Hepatitis B Vaccination Schedules
Standard Adult Schedules (≥18 years)
For adults aged 19-59 years, use the 2-dose Heplisav-B series (0 and 1 month) as the preferred option, or alternatively a 3-dose traditional vaccine series (0,1, and 6 months) with Engerix-B, Recombivax HB, or PreHevbrio. 1, 2, 3
Available Adult Vaccine Options:
- Heplisav-B (preferred): 20 μg (0.5 mL) at 0 and 1 month (minimum 4 weeks apart) 4, 1, 2
- Recombivax HB: 10 μg (1.0 mL) at 0,1, and 6 months 1, 2
- Engerix-B: 20 μg (1.0 mL) at 0,1, and 6 months 1, 2
- PreHevbrio: 10 μg (1.0 mL) at 0,1, and 6 months 2
- Twinrix (combined HepA/HepB): Standard schedule at 0,1, and 6 months OR accelerated schedule at 0 days, 7 days, 21-30 days, and 12 months 2
The 2-dose Heplisav-B offers superior compliance due to fewer visits and shorter completion time, while achieving >90% seroprotection in healthy adults <40 years. 2, 5
Infant Vaccination
All infants must receive the first hepatitis B vaccine dose at birth, with series completion by 6-18 months of age. 1
Critical Timing Requirements:
- First dose: Within 24 hours of birth 1
- Series completion: By 6-18 months of age 1
- Final dose timing: Must be administered at ≥24 weeks of age (this is non-negotiable) 1, 2
If a combination vaccine (DTaP-IPV-Hib-HepB) is inadvertently given before 24 weeks as the third dose, you must administer an additional monovalent hepatitis B vaccine dose at ≥24 weeks. 1
Pregnant Women
Pregnant women requiring hepatitis B vaccination must receive only Engerix-B, Recombivax HB, or Twinrix—never Heplisav-B or PreHevbrio. 4, 1, 2
This restriction exists because Heplisav-B and PreHevbrio lack safety data in pregnancy. 4, 1, 2 Use the standard 3-dose schedule at 0,1, and 6 months with the approved vaccines. 2
Hemodialysis Patients
Hemodialysis patients require high-dose formulations with enhanced schedules due to impaired immune response. 1, 2
Dosing Options:
- Recombivax HB: 40 μg (1.0 mL) at 0,1, and 6 months (3-dose series) 1, 2
- Engerix-B: 40 μg (2.0 mL) at 0,1,2, and 6 months (4-dose series) 1, 2
Do not use Heplisav-B or PreHevbrio in hemodialysis patients. 1, 2
Post-Vaccination Monitoring:
- Test anti-HBs 1-2 months after series completion 4, 2
- Perform annual anti-HBs testing thereafter 4
- Administer booster doses when anti-HBs declines to <10 mIU/mL 4
- Do not retest anti-HBs after booster doses 4
Even with high-dose regimens, only 67% of hemodialysis patients achieve seroprotection (compared to >90% in healthy adults), reflecting their profoundly impaired immune response. 2
Immunocompromised Adults (Non-Dialysis)
For immunocompromised adults ≥20 years (including HIV-infected persons, transplant recipients, and those on chemotherapy), use high-dose formulations. 1, 2
Dosing Options:
- Recombivax HB: 40 μg (1.0 mL) at 0,1, and 6 months 2
- Engerix-B: 40 μg (2.0 mL) at 0,1,2, and 6 months 2
For HIV-infected adults specifically, the Infectious Diseases Society of America recommends either 40 μg Recombivax HB (3-dose) or 40 μg Engerix-B administered as two simultaneous 20 μg injections (4-dose schedule at 0,1,2, and 6 months). 2
Post-Vaccination Management:
- Test anti-HBs 1-2 months after series completion 4, 2
- Consider annual anti-HBs testing and booster doses for those with ongoing exposure risk 4
Do not use Heplisav-B or PreHevbrio in immunocompromised patients. 1, 2
Accelerated Schedules for Rapid Protection
When rapid seroprotection is needed (e.g., recent exposure, imminent travel), use an accelerated 4-dose schedule at 0,1,2, and 12 months. 1, 6, 7
This accelerated schedule achieves earlier seroconversion after 3 doses, but the fourth dose at 12 months is mandatory for long-term protection. 1, 6, 7 After the third dose at month 2, antibody levels (GMT 53 IU/L) are substantially lower than with standard schedules, but the fourth dose at month 12 produces a robust booster response comparable to standard schedules. 7
