In an adult who has completed the hepatitis B vaccine series and now has a non‑protective anti‑hepatitis B surface antibody titer (<10 mIU/mL), should a single booster dose be given or should the entire series be repeated?

Management of Low Anti-HBs Titers After Hepatitis B Vaccination

For an adult who completed the hepatitis B vaccine series and now has anti-HBs <10 mIU/mL, give a single booster dose first, then retest 1-2 months later—do not immediately repeat the entire series. 1

Initial Management Algorithm

• Healthcare personnel and other high-risk individuals with documented complete vaccination but anti-HBs <10 mIU/mL should receive one additional standard dose of hepatitis B vaccine, followed by anti-HBs testing 1-2 months after the booster dose. 1, 2

• Between 60-97% of initial non-responders will achieve protective levels (≥10 mIU/mL) after a single booster dose. 2

• If anti-HBs remains <10 mIU/mL after the single booster dose, then proceed with a complete second 3-dose series using the standard 0,1, and 6-month schedule. 1, 2, 3

When to Proceed with Full Revaccination Series

• Only administer a complete second 3-dose series if the single booster dose fails to produce anti-HBs ≥10 mIU/mL at 1-2 months post-booster. 1, 3

• Among initial non-responders who receive a complete second series, 44-100% will achieve protective antibody levels. 1, 4

• Retest anti-HBs 1-2 months after the third dose of the second series. 1, 4

Management After Second Complete Series

• If anti-HBs remains <10 mIU/mL after two complete 3-dose series (6 total doses), test for HBsAg and anti-HBc to rule out chronic hepatitis B infection. 3, 4

• Persons who remain non-responsive after 6 total doses should not receive additional vaccine doses, as further vaccination is not recommended and will not help. 3

• Confirmed non-responders require hepatitis B immune globulin (HBIG, 0.06 mL/kg) for any known HBsAg-positive exposure, with the first dose given as soon as possible (preferably within 24 hours) and a second dose 1 month later. 3, 4

Special Population Considerations

• Hemodialysis patients require annual anti-HBs monitoring and should receive a 40 mcg booster dose when levels decline below 10 mIU/mL. 2, 3

• Immunocompromised persons (HIV-infected, transplant recipients, chemotherapy patients) should consider annual anti-HBs testing if ongoing exposure risk exists and receive boosters when levels fall below 10 mIU/mL. 2, 3

• Modified dosing regimens with doubled antigen doses (40 mcg instead of 20 mcg) may increase response rates in immunocompromised patients. 4

Important Context About Immune Memory

• Immunocompetent individuals who achieved anti-HBs ≥10 mIU/mL after the primary series maintain long-term protection through immune memory, even when antibody levels decline below detectable levels. 2, 5

• Studies demonstrate that 88-90% of persons maintain immune memory even 30-35 years after vaccination, responding appropriately to challenge doses. 6, 7

• However, for healthcare personnel and other high-risk groups with ongoing exposure risk, documented antibody levels ≥10 mIU/mL remain the standard for confirming protection. 1, 3

Critical Pitfalls to Avoid

• Do not immediately administer a full 3-dose series without first trying a single booster dose—this wastes resources and is not supported by current guidelines. 1, 2

• Do not assume a patient is a non-responder without confirming they completed the full primary series with appropriate intervals (minimum 4 weeks between doses 1 and 2,8 weeks between doses 2 and 3, and 16 weeks between doses 1 and 3). 4

• Do not administer more than 6 total doses (two complete 3-dose series) to non-responders, as additional doses beyond this are not recommended. 3

• Do not rely on patient recall alone for vaccination history—only accept dated records as evidence of vaccination. 2