Hepatitis E vaccine landscape update 2025.

Introduction: Hepatitis E virus (HEV) is a significant public health concern, particularly in resource-limited and conflict-affected settings. While often self-limiting, HEV infection poses severe risks for pregnant women contracted with genotype 1 or 2, leading to high maternal mortality, and can cause chronic infection in immunocompromised individuals.

Areas covered: This review examines the epidemiology, clinical manifestations, and vaccine landscape of HEV, highlighting licensed and investigational candidates. We discuss HEV 239 vaccine the only licensed HEV vaccine which has shown high efficacy and cross-genotype protection, leading to approval in China and Pakistan. However, data gaps remain regarding its safety in pregnant women, children, and immunocompromised populations. WHO prequalification is needed for broader global access. We also review the current status of HEV vaccine development, and explore challenges, opportunities, and global policies, including efforts to improve outbreak response in high-risk settings.

Expert opinion: HEV vaccines are essential for disease control, but unresolved issues limit broader use. Conflicting data on miscarriage risk require further investigation. Ongoing trials in Pakistan and South Africa will offer key data on safety in pregnancy, immunogenicity in children, and use in people with HIV. WHO prequalification of HEV 239 vaccine is critical to expand access globally.