What should be done if the first dose of the hepatitis B (HB) vaccine is missed?

Management of Missed First Dose of Hepatitis B Vaccine

If the first dose of the hepatitis B vaccine is missed, simply administer it as soon as possible and continue the series without restarting—the vaccine schedule does not need to be restarted regardless of the delay. 1, 2

Core Principle: Never Restart the Series

The Advisory Committee on Immunization Practices (ACIP) provides clear guidance that applies universally to all hepatitis B vaccine schedules:

• When any hepatitis B vaccine schedule is interrupted, the series does not need to be restarted. 1, 2
• The delayed first dose should be administered as soon as possible, and subsequent doses should follow the appropriate intervals from that point. 1, 2
• This principle is based on immunologic memory—the immune system retains memory of previous vaccine doses even with extended intervals between doses. 2

Recommended Dosing Intervals After Late First Dose

Once the first dose is administered (regardless of delay), follow these minimum intervals:

• The second dose should be given at least 4 weeks after the first dose. 1
• The third dose must be administered at least 8 weeks after the second dose. 1
• The third dose should follow the first dose by at least 16 weeks total. 1
• Doses administered ≤4 days before the minimum interval are considered valid. 1

Special Considerations by Vaccine Type

Standard 3-Dose Series (Engerix-B, Recombivax HB)

• Schedule: 0,1, and 6 months 1
• If only starting now, give the first dose immediately, second dose 1 month later, and third dose 6 months after the first dose. 1

Heplisav-B (2-Dose Series)

• Schedule: 0 and 1 month for adults ≥18 years 2
• If the first dose is delayed, give it immediately and the second dose 1 month later. 2
• Even if the interval exceeds 1 month, do not restart—simply complete the series. 2

Twinrix (Combination Hepatitis A/B)

• Accelerated schedule: 0,7,21-30 days, and 12 months 3
• The 4-day grace period does not apply to the first 3 doses of the accelerated schedule. 3
• If delayed, administer the first dose immediately and continue the series. 3

Common Pitfalls to Avoid

• Do not restart the series even if months or years have passed since the intended first dose—this wastes vaccine and delays protection. 1, 2
• Do not give inadequate doses or use shorter-than-recommended intervals between subsequent doses, as these must be readministered. 1
• Do not delay vaccination further while waiting for "optimal timing"—protection begins with the first dose. 1

High-Risk Populations Requiring Urgent Catch-Up

For certain high-risk individuals, initiating the delayed series becomes particularly urgent:

• Healthcare personnel who may have occupational exposure to blood or body fluids 1
• Persons with HIV infection, where vaccine response correlates with viral load and CD4 count 4
• Hemodialysis patients who require higher doses and annual anti-HBs monitoring 1
• Persons born in countries with HBV endemicity ≥2% 1
• Household or sexual contacts of HBsAg-positive persons 1

Post-Vaccination Serologic Testing

After completing the delayed series:

• Test anti-HBs levels 1-2 months after the final dose for high-risk groups including healthcare personnel, hemodialysis patients, HIV-infected persons, and other immunocompromised individuals. 2, 5
• Seroprotection is defined as anti-HBs ≥10 mIU/mL. 5
• If non-response occurs (anti-HBs <10 mIU/mL), consider revaccination with Heplisav-B (90% seroprotection rate) or high-dose Engerix-B (40 μg on 0,1,2,6-month schedule). 5

Evidence Supporting Flexible Timing

Research demonstrates that hepatitis B vaccine response is remarkably robust despite variations in timing:

• Studies show that longer intervals between doses (particularly before the third dose) actually produce higher antibody titers than standard schedules. 6, 7
• A third dose given at 12 months produces geometric mean titers significantly higher than doses given at 6 months. 7
• Overall vaccine response remains excellent (98% seroconversion) even with substantial deviations from recommended schedules. 6