Long-term Protection After Hepatitis B Vaccine.

Hepatitis B virus (HBV) infection is highly prevalent around the globe. An estimated 3.6% of the world’s population (or 248 million persons) are positive for hepatitis B surface antigen (HBsAg) [1], and HBV causes significant morbidity and mortality. In 2013, approximately 686 000 HBV-infected persons died from causes related to acute infection (69 000 deaths), cirrhosis (317 000 deaths), and HBV-associated liver cancer (300 000 deaths) [2]. The age of acquisition of HBV infection is the main determining factor in the clinical expression of acute disease and the development of chronic infection. Genetic characteristics of HBV might also contribute to the outcome of infection [3, 4]. Safe and effective hepatitis B vaccines have been commercially available since 1982, and, over the years, recombinant DNA vaccines have replaced plasmaderived vaccines. Gaps in hepatitis B vaccination policy were first addressed in 1992, when the World Health Organization called for all countries to incorporate hepatitis B vaccination into their national childhood immunization services. In the following decade, hepatitis B vaccination coverage grew rapidly, and by the end of 2014, 184 countries had integrated hepatitis B vaccine into their national childhood immunization systems, and the global coverage with 3 doses of hepatitis B vaccines was estimated at 82% [5]. Elimination of HBV transmission is an achievable public health goal, particularly in light of the proven effectiveness and safety of hepatitis B vaccine. In general, studies conducted in areas with high HBV endemicity have demonstrated declines in the prevalence of chronic HBV among children to <2% after routine infant immunization [6]. After several decades of hepatitis B vaccination, the duration of protection is still unknown, and the question whether a booster dose is ever needed continues to challenge us. In fact, the hepatitis B vaccine was the first vaccine for which long-term protection was rigorously studied; this was perhaps because of the originally higher cost compared with other infant vaccines or—at least in industrialized countries—owing to the implementation at a younger age although risk exposure would start in adolescence or adulthood. Today, equal attention is given to long-term protection induced by other vaccines, not the least for HPV vaccines. An antibody to hepatitis B surface antigen (anti-HBs) concentration of ≥10 mIU/mL measured 1–3 months after administration of the last dose of the initial vaccination series is considered a reliable marker of protection against infection [7]. After primary hepatitis B immunization, anti-HBs concentrations decline rapidly within the first year and more slowly thereafter: among children who respond to a primary 3-dose vaccination series with anti-HBs concentrations of ≥10 mIU/mL, 15%–50% have low or undetectable concentrations of anti-HBs 5– 15 years after vaccination; among adult vaccinees, anti-HBs concentrations decline to <10 mIU/mL in 7%–50% within 5 years after vaccination and in 30%–60% within 9–11 years [8]. The persistence of anti-HBs over time is correlated with the peak level of anti-HBs immediately achieved after primary immunization [9]. In other words, the higher the vaccine-induced anti-HBs concentration after the primary vaccination course, the longer the antibodies will persist. The issue of duration of protection can be addressed, as documented in by Bruce et al [10] in this issue of The Journal of Infectious Diseases, by long-term followup studies of immunized cohorts who continue to be exposed to HBV and by exploring anamnestic responses to HBsAg through challenge. Several observational studies have shown that a primary hepatitis B vaccination series can prevent infection for >20 years, despite decrease or loss of vaccine-induced anti-HBs over time [11–16]. Bruce et al [10]present for the first time results of a 30-year follow-up study and response to a booster dose in an Alaskan Native population. It is the longest cohort study on extended protection after hepatitis B vaccination to date. Their unique data add a new piece of evidence to the puzzle of longterm immunity: no significant breakthrough infections were diagnosed in the vaccinees during the 30-year period, and 51% (125 of 243) still had anti-HBs levels ≥10 mIU/mL 30 years after initial vaccine administration [10]. Initial antiHBs level and age at vaccination seemed Received and accepted 10 December 2015; published online 21 January 2016. Correspondence: P. V. Damme, Centre for the Evaluation of Vaccination, Vaccine & Infectious Disease Institute, Antwerp University, Belgium (pierre.vandamme@ua.ac.be). The Journal of Infectious Diseases 2016;214:1–3 © The Author 2016. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail journals.permissions@oup.com. DOI: 10.1093/infdis/jiv750