Long-Term Persistence of Anti-HAV Antibody Conferred by a Single Dose of Live-Attenuated Hepatitis A Vaccine: Results from 17-Year Follow-Up

Abstract

OBJECTIVES: With implementation of mass immunization and improvements in sanitation, China is moving rapidly from high to low endemicity of hepatitis A (HA). To prevent a resurgence after intense vaccination, a comprehensive and systematic assessment of long-term protection against HA conferred by vaccine was thus performed. METHODS: In 1996, 3,515 susceptible children aged one to 12 years were recruited in a randomized, open trial to assess the efficacy of a live-attenuated HA vaccine. During a 17-year follow-up period, children were tested for antibody persistence and long-term protection against both hepatitis A virus (HAV) disease and infection. Case finding was conducted using the China National Notifiable Infectious Disease Reporting System. Serum anti-HAV antibody levels were evaluated by the ELISA method to ascertain antibody persistence and protection against infection. RESULTS: During the 17-year follow-up, 2,132 (61%) children from the initial cohort were available for analysis. After calibrating the sensitivity of assay, excluding natural infection and vaccine booster, the sero-positive rate and the geometric mean concentrations declined from 94.9% and 131.3 mIU/mL (91.5-188.4mIU/mL) at the peak to 55.6% and 41.1 mIU/mL (95% CI: 27.8-61.0 mIU/mL) respectively, with a similar natural infection rate in both groups. CONCLUSIONS: This study demonstrates that long-term protection against hepatitis A persists at least for 17 years after administration of a single dose of a live-attenuated HA vaccine and suggests that a booster dose is currently not necessary. FUNDING STATEMENT: This work was supported by grants from National Natural Science Foundation (China) (81072346), National Science and Technology Project of Major Infectious Diseases (2008ZX10002-003, 2012ZX10002002004) DECLARATION OF INTERESTS: The authors declare that they have no competing interests. ETHICS APPROVAL STATEMENT: This study was reviewed and approved by the Institutional Review Board of the Institutes of Biomedical Sciences, Fudan University. Written inform consent was obtained from each participant.