Hepatitis B (HepB) Vaccine

HepB vaccine is produced using recombinant DNA technology. A plasmid containing the gene for hepatitis B surface antigen (HBsAg) is inserted into common baker’s yeast, which then produces HBsAg. The HBsAg is harvested and purified. This vaccine cannot cause hepatitis B virus infection because no potentially infectious viral DNA or complete viral particles are produced during this process.

Several vaccines are available. Two individual recombinant (single-antigen) vaccines are conjugated with aluminum.

One adjuvanted recombinant formulation contains the immune-stimulating adjuvant cytidine-phosphate-guanosine oligodeoxynucleotide (CpG-ODN).

Combined vaccine formulations (HepA/HepB, DTaP/HepB/IPV, and DTaP/HepB/Hib/IPV) are also available.

HepB vaccine is a routine childhood vaccination and is usually administered either individually (in neonates) or in a combination vaccine of DTaP/HepB/Hib/IPV (other ages) (1).

HepB vaccine is also indicated for all adults aged 19 through 59 years who have not been previously vaccinated (2).

HepB vaccine is also indicated for adults aged 60 years and older who have not been previously vaccinated and who have any of the following risk factors:

• A sexually active lifestyle in people who are not in a long-term, mutually monogamous relationship (eg, > 1 sex partner during the previous 6 months)

• Need for evaluation or treatment of a sexually transmitted infection

• Current or recent injection illicit drug use

• Men who have sex with men

• Employment in which workers may be exposed to blood or other potentially infectious body fluids (eg, health care, custodial, or public safety workers)

• End-stage kidney disease (eg, being treated with hemodialysis)

• HIV infection

• A chronic liver disease (eg, people with hepatitis C, cirrhosis, fatty liver disease, alcohol-related liver disease, autoimmune hepatitis, or alanine aminotransferase [ALT] or aspartate aminotransferase [AST] level greater than twice the upper limit of normal)

• Household contact and/or sexual contact with people who are positive for hepatitis B surface antigen (HBsAg)

• Travel to endemic areas

• Time spent (as patients, residents, or employees) in correctional facilities or in facilities that provide sexually transmitted infection treatment, HIV testing and treatment, drug abuse treatment and prevention services, services to injection drug users or men who have sex with men, or care for patients with developmental disabilities or with end-stage kidney disease (including those receiving long-term hemodialysis)

Adults age 60 years or older without known risk factors for hepatitis B virus infection may receive a HepB vaccine series. Any adult age 60 years or older who requests HepB vaccination should receive a HepB vaccine series.

For people 60 years of age and older with diabetes, the decision to receive the HepB vaccine should be based on shared clinical decision making (3).

The combination HepA vaccine/HepB vaccine can be used in people ≥ 18 years who have indications for either HepA or HepB vaccine and who have not been previously vaccinated with one of the vaccine components.

The main contraindications for HepB vaccine are the following:

• A severe allergic reaction (eg, anaphylaxis) after a previous dose

• Hypersensitivity to baker's yeast or any vaccine component

The main precaution with HepB vaccine is:

• Moderate or severe illness with or without a fever (vaccination is postponed until the illness resolves)

The dose for the individual recombinant HepB vaccines is 0.5 mL IM up to age 20 years or 1 mL IM for adults (≥ 20 years). The dose for the adjuvanted recombinant formulation is 0.5 mL IM for adults ≥ 18 years.

In infants, the HepB vaccine is administered in a 3-dose series once shortly after birth, at 2 months, and between 6 months and 18 months. The first dose contains only HepB; however, at 2 months and again between 6 and 18 months, a combination vaccine of DTaP/HepB/Hib/IPV is preferred in the United States.

Infants who did not receive a dose a birth should begin the series as soon as feasible. Preterm infants can still generate a protective response to most vaccines and should follow the same vaccination schedule as full-term infants. However, preterm infants who weigh < 2 kg at birth tend to have a reduced antibody response. For these infants, the first dose of the HepB vaccine should be postponed until they are discharged from the hospital or reach 1 month of age. If the first dose is administered when they are < 1 month of age, they need 3 additional doses. For preventing suspected perinatal transmission of hepatitis B in infants with positive or unknown maternal HBsAg status, see Prevention of Neonatal HBV Infection (1).

All children not previously vaccinated with HepB vaccine should be vaccinated between 11 years and 15 years of age (2). A 3-dose schedule is used; the first and second doses are separated by ≥ 4 weeks, and the third dose is administered 4 to 6 months after the second dose. However, a 2-dose schedule using Recombivax HB can be used; the second dose is administered 4 to 6 months after the first.

Adults age 19 through 59 years who have not been previously vaccinated should complete a 2- or 3-, or 4-dose series. The usual schedule for adults using recombinant vaccines is a 3-dose series with 2 doses separated by ≥ 4 weeks, and a third dose 4 to 6 months after the second dose. The recombinant adjuvanted formulation is administered in 2 doses at least 4 weeks apart.

HepB-CpG should not be administered during pregnancy because safety data are not available for use during pregnancy.

Unvaccinated adults who are being treated with hemodialysis require higher doses of the recombinant nonadjuvanted vaccines (3).

If people are not vaccinated or not completely vaccinated, the missing doses should be administered to complete the 3-dose HepB series. Adults age 60 years or older without known risk factors and who are requesting vaccination may also receive the 3-dose HepB series. The second dose is administered 1 month after the first dose; the third dose is administered ≥ 2 months after the second dose (and ≥ 4 months after the first dose). If the combined HepA/HepB vaccine is used, 3 doses are administered at 0, 1, and 6 months, or 4 doses are administered on days 0, 7, and 21 to 30, followed by a booster dose at 12 months. If a person was lost to follow-up before the series was completed, the series does not need to be restarted.

Serious adverse effects are rare and include anaphylaxis.

Mild effects include pain, redness, and swelling at the injection site. Occasionally, an increase in temperature to about 38° C, fatigue, headache, and malaise may occur but are typically mild and transient.

For more information about adverse effects of these vaccines, refer to the prescribing information.

The following English-language resources may be useful. Please note that The Manual is not responsible for the content of these resources.

1. Advisory Committee on Immunization Practices (ACIP): ACIP Recommendations: Hepatitis B Vaccine

2. ACIP: Changes in the 2025 Adult Immunization Schedule

3. Centers for Disease Control and Prevention (CDC): Clinical Information on Hepatitis B

4. European Centre for Disease Prevention and Control (ECDC): Hepatitis B: Recommended vaccinations