Durability of immunity by hepatitis B vaccine in Japanese health care workers depends on primary response titers and durations

Abstract

Background: Health care workers (HCWs) are frequently exposed to hepatitis B virus (HBV) infection. The efficacy and safety of immunization with the hepatitis B (HB) vaccine are well recognized, but the durability of immunity and need for booster doses in those with secondary vaccine response failure remains controversial.

Methods: This was a retrospective cohort study performed at Osaka University Hospital, Japan. We examined antibodies against HB surface antigen (anti-HBs) titers annually after immunization for previously non-immunized HCWs. Primary responders were categorized by their sero-positive durations as short responders (those whose anti-HBs titers declined to negative range within 3 years), and long responders (those who retained positive anti-HBs levels for 3 years and more). We re-immunized short responders with either single or 3-dose boosters, the long responders with a single booster when their titers dropped below protective levels, and examined their sero-protection rates over time thereafter.

Results: From 2001 to 2012, data of 264 HCWs with a median age of 25.3 were collected. The rate of anti-HBs positivity after primary vaccination were 93.0% after three doses (n = 229), 54.5% after two doses (n = 11), and 4.2% after a single dose (n = 24). Of 213 primary responders, the anti-HBs levels of 95 participants (44.6%) fell below the protective levels, including 46 short responders and 49 long responders. HCWs with higher initial anti-HBs titers after primary vaccination had significantly longer durations of sero-positivity. For short responders, 3-dose booster vaccination induced a longer duration of anti-HBs positivity compared to a single-dose booster, whereas for long responders, a single-dose booster alone could induce prolonged anti-HBs positivity.

Conclusion: Our preliminary data suggested that it may be useful to differentiate HB vaccine responders based on their primary response durations to maintain protective levels of anti-HBs efficiently. A randomized, prospective, large-scale study is warranted to support our findings.

Fig 1. Flow of the study.

Individuals who retained positive anti-HBs titers for >3 years were regarded as long responders and those who did not were regarded as short responders.

Fig 2. Doses of primary hepatitis B vaccine and rate of anti-HBs positivity.

Fig 3. Initial anti-HBs titers of primary responders after full series of vaccination and its duration of positivity.

(A) A box indicates a median and interquartile range, and error bars denote the 10th and 90th percentiles. (B) High (> 500 mIU/mL, n = 35), moderate (100–500 mIU/mL, n = 62), and low (< 100 mIU/mL, n = 46) titers. It was a significant trend that individuals with lower titers of initial anti-HBs experienced secondary vaccine response failure earlier.

Fig 4. Booster doses administered to short/long responders and duration of anti-HBs positivity.