Is a third dose of Hepatitis B vaccine (Engerix-B) (Hepatitis B vaccine) due at one month or five months after receiving the first dose of Engerix-B (Hepatitis B vaccine) and the second dose of Hepatitis B vaccine (Dynavax) (Heplisav-B), given that the first dose was part of a three-dose series and the second dose was part of a two-dose series?

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Last updated: May 8, 2025View editorial policy

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From the Guidelines

The patient should receive a third dose of hepatitis B vaccine at 5 months after the second dose, which is consistent with completing the initial three-dose series started with Engerix-B. Since the first dose was Engerix-B (part of a three-dose series) and the second dose was Heplisav-B (Dynavax, normally a two-dose series), the safest approach is to follow through with the three-dose schedule, as recommended by the Advisory Committee on Immunization Practices (ACIP) in 2022 1. This means administering a third dose 5 months after the second dose (or 6 months after the first dose), ensuring adequate immunity development. Mixing different hepatitis B vaccines is not ideal but can still provide protection, and the series does not need to be restarted if interrupted 1. Completing the series is important for long-term protection against hepatitis B infection. The patient should be advised that despite the mixed vaccines, completing the full series will likely provide effective immunity against hepatitis B virus. Key points to consider include:

  • The minimum interval between the first and second doses is 4 weeks, and between the second and third doses is 8 weeks 1.
  • Inadequate doses of hepatitis B vaccine or doses received after a shorter-than-recommended dosing interval should be readministered, using the correct dosage or schedule 1.
  • The final dose of a 3-dose series must be administered ≥8 weeks after the second dose and ≥16 weeks after the first dose 1.

From the FDA Drug Label

Interchangeability With Other Hepatitis B Vaccines: ...it should be possible to interchange the use of ENGERIX-B and plasma-derived vaccines... A controlled study (N = 48) demonstrated that completion of a course of immunization with 1 dose of ENGERIX-B (20 mcg, month 6) following 2 doses of RECOMBIVAX HB® * (10 mcg, months 0 and 1) produced a similar GMT (4,077 mIU/mL) to immunization with 3 doses of RECOMBIVAX HB (10 mcg, months 0,1, and 6; 2,654 mIU/mL).

The patient received the first dose of ENGERIX-B and the second dose with Dynavax. The FDA drug label does not provide direct information on the interchangeability of ENGERIX-B with Dynavax. However, based on the information provided, it is not possible to determine the next dose due date. The patient's vaccination schedule is unclear, and the FDA drug label does not provide guidance on this specific situation 2, 2, 2.

From the Research

Hepatitis B Vaccination Schedule

The user has received the first dose of Engerix-B and the second dose of Heplisav-B (Dynavax), which are both hepatitis B vaccines with different dosing schedules.

  • Engerix-B is a three-dose regimen over a 6-month time period 3.
  • Heplisav-B is a two-dose regimen over 1 month 3, 4.

Determining the Next Dose

Since the user has already received one dose of Engerix-B and one dose of Heplisav-B, the next dose due would depend on the completion of the initial vaccine series.

  • If the user is to complete the Engerix-B series, the next dose would be due at 5 months after the first dose, considering the standard 6-month time period for the three-dose regimen 3.
  • However, since the user received the second dose as Heplisav-B, which is a two-dose regimen, it is unclear whether the user would require a third dose at 1 month or 5 months.

Available Research

There is limited research available to directly answer this question, as the studies primarily compare the efficacy and safety of Engerix-B and Heplisav-B in different populations, rather than addressing mixed vaccine regimens 5, 6, 7.

  • One study suggests that a two-dose regimen of hepatitis B vaccine can induce an antibody response similar to the standard three-dose regimen 5.
  • Another study compares the seroprotection rates of Engerix-B and Heplisav-B in patients receiving maintenance dialysis, but does not address mixed vaccine regimens 6.

References

Guideline

Guideline Directed Topic Overview

Dr.Oracle Medical Advisory Board & Editors, 2025

Research

CpG-Adjuvanted Hepatitis B Vaccine (HEPLISAV-B®) Update.

Expert review of vaccines, 2021

Research

A real world comparison of HepB (Engerix-B®) and HepB-CpG (Heplisav-B®) vaccine seroprotection in patients receiving maintenance dialysis.

Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association, 2023

Research

Heplisav-B: A Hepatitis B Vaccine With a Novel Adjuvant.

The Annals of pharmacotherapy, 2021

Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

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