Alternative Accelerated Option:
For combined hepatitis A and B protection, Twinrix can be given on a super-accelerated schedule: 0 days, 7 days, 21-30 days, and 12 months. 1, 2 The 4-day grace period for minimum intervals does not apply to the first 3 doses of this specific schedule. 4
Adolescent Schedules (Ages 11-19)
For adolescents aged 11-15 years, Recombivax HB offers a unique 2-dose option: 10 μg (0.5 mL) at 0 and 4-6 months. 2
Alternatively, use the standard 3-dose schedule (0,1,6 months) with either Recombivax HB 10 μg or Engerix-B 10 μg. 2 For adolescents aged 16-19 years, use adult dosing. 2
Managing Interrupted Schedules
Never restart a hepatitis B vaccine series, regardless of how much time has elapsed—simply continue where you left off. 4, 1, 2
Minimum Interval Requirements:
- Between doses 1 and 2: 4 weeks 4, 1, 2
- Between doses 2 and 3: 8 weeks 4, 1, 2
- Between doses 1 and 3: 16 weeks 4, 1, 2
- Final dose after second dose: ≥8 weeks 4, 1
Doses administered ≤4 days before the minimum interval are considered valid. 4, 2 There is no maximum interval between doses. 1
Switching Vaccine Brands:
When feasible, use the same manufacturer's vaccine throughout the series, but switching brands is acceptable and does not require restarting the series. 4, 1 However, for Heplisav-B to count as a valid 2-dose series, both doses must be Heplisav-B with ≥4 weeks between them. 4
Post-Vaccination Serologic Testing
Routine post-vaccination testing is not recommended for most adults, but is mandatory for specific high-risk groups. 2, 3
Groups Requiring Post-Vaccination Testing:
- Healthcare personnel and public safety workers with blood exposure risk 4, 1, 2
- Hemodialysis patients 4, 2
- Immunocompromised persons 4, 2
- Sex partners of HBsAg-positive persons 3
Test anti-HBs 1-2 months after completing the series. 4, 1, 2 Protective level is ≥10 mIU/mL. 4, 1, 2
Management of Non-Responders (Anti-HBs <10 mIU/mL):
For healthcare personnel with anti-HBs <10 mIU/mL after the first complete series, administer a second complete series (typically 6 total doses), then retest anti-HBs 1-2 months after the final dose. 4, 1 For other adults, consider administering a 2-dose Heplisav-B series or high-dose Engerix-B series. 3
Pre-Vaccination Serologic Testing
Pre-vaccination testing is not required and should never be a barrier to vaccination. 4, 2, 3
However, testing for HBsAg, anti-HBs, and anti-HBc may be considered in populations with high rates of previous HBV infection, including persons born in countries with HBV endemicity ≥2%, household/sexual/needle contacts of HBsAg-positive persons, and persons who inject drugs. 4, 3 When testing is performed, administer the first vaccine dose immediately after blood collection—do not wait for results. 4
Age-Related Considerations
Vaccine response declines significantly with age, affecting schedule selection and expectations. 2
- **Adults <40 years:** >90% achieve protective antibody levels 2, 3
- Adults ≥40 years: 88% achieve protective levels 3
- Adults ≥60 years: Only 75% achieve protective levels 2
Other factors reducing vaccine response include smoking, obesity, and immunosuppression. 2 Despite declining antibody levels over time, immunocompetent individuals who achieve anti-HBs >10 mIU/mL after vaccination have virtually complete protection against chronic infection, even if antibodies subsequently decrease. 1
Common Pitfalls to Avoid
- Do not restart interrupted series—there is no maximum interval between doses 4, 1, 2
- Do not use Heplisav-B or PreHevbrio in pregnant women, hemodialysis patients, or children 1, 2
- Do not administer the final infant dose before 24 weeks of age 1, 2
- Do not require pre-vaccination testing as a barrier to vaccination 4, 2, 3
- Do not give booster doses to immunocompetent children—current data do not support this practice 1
- Do not forget the fourth dose at 12 months when using accelerated schedules 1, 6, 7