Do you care for adult patients? If yes, do you routinely offer hepatitis B vaccine?

In 2022, the Centers for Disease Control and Prevention (CDC) recommended routine vaccination of adults up to 59 years of age and those 60 years and older at increased risk. The updated recommendations also indicate that those 60 and older who wish to protect themselves against hepatitis B can be vaccinated.

These recommendations were made based on recent data:

  • More than half of acute cases in 2019 were in those 30 to 49 years of age.
  • Over the last several years, rates of hepatitis B have been increasing in those 40 years of age and older.
  • Vaccination rates in adults are low, even if individuals are at increased risk of hepatitis B.
  • Some adult conditions, like chronic liver disease, decrease vaccine effectiveness.

Recently, a new option for hepatitis B vaccination of adults became available, PreHevbrio™. As adult healthcare providers increase efforts to protect their patients against hepatitis B, we thought it would be useful to describe how this vaccine differs from previously available hepatitis B vaccine options.

A little virology on the way to discussing the active ingredients

Hepatitis B virus famously tricks the immune system by manufacturing extra surface proteins that flood the bloodstream. By doing this, many antibodies bind to the excess surface protein, allowing whole viral particles to remain free to infect other cells. Indeed, Dr. Hilleman used this fact to create the first hepatitis B vaccine, isolated from the blood of infected individuals.

Because making a vaccine from the blood of hepatitis B-positive individuals limited its acceptance, Dr. Hilleman made a second hepatitis B vaccine using genetic engineering. It’s the approach still used today. Specifically, the gene for the surface protein was inserted into yeast cells, so as the yeast reproduced, the hepatitis B protein was also produced. Indeed, all previously approved hepatitis B vaccines approved for use in adults (Engerix-B®, Heplisav-B®, and Recombivax HB®) are made this way.

But the surface protein of hepatitis B virus is complex in that it appears in three sizes: small, medium and large. The small version is made from 226 residues (in proteins a residue is a single amino acid), and it is the version used in existing vaccines. An additional 55-residue portion is known as pre-S2, and when combined with the small version residues, it makes the medium size surface protein. Finally, the largest surface protein includes both portions as well as an additional 108 or 119 residues, called pre-S1. PreHevbrio contains all three differently sized proteins (small, pre-S2 and pre-S1). When this vaccine is made, the proteins are produced in mammalian cells rather than yeast cells.

What else is in the vial?

PreHevbrio contains an aluminum adjuvant. Each dose also contains a series of salts, water, and very small amounts of materials that remain from the manufacturing process, including proteins and DNA from the mammalian cells used to grow the virus, serum albumin (of bovine origin), and formaldehyde.

Other hepatitis B vaccines used in adults also include an aluminum-based adjuvant except for Heplisav-B, which contains a novel adjuvant, called CpG 1018. The “C” stands for cytosine, and the “G” stands for guanine. The “p” stands for the phosphodiester linkage that links the two nucleotides. Nucleotides are the building blocks of DNA.


PreHevbrio was compared with Engerix-B in clinical trials. Seroprotection was defined by the presence of antibodies against hepatitis B surface protein that were greater than or equal to 10 mIU/mL four weeks after the last dose. PreHevbrio seroconversion rates were as good as or slightly better than those of Engerix-B for all age groups evaluated.


All safety profiles for adult hepatitis B vaccine are similar. The most common side effects include pain and redness at the injection site, fatigue, headache and irritability. A small number of people develop mild fever.

PreHevbrio and Heplisav-B are not recommended during pregnancy due to lack of safety data; however, other hepatitis B vaccines can be used if vaccination is needed.

People with history of severe allergic reaction after a previous dose of hepatitis B vaccine should not be vaccinated, and those with severe allergic reactions to yeast should not receive versions grown in yeast cells (Engerix-B, Heplisav-B, and Recombivax HB).

Recommended use

PreHevbrio is recommended for those 18 years and older. It is administered in three doses using a schedule similar to most other hepatitis vaccines. The second dose is given one month after the first, and the third dose is administered six months after the first dose.

Due to the more powerful adjuvant, Heplisav-B requires only two doses separated by one month.

A combination vaccine, known as Twinrix®, contains hepatitis A and hepatitis B components. The hepatitis B component of this vaccine is Engerix-B. Adults who get this vaccine can get three doses at 0, 1 and 6 months or use an accelerated schedule of 0, 7 and 21-30 days. When an accelerated schedule is used, a fourth dose should be administered at 12 months. People with severe allergic reactions to yeast, neomycin, or a previous dose should not receive Twinrix.

Resources for more information

Materials in this section are updated as new information and vaccines become available. The Vaccine Education Center staff regularly reviews materials for accuracy.

You should not consider the information in this site to be specific, professional medical advice for your personal health or for your family's personal health. You should not use it to replace any relationship with a physician or other qualified healthcare professional. For medical concerns, including decisions about vaccinations, medications and other treatments, you should always consult your physician or, in serious cases, seek immediate assistance from emergency personnel.