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What is the difference between Heplisav-B and Engerix-B?

Medically reviewed by Leigh Ann Anderson, PharmD. Last updated on May 17, 2023.

Official answer


Heplisav-B is the only two-dose hepatitis B vaccine approved for adults. Engerix-B requires three shots over a six-month period.

Heplisav-B and Engerix-B are both recombinant hepatitis B vaccines given by intramuscular (IM) injection, but Heplisav-B, approved in November 2017, contains an adjuvant, an agent that can help to boost the immune response to the vaccine. Hepatitis B vaccination is the primary way to prevent infections and complications caused by hepatitis B virus.

Heplisav-B, made by Dynavax, combines hepatitis B surface antigen (HBsAg) with a proprietary adjuvant known as 1018. This activates Toll-like Receptor 9 (TLR9) agonist to enhance the immune response. In turn, a highly specific, helper T-cell response may generate memory T and B cells.

Engerix-B, from GSK, does not contain an adjuvant. It is formulated as a suspension of the antigen adsorbed on aluminum hydroxide

Can Heplisav-B be used in children?

  • Heplisav-B is only approved for prevention of hepatitis B virus in adults age 18 years and older.
  • Engerix-B is used in both pediatrics, starting with infants at birth, and adults.

How is Heplisav-B given?

Most current hepatitis B vaccines require three shots over a six-month period, however, almost half of adults fail to complete the series within one year. With Heplisav-B, a two-dose series given one month apart may help to increase the vaccine completion rates.

How does Heplisav-B compare to Engerix-B?

Higher rates of effectiveness in adults were shown with Heplisav-B vaccine when compared to Energix.

  • In Phase III studies, Heplisav-B was administered in two doses over one month and compared to Engerix-B administered in three doses over a six-month schedule.
  • Heplisav-B demonstrated a statistically significantly higher rate of protection (95%) after one month when compared with Engerix-B (81%) after 6 months.
  • In a subgroup analysis in patients with Type 2 diabetes, Heplisav-B demonstrated a statistically significantly higher rate of protection of 90% compared to 65% for Engerix-B.

In April 2018, the Advisory Committee on Immunization Practices (ACIP) recommended the use of Heplisav-B for protecting adults 18 years and older at risk of hepatitis B infection.

Do the side effects with Heplisav-B differ from Engerix-B?

Types of side effects appear to be similar between the two vaccines.

  • Across the three clinical trials with Heplisav-B, the most common side effects were injection site pain (23% to 39%), fatigue (11% to 17%) and headache (8% to 17%).
  • With Engerix-B, common side effects included injection-site soreness (22%), fatigue (14%), headache and dizziness (1% to 10%).

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