Hepatitis C kills hundreds of thousands of people worldwide each year; in Canada it results in more lost years of life than any other infectious disease. There is an effective treatment, but it is unavailable to many due to high cost and other access obstacles. And there’s no vaccine. Canada has the researchers, the policy framework and the capacity to help change that.
Last January, a drug called MAVIRET received Health Canada’s priority review approval. The drug, already used for treating chronic hepatitis C, can now be prescribed during the acute stage. This means that patients can be treated in the first six months after infection, before the virus has had time to permanently damage the liver. MAVIRET is the first direct-acting antiviral (DAA) approved in Canada that treats hepatitis C before it becomes chronic. We should feel optimistic about its potential. However, we also should bear in mind that its arrival, nearly four decades after the hepatitis C virus (HCV) was first identified, is still insufficient for addressing the disease burden of HCV in Canada
In 2018, a group of leading Canadian researchers called for an action plan to eliminate hepatitis C by 2030, a move that would bring Canada in line with the World Health Organization’s (WHO) goal of reducing global HCV infections by 80 per cent. Treatment has an important role to play in achieving this goal, but it remains costly and difficult to access globally and those who contract HCV can unintentionally infect others before their symptoms manifest. An estimated 8,200 Canadians were newly infected in 2021. And DAA does not prevent the reinfection of those who have previously contracted HCV. In fact, studies show that reinfection is common. For these reasons and others, leading researchers agree that Canada is unlikely to meet the WHO’s target, even with DAA.
Making treatment more affordable and accessible is a goal worth pursuing, but it does not eliminate the need for vaccine research. Fortunately, improving treatment access and supporting vaccine development are not competing priorities. They are two parts of a broader commitment that Canada has thus far only partially kept.
The Canadian Network on Hepatitis C (CanHepC), founded in 2015, has brought together more than 100 investigators, trainees and advocates nationwide to advance research on HCV prevention, treatment and outcomes. Its most recent meeting, last February in Toronto, included a workshop aimed at identifying the most promising vaccine candidates for clinical trials. The need is clear and the funding and institutional support are there.
So, what’s holding the research back?
Part of the answer is that a HCV vaccine is genuinely hard to develop. The virus mutates rapidly, exists in several genetically distinct forms and has evolved sophisticated defenses against the human immune system. Compounding this, the only animal that naturally contracts hepatitis C is the chimpanzee, a species that is banned for use in research in most countries. Without a reliable animal model, researchers have had to rely on trials in human populations, which are slower and more expensive.
The most recent such trial, which ran from 2012 to 2018, enrolled 548 people who injected drugs and found the vaccine candidate ineffective. Right now, there is no new vaccine efficacy trial underway. This is not because there are no promising candidates, but rather because the cost and complexity of field trials are so high that no one is willing to start one.
The economics compound the problem. Hepatitis C disproportionately affects poor and marginalized populations worldwide, weakening the commercial case for vaccine development. In Canada, for instance, HCV infection occurs disproportionately among Indigenous people, incarcerated people, men who have sex with men and people who use injection drugs. Structural barriers prevent treatment from reaching our society’s most vulnerable. But that is exactly why public funding and public leadership matter. And it is why Canada, a country with strong public health institutions, a commitment to health equity and world-class hepatitis C researchers, can act.
The key to moving HCV vaccine research forward in Canada may well exist in a controlled human infection model (CHIM), sometimes called a human challenge study. In these clinical trials, healthy adult volunteers are deliberately infected with a disease to test a vaccine. It is a model that has been applied to diseases including malaria, dysentery and COVID-19. And it is endorsed by leading universities in Canada and around the world. A hepatitis C challenge study could generate preliminary evidence demonstrating whether a vaccine works. It would require fewer participants and be held in a fraction of the time at a much lower cost than traditional field trials.
Hepatitis C is an unusually good candidate for human challenge studies. Acute infection is usually asymptomatic, so participants are unlikely to feel seriously unwell during the study period and will be treated before they are at risk of long-term effects. And participants can be administered DAA that can cure more than 95 per cent of cases without risk of long-term effects. The broadest evidence base comes from challenge studies for other diseases. A 2023 systematic review of more than 15,000 participants across more than 25 pathogens reported zero deaths and zero cases of permanent harm. That is an impressive safety record.
We also have a strong understanding of the longer-term risks associated with HCV infection. Liver damage takes years, typically decades, to develop. Two studies following people who were accidentally infected through contaminated blood products in Germany and Ireland found no elevated risk of liver cancer or cirrhosis among those who cleared the virus within months (which would be the case with challenge study participants).
This does not mean that participants would not incur risks, but rather that these risks would be minimized as much as possible through careful study design. Canadian researchers have insisted that participants in a challenge study would be monitored closely; strict eligibility criteria would screen out anyone of risk of complications; and the viral sample used to infect participants would come from a donor who has already been successfully cured with the same drugs that would be used to treat participants.
Test subjects would be healthy adult volunteers, screened for low complication risk, taking on a modest and temporary burden in place of those who cannot do so safely. Many are waiting for the chance to enroll in hepatitis C challenge trials, and Canadians have shown they are willing to take on the calculated risk that comes with challenge trial participation.
The expert consensus behind this approach is robust. A 2023 joint statement in support of hepatitis C challenge trials was signed by 121 researchers, ethicists and public health advocates, a group that included two of the three scientists who received the 2020 Nobel Prize for co-discovering hepatitis C. A 2026 article in Nature Reviews Immunology also describes controlled human infection models as offering a unique, if ethically complex, opportunity to accelerate HCV vaccine development.
Canada already has much of what is needed to act on these recommendations. Researchers at the University Health Network in Toronto have been taking steps to prepare for such trials should they be approved by Health Canada. What is needed now is a clear regulatory pathway. A guidance document, or even a pre-submission engagement process, would remove the largest single institutional barrier to launching challenge trials.
Every year without a hepatitis C vaccine is another year those communities carry a preventable burden.
Conflicts of interest:1Day Sooner is a non-profit that has promoted hepatitis C challenge trials in Canada for several years. The organization does not stand to materially gain from any clinical trials that should take place.
