HCV CHIM Community Advisory Committee

Seven members attended the videoconference meeting. In alphabetical order: Julia Bacon, Matt Bonn, Jake Eberts, Carrielynn Lund, Carolina Reid, Thomas Smiley, and Jennifer van Gennip. Dr. Jordan Feld, the study’s principal investigator, and Jenna Bavota, of the study team, attended to present updates; Prof. Karen Campbell also joined as a non-voting guest.

Study update

Dr. Jordan Feld presented an update on the study’s progress, largely for members’ situational awareness.

• The protocol remains under review by Health Canada. Dr. Feld characterized the regulator’s questions as appropriately careful and diligent.
• The team is preparing to collect plasma from a donor to serve as the inoculum, under good manufacturing practice (GMP) standards, through a partner organization. A feasibility “dress rehearsal” was carried out using an ineligible donor; it went well and surfaced a few minor issues that have since been addressed.
• An eligible and willing donor has been identified. Collection is targeted for roughly mid-July, after which the virus will be characterized (full sequencing, resistance testing, and sterility and biobanking checks).
• The donor will be treated and cured before their plasma is used; the cure will be confirmed three months after the eight-week treatment course. If characterization raises no concerns, the team hopes to receive Health Canada’s permission to proceed with the first infections in 2026.

Members raised several questions:

• Carrielynn Lund asked whether the donor would also be offered treatment. Dr. Feld confirmed that both donors and recipients will be treated, and that the donor’s plasma will not be used until their cure is confirmed.
•  Matt Bonn asked about the donor’s demographics and how they likely contracted hepatitis C. Dr. Feld said the donor is a healthy male in his late twenties, originally from India, with a genotype 1a infection — one of the two priority genotypes (alongside genotype 3) — likely acquired through medical exposure, and with no hepatitis B exposure (which would have been disqualifying).
• Jake Eberts asked how difficult it will be to find donors for the remaining genotypes. Dr. Feld said it is harder than initially expected because of the donor eligibility criteria (including that the first donor must be male, free of certain co-infections and cirrhosis, and without injection drug use in the past five years), but he expects suitable donors can be found with colleagues’ help. New infections in Toronto now split roughly evenly between genotypes 1 and 3.
• Jennifer van Gennip asked about the decision to have the donor wait until July for treatment. Dr. Feld explained that the ethics board asked the donor be treated within 12 weeks of consent, that this donor has no liver fibrosis (so a short delay carries minimal risk), and that he made clear to the donor they could begin treatment immediately if they preferred.

Vaccine candidate selection rubrics

Dr. Feld described the framework being developed to decide which vaccine candidates to test in the model, and why. Because there are likely only a limited number of CHIM attempts that can be run before confidence in the model could erode, candidates must be chosen to maximize the likelihood of success rather than by availability or by who is ready first.

• A workshop held in Toronto in February convened experts in three working groups: B-cell immunology, T-cell immunology, and practical (non-immunological) considerations such as the number of doses, the vaccine platform and its cost, and the route of administration. The practical-considerations group included people with lived experience and two CATIE members; the two immunology groups were limited to subject-matter experts.
• Each group drafted a rubric with minimum thresholds a candidate must meet and ranking criteria for comparing candidates that clear them. The developer of the HPV vaccine presented lessons from that vaccine’s development.
• The rubrics are near-final. Next steps are to circulate them more widely for feedback, finalize and publish them, and then convene a small independent panel (about five experts with no ties to any candidate) to apply them and decide the order in which candidates are tested.

Discussion:

• Carolina Reid asked whether the rubrics might prove too strict — whether no candidate would qualify — while noting that screening out weak candidates could itself be a useful outcome. Dr. Feld said the minimum thresholds were relatively modest, out of humility about what the field does not yet know (the correlates of protection are not established), but that a candidate unable to meet these criteria should not be tested, even if that means delay.
• Julia Bacon asked roughly how many candidates exist. Dr. Feld estimated six or seven groups worldwide (three in Europe, three in North America, one in Australia) with candidates showing good results in cells and animal models; each must first clear a Phase I trial. One Phase I study is underway, and the others likely have a path to Phase I within two to three years, suggesting a working lineup of three or four.
• Carrielynn Lund voiced strong support for the cautious, transparent approach, drawing on her experience with Indigenous communities during COVID and the real dangers of misinformation and mistrust. She emphasized building trust step by step, beginning at the testing stage. Dr. Feld agreed and noted the team hopes to hold further community-engagement events and will seek the board’s guidance on them.
• Thomas Smiley said the framework makes sense but raised a concern about the ranking stage: once several candidates pass the minimum threshold, how is the order decided without splitting hairs, and what prevents external or financial pressure to favor a particular candidate? Dr. Feld agreed the rubrics are not precise enough to simply score and rank, which is why an independent panel — rather than any single decision-maker, himself included — would weigh the data against the rubrics and reach a collective ranking. He noted he has already felt pressure from vaccine groups, which has reinforced his view that an arm’s-length, transparent process is needed.
• Carrielynn Lund suggested adding ethical oversight, at arm’s length, over how the team selects the panel and sets the criteria. Dr. Feld welcomed the suggestion and noted the panel’s membership is not finalized and may change as potential conflicts of interest evolve.

Dr. Feld invited written or verbal feedback on the rubrics, particularly the practical-considerations rubric, and said members are welcome to share them with knowledgeable colleagues, as they are not confidential.

Study logos

Jenna Bavota walked members through proposed logo options and two open questions: whether to use “hepatitis C” or “HepC,” and whether to use “CHIM” / “controlled human infection model” or “challenge.” The color scheme was chosen to match the UHN palette. Generally, the preference was spelling out “controlled human infection model” rather than relying on the “CHIM” acronym or the word “challenge”.

Jenna Bavota said she would circulate a poll afterwards for members to vote on their preferred logos.