Research progress on hepatitis A vaccine

<sec><p indent="0mm">Infection by the hepatitis A virus (HAV), which causes acute viral hepatitis A, continues to be a major cause of acute liver inflammation and jaundice worldwide. Although the broad deployment of inactivated and live-attenuated vaccines has substantially lowered the disease burden in many parts of the globe, HAV remains a persistent public health issue. In regions with limited sanitation infrastructure and developing countries, the virus is still highly endemic, frequently infecting young children. By contrast, in industrialized nations with improved hygiene and routine childhood immunization, incidence rates are generally low. This has, however, led to an accumulation of susceptible adults-a shift in epidemiology that paradoxically raises the risk of severe outbreaks through imported cases or local contamination of food and water. Thus, even in well-resourced settings, this enterically transmitted pathogen continues to present a tangible threat. </sec><sec> Advances in vaccine technology are now accelerating the development of second-generation HAV vaccines. Promising candidates, such as recombinant subunit vaccines and virus-like particle (VLP)-based formulations, offer potential solutions to certain constraints of current options. These include the cold-chain dependency of some live-attenuated vaccines and the multi-dose schedules required for durable immunity with inactivated vaccines. By building on progress in structural virology and immunology, these next-generation approaches aim to produce vaccines that are more stable, cost-effective, and potentially more immunogenic. </sec><sec> This review systematically examines the virological foundations of HAV relevant to vaccine design. We first outline the distinctive genomic organization of HAV, a positive-sense, single-stranded RNA virus belonging to the <italic>Picornaviridae</italic> family, and describe its capsid architecture. Special emphasis is placed on mapping its key antigenic epitopes, particularly those on the structural proteins VP1 and VP3 that are responsible for inducing neutralizing antibodies. A precise understanding of these epitopes is crucial for informed, rational vaccine development. </sec><sec> We then provide a detailed appraisal of currently licensed vaccines, covering their mechanisms of action, clinical efficacy, safety records, global deployment strategies, and recognized limitations, such as the potential waning of immunity in some groups or the uncertain need for booster doses over the very long term. </sec><sec> Finally, the article synthesizes recent advances in novel vaccine development. Beyond VLPs and recombinant proteins, we survey other innovative platforms, including DNA vaccines, viral-vectored constructs, and the emerging potential of mRNA technology against HAV. These candidates are evaluated in light of available preclinical and clinical data, with discussion of their relative strengths in safety, immunogenicity, manufacturing scalability, and thermal stability. </sec><sec> By integrating perspectives from fundamental virology, current clinical practice, and frontier biotechnologies, this review seeks to establish a coherent scientific foundation and conceptual framework to guide the design and development of next-generation hepatitis A vaccines, ultimately supporting progress toward global control and elimination of the disease. </sec>