Therapeutic Vaccines and the Global Divide in E-Antigen Disease

In "Therapeutic Vaccines and the Global Divide in E-Antigen Disease," our experts examine how geography shapes e-antigen disease and who these vaccine candidates could help most.

Dr. Chung turns to therapeutic vaccines designed to engage T-cell responses central to controlling and clearing chronic viral infections, asking Dr. Gish how candidates like GS-2829 and GS-6779 conceptually differ from other strategies, and how to interpret one study's 45% e-antigen loss rate by day 85 given the small size of these studies.

Dr. Gish reframes the discussion around e-antigen itself, drawing on his experience working on hepatitis B across nearly every continent. He notes that e-antigen-positive patients represent a distinct minority in most of the western world, while in places like Vietnam and parts of Africa, 50% to 60% of patients may be e-antigen positive, reflecting younger populations infected before the virus shifts through core and pre-core mutations that reduce e-antigen production below detectable levels. This makes it a moderate-sized market concentrated in developing and lower- and middle-income countries, though a valuable proving ground for new therapies.

Turning to GS-2829 and GS-6779, vector-based therapeutic vaccines developed through a Gilead and Hookipa Pharma collaboration, he explains that one uses a Pichinde virus vector and the other a replication-incompetent lymphocytic choriomeningitis virus vector, both designed to induce a polyfunctional CD8 T-cell response and high levels of neutralizing antibodies. He says he has historically been skeptical of neutralizing antibodies but now sees them evolving into immune-modulating antibodies, particularly relevant to hepatitis Delta, that create an immune stimulation background. While the e-antigen signal is exciting for the minority of patients who could benefit, he flags patient concerns about receiving viral vectors as a barrier requiring strong safety and efficacy data, adding that immune modulation, including a renewed role for newer interferon formulations, remains key to this approach.

The next episode in this series, "Preparing Practices for the Next Era of Hepatitis B Care," looks at what practices need to do to get ready for this expanding landscape.