Protective efficacy of GMAI-02, a cDNA-derived inactivated hepatitis A vaccine, against HM175/mp7 challenge in...

Hepatitis A virus (HAV) infection is preventable by vaccination, and all currently licensed HAV vaccines have been evaluated for their preclinical efficacy in nonhuman primates. However, interferon (IFN) receptor-knockout mice are susceptible to HAV infection. In this study, we developed GMAI-02, a cDNA-derived, inactivated, aluminum-adjuvanted HAV vaccine candidate, and evaluated its immunogenicity in Institute of Cancer Research (ICR) mice and its efficacy in AG129 mice lacking type I (IFN-α/β) and type II (IFN-γ) receptors. Based on dose-ranging studies in ICR mice, the adult dose of GMAI-02 was established as 30 IU/mL. AG129 mice were immunized twice with the hepatitis A vaccine, followed by challenge with the HM175/mp7 virus. Post-challenge, the serum alanine aminotransferase levels remained very low, fecal viral shedding was undetectable, hepatic viral replication was markedly reduced relative to positive controls (challenge without vaccination), and histopathological liver lesions were substantially attenuated. These data indicate that GMAI-02 elicits robust humoral responses and confers protection against HAV challenge in the AG129 model. Our findings support conducting nonclinical efficacy assessments of hepatitis A vaccines in accessible mouse models, thereby reducing the reliance on nonhuman primates.