Hepatitis B Vaccine: Time to Rethink Our Correlate of Protection

Abstract

Hepatitis B virus (HBV) remains a major global public health concern despite the transformative impact of widespread vaccination. Although the introduction of universal immunization programs has markedly reduced HBV prevalence, particularly in children, the persistence of infection in high-risk adult populations underscores the need for continued vigilance. This review synthesizes current data on the global and United States burden of hepatitis B, the natural immune responses to infection, and the mechanisms by which vaccine-induced protection is sustained. A central focus is the long-term durability of immune memory, even in the setting of declining or undetectable antibody to hepatitis B surface antigen levels. Drawing from epidemiologic cohorts and mechanistic studies, we highlight the role of T- and B-cell memory in conferring sustained protection and argue for a reevaluation of current revaccination strategies. The evidence reviewed challenges the clinical overreliance on static serologic thresholds and supports a model of pathogen-specific immunologic assessment, particularly for viruses with prolonged incubation periods such as HBV. These findings have direct implications for public health policy and underscore the need for nuanced, mechanistically grounded approaches to booster vaccination and immunity surveillance.