What Happens If the Third Dose of Hepatitis B Vaccine Is Missed
Simply administer the delayed third dose as soon as possible—the series does not need to be restarted, and protection will be achieved once the dose is given with proper timing intervals. 1
Core Management Principle: Never Restart the Series
The ACIP provides unequivocal guidance that applies to all hepatitis B vaccine schedules: when interrupted at any point, the series is never restarted—you simply continue where you left off. 1 This principle is grounded in immunologic memory, where the immune system retains memory of previous vaccine doses even after extended intervals. 2
Specific Timing Requirements for the Delayed Third Dose
When administering the missed third dose, you must respect these minimum intervals:
- At least 8 weeks after the second dose 1, 3
- At least 16 weeks after the first dose 1, 3
- For infants: not before 24 weeks of age, regardless of when earlier doses were given 1, 3
The 4-day grace period applies (doses given ≤4 days before minimum intervals are valid), except for the accelerated Twinrix schedule. 1, 3
Evidence Supporting Delayed Third Dose Efficacy
The immunologic response to a delayed third dose is actually superior to on-time administration. Research demonstrates that 95.3% of travelers who received their third dose 1-10 years after the second dose achieved seroprotection (anti-HBs >10 IU/L), including 94.1% of those with intervals exceeding 5 years. 4
Additional evidence shows that longer intervals between the second and third doses (4-12 months) result in higher final antibody titers compared to shorter intervals. 5 When the third dose was given at 12 months versus 6 months versus 2 months, geometric mean titers were 19,912 IU/L, 5,846 IU/L, and 53 IU/L respectively—demonstrating the booster effect is enhanced with longer intervals. 5
High-Risk Populations Requiring Urgent Catch-Up
Certain groups should receive the delayed third dose urgently due to ongoing exposure risk:
- Healthcare personnel and public safety workers with potential blood/body fluid exposure 1
- Hemodialysis patients (who require higher doses and annual anti-HBs monitoring) 1
- Household or sexual contacts of HBsAg-positive persons 1
- HIV-infected persons and other immunocompromised individuals 1
- Persons born in countries with HBV endemicity ≥2% 2
Post-Vaccination Serologic Testing
For the high-risk groups listed above, measure anti-HBs levels 1-2 months after completing the delayed third dose. 1 Seroprotection is defined as anti-HBs ≥10 mIU/mL. 1, 3 If non-response occurs (anti-HBs <10 mIU/mL), consider revaccination with an alternative vaccine or high-dose formulation. 2
For average-risk individuals, post-vaccination testing is not routinely recommended. 1
Common Pitfalls to Avoid
- Do not restart the series even if years have passed—this wastes vaccine and delays protection 1, 2
- Do not give the third dose before 16 weeks from the first dose, even if 8 weeks have passed since the second dose 3
- Do not administer inadequate doses or use shorter-than-recommended intervals, as these must be readministered 1
- For infants, do not give the final dose before 24 weeks of age, as this may compromise long-term immunity 1, 3
Special Vaccine-Specific Considerations
For Twinrix (combination hepatitis A/B): If using the accelerated 4-dose schedule (0,7,21-30 days, 12 months), the final 12-month dose is crucial for long-term immunity and should be administered as soon as possible if delayed. 6 The standard 4-day grace period does not apply to the first three doses of this accelerated schedule. 1, 6
For Heplisav-B (2-dose series): This applies only to adults ≥18 years with a 0 and 1-month schedule, so a "third dose" scenario does not apply. 1