What is the difference between recombinant (recombinant DNA technology) hepatitis B vaccine shots?

Hepatitis B Recombinant Vaccines: Understanding the Differences

All currently available hepatitis B vaccines in the United States are recombinant DNA vaccines—there is no longer a plasma-derived vaccine on the market—so when asking about "recombinant" vaccines, you're actually asking about the differences between the specific recombinant vaccine formulations available. 1

What "Recombinant" Means

All modern hepatitis B vaccines use recombinant DNA technology where the hepatitis B surface antigen (HBsAg) gene is inserted into Saccharomyces cerevisiae (baker's yeast), which then produces the HBsAg protein 1, 2. This replaced the older plasma-derived vaccines that are no longer manufactured in the United States 1.

Key Differences Between Available Recombinant Vaccines

Single-Antigen Vaccines

Recombivax HB (Merck):

• Contains 5-40 μg of recombinant HBsAg depending on age and indication 1
• Standard 3-dose schedule at 0,1, and 6 months for most patients 1
• Special 2-dose option: Adolescents aged 11-15 years can receive 10 μg doses at 0 and 4-6 months (adult formulation) 1
• Approved for all ages from birth onward 1, 3

Engerix-B (GlaxoSmithKline):

• Contains 10-40 μg of recombinant HBsAg depending on age 1, 2
• Standard 3-dose schedule at 0,1, and 6 months 1
• Approved for all ages from birth onward 1, 3
• Achieves 70.5%-90.2% protective antibody response in adults 1

Heplisav-B (Dynavax):

• Contains 20 μg of recombinant HBsAg with a novel CpG 1018 adjuvant 1, 3
• Only 2-dose schedule: Given at 0 and 1 month 1, 3
• Superior immunogenicity: Achieves approximately 90% protective response compared to 70.5%-90.2% with Engerix-B 1
• Major restriction: Only approved for adults ≥18 years; cannot be used in infants, children, adolescents, pregnant women, or hemodialysis patients 1, 3

Combination Vaccine

Twinrix (GlaxoSmithKline):

• Contains 20 μg recombinant HBsAg plus inactivated hepatitis A virus 1, 3
• Standard 3-dose schedule at 0,1, and 6 months 1, 4
• Only for adults ≥18 years who need protection against both hepatitis A and B 1, 3
• Should not be used solely for hepatitis B protection 3

Practical Clinical Differences

Dosing Schedules:

• Most vaccines require 3 doses over 6 months 1
• Heplisav-B offers faster completion with only 2 doses over 1 month 1, 3
• Recombivax HB offers a 2-dose option specifically for adolescents 11-15 years 1

Immunogenicity:

• After first dose: 30%-55% achieve protective levels 1
• After second dose: 75% achieve protective levels 1
• After third dose: >90% achieve protective levels with standard vaccines 1
• Heplisav-B achieves ~90% protection with just 2 doses 1

Age-Related Response:

• Response declines after age 40 years, dropping below 90% 1
• By age 60, only 75% achieve protective antibody levels with standard 3-dose regimens 1
• Heplisav-B's novel adjuvant may overcome some age-related decline 1, 3

Special Populations:

Hemodialysis patients:

• Require 40 μg doses (double the standard adult dose) 1
• Recombivax HB: 40 μg given as 1.0 mL at 0,1, and 6 months 1
• Engerix-B: 40 μg given as two 1.0 mL doses at one site on a 4-dose schedule at 0,1,2, and 6 months 1
• Heplisav-B can be used at standard 20 μg dose but is not extensively studied in this population 1, 3

Immunocompromised patients:

• Higher doses may be more immunogenic 1
• Standard adult doses often inadequate 3

Common Pitfalls to Avoid

• Do not use Heplisav-B in children, adolescents, or pregnant women—it is only approved for adults ≥18 years 1, 3
• Do not use standard adult doses in hemodialysis patients—they require the 40 μg dialysis formulation 1, 3
• Do not administer in the buttock—immunogenicity is substantially lower; use deltoid in adults/children or anterolateral thigh in infants 1
• Do not use Twinrix solely for hepatitis B—reserve it for patients needing both hepatitis A and B protection 3

Storage and Safety

• All vaccines must be stored at 2°C to 8°C and should never be frozen 5
• All current U.S. formulations are thimerosal-free or contain only trace amounts (<1.0 μg mercury/mL) 1, 3
• Vaccines are generally well tolerated with pain at injection site (20%-41%) and headache (9%-13%) being most common 1, 6
• Anaphylaxis occurs in approximately 1 per 1.1 million doses 1