Long-term anti-HBs antibody persistence following infant vaccination against hepatitis B and evaluation of anamnestic response

Abstract

Hepatitis B vaccine has been available worldwide since the mid-1980s. This vaccine was evaluated in a clinical trial in Thailand, conducted on subjects born to hepatitis B surface antigen positive and hepatitis B e-antigen positive mothers and vaccinated according to a 4-dose schedule at 0, 1, 2 and 12 mo of age and a single dose of hepatitis B immunoglobulin concomitantly at birth. All enrolled subjects seroconverted and were followed for 20 y to assess the persistence of antibody to the hepatitis B surface antigen (anti-HBs) (NCT00240539). At year 20, 64% of subjects had anti-HBs antibody concentrations ≥ 10 milli-international units per milli liter (mIU/ml) and 92% of subjects had detectable levels (≥ 3.3 mIU/ml) of anti-HBs antibodies. At year 20, subjects with anti-HBs antibody titer < 100 mIU/ml were offered an additional dose of hepatitis B virus (HBV) vaccine to assess immune memory (NCT00657657). Anamnestic response to the challenge dose was observed in 96.6% of subjects with an 82-fold (13.2 to 1082.4 mIU/ml) increase in anti-HBs antibody geometric mean concentrations. This study confirms the long-term immunogenicity of the 4-dose regimen of the HBV vaccine eliciting long-term persistence of antibodies and immune memory against hepatitis B for up to at least 20 y after vaccination.

Keywords: :

• hepatitis B
• vaccine
• challenge dose
• persistence
• hepatitis B virus

Disclosure of Potential Conflicts of Interest

Y.P. has received grants from the Thailand Research Fund (DPG5480002), the CU Centenary Academic Development Project and the National Research University Project of Thailand (HR1155A-55) for conducting research and clinical trials. Outside the scope of the submitted work, Y.P. also has received payments from the GlaxoSmithKline group of companies or other pharmaceutical companies for presenting lectures. V.C. and A.T. declare no conflicts of interest; P.C. is employed at GlaxoSmithKline group of companies; M.M. was employed by the GlaxoSmithKline group of companies as a consultant (from the CRO CHILTERN) at the time of this trial; K.H. is employed by the GlaxoSmithKline group of companies and also has stock ownership at the GlaxoSmithKline group of companies.

This study was sponsored and funded by GlaxoSmithKline Biologicals SA. The sponsor was involved in all stages of the study, i.e,. from study design to data analysis and writing of the report. The corresponding author had full access to all the data in the study and had final responsibility for the decision to submit for publication. Authors (Y.P. and A.T.) were supported by the Center of Excellence in Clinical Virology, Chulalongkorn University (CU56-HR01) the Thailand Research Fund (DPG5480002) and the National Research University Fund (HR1155A).

Acknowledgments

We thank the infants and their families for participating in this trial. We also thank all investigators, the study nurses and other staff members of the Center of Excellence in Clinical Virology for contributing in many ways to this study. The authors thank Harshith Bhat for medical writing; Manjula K. and Lakshmi Hariharan for editorial and coordinating support in preparing this manuscript (all employees of the GlaxoSmithKline group of companies).