Durability of antibody response against hepatitis B virus in healthcare workers vaccinated as adults

Abstract

Background: Follow-up studies of recipients of hepatitis B vaccine from endemic areas have reported loss of antibody to hepatitis B surface antigen (anti-HBs) in a high proportion of persons vaccinated at birth. In contrast, the long-term durability of antibody in persons vaccinated as adults in nonendemic areas is not well defined. We aimed to assess the durability of anti-HBs among healthcare workers (HCWs) vaccinated as adults and response to a booster among those without protective levels of antibody.

Methods: Adult HCWs aged 18-60 at the time of initial vaccination were recruited. All were tested for hepatitis B surface antigen (HBsAg), antibody to hepatitis B core antigen (anti-HBc), and anti-HBs level. HCWs with anti-HBs <12 mIU/mL were offered a booster and levels were measured 1, 7, and 21 days afterward.

Results: Anti-HBs levels were <12 mIU/mL in 9 of 50 (18%), 13 of 50 (26%), and 14 of 59 (24%) HCWs 10-15, 16-20, and >20 years postvaccination, respectively, (P = ns). Four HCWs were anti-HBc positive; none had HBsAg. By logistic regression, older age at vaccination was the only predictor of inadequate anti-HBs level (P = .0005). Thirty-four of 36 subjects with inadequate anti-HBs levels received a booster and 32 (94%) developed levels >12 mIU/mL within 3 weeks.

Conclusions: Anti-HBs levels decrease after 10-31 years and fall below a level considered protective in approximately 25% of cases. The rapid and robust response to a booster vaccine suggests a long-lasting amnestic response. Hepatitis B vaccination provides long-term protection against hepatitis B and booster vaccination does not appear to be necessary in HCWs. Clinical Trials Registration. NCT01182311.

Keywords: booster vaccination; chronic hepatitis B; healthcare workers; hepatitis B vaccine.

Figure 1.

Study design and major findings. Flowchart indicates number of subjects screened and included in the study. Thirty-six of 159 subjects had antibody to hepatitis B surface antigen (anti-HBs) levels <12 mIU/mL (group 1, 9/50 [18%]; group 2, 13/50 [26%]; and group 3, 14/59 [24%]). Thirty-four of 36 received a booster vaccine (group 1, 8/9 [88%]; group 2, 12/13 [92%]; and group 3, 14/14 [100%]). Thirty-two of 34 developed protective levels of anti-HBs 3 weeks after the booster vaccine (group 1, 7/8 [86%]; group 2, 11/12 [92%]; and group 3, 14/14 [100%]). Abbreviation: HBV, hepatitis B virus.

Figure 2.

A, Box plots showing distribution of antibody to hepatitis B surface antigen (anti-HBs) levels among subjects in the 3 groups. There was no difference in anti-HBs levels among the 3 groups: group 1 (10–15 years since vaccination), 811 mIU/mL; group 2 (16–20 years since vaccination), 321 mIU/mL; and group 3 (>20 years since vaccination), 371 mIU/mL (P = .1). Average, 25th and 75th percentiles, and range are shown. B, Change in anti-HBs levels over time since initial vaccination. There was no correlation between the magnitude of change in anti-HBs level over time (r² = 0.0013, P = .85). Change was calculated based on last anti-HBs level minus initial anti-HBs level usually obtained 9–12 months after first vaccine dose (n = 36).

Figure 3.

Correlation between antibody to hepatitis B surface antigen (anti-HBs) levels and age at vaccination. There was an inverse correlation between anti-HBs levels and age at vaccination. Older age at vaccination is a significant predictor of inadequate anti-HBs level (r² = 0.069, P = .0008).