HIASA Yoichi, MD, PhD | Ehime University Graduate School of Medicine; KOHARA Michinori, PhD; KOHARA Kyoko, PhD; ODA Yasunori, PhD; Yoshida Osamu, MD, PhD; NAGAI Masahiro, MD, PhD
Competition Sponsor: Japan Agency for Medical Research and Development
Awardee Year: 2025
Approximately 250 million people worldwide are infected with HBV, and high cancer rates pose significant threats to healthy longevity. For the treatment of hepatitis B, achieving “functional cure,” defined as the absence of HBs antigen and undetectable HBV-DNA, is a critical goal. However, this is challenging with standard nucleoside analog therapy.
We have developed a therapeutic vaccine capable of achieving functional cure. Using a nasal administrative vaccine formulation that contains HBs antigen, HBc antigen, and a viscosity-increasing, carboxyl vinyl polymer (CVP), we conducted Phase IIa clinical trial for patients with hepatitis B. The results confirmed safety and demonstrated to achieve functional cure in 13.8% of cases.
As a next idea, instead of using the “HBs-S antigen”, we considered using the “HBs-L antigen”. The HBs-L antigen induces antibodies against the pre-S1 region and has higher antiviral efficacy than the HBs-S antigen. However, the HBs-L antigen has genotype-specific amino acid sequences, making it difficult to achieve pan-genotype efficacy. Therefore, we designed a hybrid antigen (HBs-Lh antigen) in which the HBs-L antigens of genotypes C and D are expressed in the same membrane. When the HBs-Lh antigen was administered to mice, it neutralizes HBV infection in all genotypes A, B, C, and D. Additionally, it strongly induced HBV-specific cytotoxic T cells (CTLs) compared to HBs-S antigen.
We have developed an innovative intranasal therapeutic vaccine formulation, HBNET-369, which contains HBs-Lh antigen, HBc antigen, and CVP. HBNET-369 is expected to lead to functional cure, and contribute to extending global healthy life expectancy.