Timing of the Second Hepatitis B Vaccination
The second hepatitis B vaccination should be administered at least 1 month (4 weeks minimum) after the first dose. 1, 2
Standard Timing Schedules
For Infants Born to HBsAg-Negative Mothers
- First dose: At birth or by 2 months of age 1
- Second dose: At 1-2 months of age (minimum 4 weeks after first dose) 1
- Third dose: At 6 months of age 1
For Infants Born to HBsAg-Positive Mothers
- First dose: Within 12 hours of birth (with HBIG) 1
- Second dose: At 1-2 months of age 1
- Third dose: At 6 months of age 1
For Adolescents and Adults (Standard 3-Dose Series)
Minimum Interval Requirements
The Advisory Committee on Immunization Practices establishes clear minimum intervals that must be respected: 1, 2
- Between dose 1 and dose 2: Minimum 4 weeks 1, 2
- Between dose 2 and dose 3: Minimum 8 weeks 1, 2
- Between dose 1 and dose 3: Minimum 16 weeks 1, 2
Grace Period Rule
- Doses administered ≤4 days before the minimum interval are considered valid and do not need to be repeated 2, 3
- Doses given more than 4 days early must be readministered 1
Management of Interrupted Schedules
If the second dose is delayed beyond the recommended timing, the series should never be restarted—simply continue where you left off. 1, 2, 3
- Administer the delayed second dose as soon as possible 1, 2
- Maintain the minimum 4-week interval from the first dose 1, 2
- The third dose should then follow at least 8 weeks after this delayed second dose 1, 2
This principle is based on immunologic memory, which retains the effect of previous vaccine doses even with extended intervals. 3
Special Vaccine Formulations
Heplisav-B (2-Dose Series for Adults ≥18 Years)
Twinrix (Combination Hepatitis A/B)
Common Pitfalls to Avoid
- Do not restart the series if the second dose is delayed—this wastes vaccine and delays protection 2, 3
- Do not give the second dose earlier than 4 weeks after the first dose (except within the 4-day grace period) 1, 2
- Do not use inadequate doses or shorter intervals, as these must be readministered 1, 3
High-Risk Populations Requiring Urgent Vaccination
The following groups should receive their second dose urgently if delayed: 2, 3, 4
- Healthcare personnel with potential blood/body fluid exposure 4
- Hemodialysis patients 2, 4
- Household or sexual contacts of HBsAg-positive persons 2, 3
- HIV-infected persons and other immunocompromised individuals 2, 4
- Persons born in countries with HBV endemicity ≥2% 3, 4
- Men who have sex with men 2
- Current or past persons who inject drugs 2