Novel Hepatitis B Vaccines Show Promise in Phase 1a Study: Safety and Immunogenicity Results for GS-2829 and GS-6779
Therapeutic vaccines GS-2829 and GS-6779 demonstrate immune responses and strong safety profile, showing potential to contribute to global hepatitis B elimination efforts.
A Phase 1a study in New Zealand evaluated the safety, tolerability, and immunogenicity of two novel arenaviral vectored vaccines, GS-2829 and GS-6779, for hepatitis B virus (HBV) infection. The study enrolled 51 healthy participants, aged 33 on average, who received varying doses of the vaccines via intramuscular administration to assess safety and immune response. The results were presented at the 2025 International Liver Congress (EASL).
Safety results from the study showed that treatment-emergent adverse events (TEAEs) occurred in 98% of participants. Most of the adverse events were mild to moderate (Grade 1 or 2) and transient, including injection site reactions (55%), as well as flu-like symptoms such as headache (43%), fatigue (41%), and malaise (25%). Only one serious adverse event (SAE), a Lisfranc fracture caused by a road collision, was reported and was unrelated to the vaccine. Notably, no participants had to discontinue the vaccine, and there were no deaths, indicating that the vaccines were well tolerated by the participants.
The study also evaluated the immunogenicity of the vaccines. The results revealed that both GS-2829 and GS-6779 elicited dose-dependent immune responses. Participants demonstrated robust HBV-specific T cell responses to all encoded HBV antigens and produced high levels of anti-HBsAg antibodies that were durable over time. In cohort C8, where participants received additional doses (5 and 6), the magnitude of T cell responses was significantly enhanced, suggesting that repeated dosing could further improve immune responses. These findings indicate that both vaccines have the potential to generate strong and sustained immunity against HBV.
“We knew we had to induce robust T cell responses in addition to B cell responses,” said Anu Oshinusi, MD, MPH, vice president of clinical research at Gilead Sciences. “This is different from your typical prophylactic vaccines. By including multiple well-conserved hepatitis B antigens and allowing for repeated dosing, we’ve been able to maximize the immune response.” Oshinusi further emphasized that the design of the vaccines prevents the development of anti-vector neutralizing antibodies, ensuring that subsequent doses remain effective.
The encouraging safety and immunogenicity data presented in this Phase 1a study lay the groundwork for further investigation of GS-2829 and GS-6779 in individuals with chronic hepatitis B. As Oshinusi explained, “We are hoping to show data in patients with virally suppressed chronic hepatitis B in the near future, as part of the Phase 1b portion of this study.” The ultimate goal is to develop a vaccine that, in combination with other agents, could help achieve a functional cure for HBV. A functional cure would mean that after completing therapy, patients could control their chronic HBV infection without the need for ongoing treatment.
From a public health perspective, a successful therapeutic HBV vaccine could be transformative, especially in high-burden, resource-limited settings. “This vaccine could eliminate the need for lifelong antiviral therapy, reduce stigma, and alleviate concerns about transmission,” said Oshinusi. The WHO has set a target to eliminate viral hepatitis as a public health threat by 2030, and Oshinusi sees a therapeutic HBV vaccine as a key component in achieving that goal.
“We’ve made great strides in managing hepatitis C and turning hepatitis B into a manageable condition,” she added. “A therapeutic hepatitis B vaccine, combined with other agents, could significantly reduce the burden of liver disease, particularly in areas where lifelong antiviral therapy isn’t always accessible.” The findings from this study suggest that GS-2829 and GS-6779 could be an important part of global efforts to eliminate hepatitis B.
