Viral hepatitis constitutes a substantial global public health challenge. The etiological agents, referred to as hepatitis viruses, are primarily categorized into five types: hepatitis A virus (HAV), hepatitis B virus (HBV), hepatitis C virus (HCV), hepatitis D virus (HDV), and hepatitis E virus (HEV). Among the various preventive strategies, vaccination is widely acknowledged as the most cost-effective and efficient method for controlling viral hepatitis and its related hepatic complications. To date, numerous countries have initiated extensive vaccination programs targeting hepatitis A and hepatitis B. Advances in biotechnology have facilitated substantial progress in vaccine formulation design, the development of innovative adjuvants, and the utilization of novel vectors. However, significant challenges persist, including inadequate vaccination coverage, inconsistent immune responses among vulnerable populations, and concerns regarding vaccine safety. This article presents a systematic review of recent advancements, the current status of vaccination efforts, and ongoing challenges associated with hepatitis vaccines, with the objective of providing critical insights to support the World Health Organization’s goal of eliminating viral hepatitis as a public health threat by 2030.

As a next-generation vaccine technology, mRNA vaccines mark a transformative advancement in vaccinology research. Their key strengths lie in rapid development cycles, high-efficiency manufacturing processes, robust immunogenic properties, and adaptable design frameworks. For infectious disease prevention, mRNA-based immunizations targeting SARS-CoV-2, such as the mRNA-1273 vaccine, have shown promising results in clinical evaluations. Validated efficacy metrics and safety profiles have supported their regulatory approval for public use. Additionally, mRNA platforms have shown substantial therapeutic potential against respiratory syncytial virus. However, this technology still faces multiple challenges, including poor stability, limited delivery efficiency, high production costs, unclear mechanisms of adverse reactions. Distinct from existing literature that primarily focuses on COVID-19 or specific delivery technologies, this review provides a comprehensive, integrated framework covering molecular design, delivery systems, and clinical translation across multiple viral pathogens, while also critically analyzing current controversies and future directions. This review aims to provide a comprehensive reference for researchers and clinicians in related fields.