Delayed Third Dose of Hepatitis B Vaccine in Adults
If the third dose of hepatitis B vaccine is delayed in an adult, simply administer it as soon as possible without restarting the series—the vaccine series never needs to be restarted regardless of how much time has elapsed. 1, 2
Core Management Approach
Do not restart the vaccination series. The Advisory Committee on Immunization Practices is clear that when any hepatitis B vaccine schedule is interrupted at any point, the series does not need to be restarted based on immunologic memory. 2 Simply continue where you left off and administer the delayed third dose as soon as the patient presents. 1, 2
Minimum Interval Requirements When Resuming
When administering the delayed third dose, ensure the following minimum intervals are met:
- At least 8 weeks must have passed since the second dose 1, 2
- At least 16 weeks must have passed since the first dose 1, 2, 3
These intervals are critical and must be respected even if the patient presents earlier than expected. 2
Expected Immune Response with Delayed Dosing
The evidence strongly supports that delayed third doses maintain excellent immunogenicity:
- Research demonstrates that 95.3% of healthy adults achieved seroprotection (anti-HBs >10 IU/L) even when the third dose was delayed a median of 3.4 years after the second dose 4
- Even with intervals exceeding 5 years between the second and third doses, 94.1% of individuals achieved protective antibody levels 4
- Longer intervals between the second and third doses (6-12 months) actually produce higher geometric mean antibody titers compared to shorter intervals 5, 6
Post-Vaccination Serologic Testing
Measure anti-HBs levels 1-2 months after administering the final (third) dose to document seroprotection, defined as anti-HBs ≥10 mIU/mL. 2, 3 This timing is critical—testing performed at other intervals shows lower seroprotection rates:
- Testing at 1-2 months: 98.2% seroprotection 6
- Testing at 3-6 months: 90.6% seroprotection 6
- Testing at ≥7 months: 88.4% seroprotection 6
The lower rates with delayed testing reflect antibody decline over time, not vaccine failure. 6
Priority Populations Requiring Urgent Completion
Certain high-risk adults should resume their delayed series with particular urgency: 2
- Healthcare personnel
- Hemodialysis patients
- Household or sexual contacts of HBsAg-positive persons
- HIV-infected persons and other immunocompromised individuals
- Men who have sex with men
- Current or past persons who inject drugs
For these populations, ongoing exposure risk makes timely completion critical. 2
Management of Non-Responders
If anti-HBs remains <10 mIU/mL after completing the delayed series:
- Administer one additional dose and retest in 1-2 months 2
- If still <10 mIU/mL, complete a second full 3-dose series (6 total doses) and retest 1-2 months after the final dose 2, 3
For hemodialysis patients specifically, perform annual anti-HBs testing and administer booster doses when levels decline to <10 mIU/mL. 2
Common Pitfalls to Avoid
- Never restart the series—there is no maximum interval between doses 2, 3
- Do not administer the third dose before 16 weeks from the first dose, even if 8 weeks have passed since the second dose 2
- Do not test anti-HBs levels before completing all three doses unless assessing response after a complete series 2
- The 4-day grace period for early administration does not apply if you're already past the minimum interval—just give the dose 1, 2