What is the latest recommended Hepatitis B (Hep B) vaccine schedule?

Hepatitis B Vaccine Schedule

Standard Schedule for Most Populations

The CDC recommends the standard hepatitis B vaccination schedule of 3 doses administered at 0,1, and 6 months for infants, children, adolescents, and adults. 1, 2

This schedule achieves seroprotection (anti-HBs ≥10 mIU/mL) in >90% of healthy adults under 40 years and >98% of children and adolescents. 1, 3

Critical Minimum Intervals Between Doses

When administering the hepatitis B vaccine series, strict adherence to minimum intervals is essential:

• Minimum interval between dose 1 and dose 2: 4 weeks 1, 2, 4
• Minimum interval between dose 2 and dose 3: 8 weeks 1, 2, 4
• Minimum interval between dose 1 and dose 3: 16 weeks 1, 2, 4
• For infants: the final dose must not be given before 24 weeks of age, regardless of when earlier doses were administered 1, 4

A 4-day grace period applies—doses given ≤4 days before the minimum interval are considered valid and do not need repeating. 1, 2, 4

Special Population Schedules

Infants Born to HBsAg-Positive Mothers

• First dose must be given within 12 hours of birth plus HBIG 1
• Second dose at 1-2 months 1
• Third dose at 6 months 1
• Post-vaccination testing at 9-15 months for HBsAg and anti-HBs 1

Delaying the birth dose beyond 12 hours significantly increases infection risk. 1

Hemodialysis Patients

• Use 40 μg doses (2 × 20 μg) of Recombivax HB or Engerix-B at 0,1,2, and 6 months (4-dose schedule) 1, 2, 3
• Annual anti-HBs testing with booster doses when levels fall below 10 mIU/mL 1, 2
• Standard adult doses are inadequate for this population 2

Adolescents (Ages 11-15 Years)

• Alternative 2-dose schedule: adult formulation of Recombivax HB at 0 and 4-6 months 2
• Standard 3-dose schedule (0,1,6 months) remains an option 2

Alternative Accelerated Schedules

For situations requiring rapid protection:

• Engerix-B: 0,1,2, and 12 months 1
• Twinrix (for combined hepatitis A and B protection): 0,7, and 21-30 days, followed by a dose at 12 months 1

The accelerated 0,1,2-month schedule achieves 99% seroprotection by month 3, but the fourth dose at 12 months is essential for optimal long-term immunity. 3, 5

Interrupted Vaccination Series

If the vaccination series is interrupted at any point, never restart the series—simply continue where you left off. 1, 2, 4

• Give dose 2 as soon as possible if interrupted after dose 1, maintaining at least 4 weeks from dose 1 4
• Give dose 3 at least 8 weeks after dose 2 and at least 16 weeks after dose 1 4

Restarting wastes doses and delays protection. 1

Immunogenicity by Schedule

The interval between doses significantly impacts antibody response:

• After dose 1: 30-55% achieve protective levels 1
• After dose 2: 75% achieve protection 1
• After dose 3: >90% achieve protection 1

Longer intervals between the last two doses result in higher final antibody titers. 1, 5 The 0,1,12-month schedule produces higher GMTs (19,912 IU/L) compared to 0,1,6-month (5,846 IU/L) or 0,1,2-month (53 IU/L) schedules. 5

Pregnancy Considerations

• Use only Engerix-B, Recombivax HB, or Twinrix 1
• Do not use Heplisav-B or PreHevbrio due to insufficient safety data in pregnancy 1

Common Pitfalls to Avoid

• Never restart the series if interrupted—this wastes doses and delays protection 1, 2, 4
• Do not give the third dose before 16 weeks from the first dose, even if 8 weeks have passed since the second dose 1, 4
• Do not give the final infant dose before 24 weeks of age—this may compromise long-term immunity 1, 4
• Do not use standard adult doses in hemodialysis patients—they require 40 μg doses 1, 2
• Do not use Twinrix for hepatitis B vaccination alone when the patient has no indication for hepatitis A protection 1

Age-Related Response

Response rates decline with age—adults over 40 years achieve lower antibody titers (GMT 610 mIU/mL) compared to younger adults. 3 Immunocompromised patients and hemodialysis patients require higher doses and more frequent monitoring. 2