, Bill says, “my own care has easily exceeded 5 million dollars,” a huge sum that vaccines could prevent befalling others.

Tyler Soga

Tyler witnesses the harm of hepatitis C on a regular basis. “As a nurse practitioner working with patient populations in correctional facilities and with substance use disorders, my patients frequently suffer from HCV,” he notes. Asked whether he’d consider volunteering himself, Tyler explains his enthusiasm: “I think the risks of intentionally being infected with HCV in the aims of creating a vaccine for HCV are wildly outweighed by the potential gains… [and] there’s something pretty damn cool about playing an important part in science and medicine.”

Julia Bacon

Julia, of Toronto, Canada, is studying to regain her nursing license, having relinquished it following her struggle with injection drug use. In the industrialized world, it’s mostly people who injected drugs who contract hepatitis C. Julia’s immune system cleared hepatitis C on its own after she was infected, but most are not so lucky. Because she has previously had hepatitis C, she is ineligible for any human challenge study, but she’s inspired by the “beacons of hope” who would eventually volunteer: “I admire the selflessness and courage it takes to be infected with this disease so that some day people (such as my fellow addicts still struggling) don’t have to suffer by contracting it.”