How is Hepatitis B (HBV) immunity achieved?

Hepatitis B Immunity: Mechanisms and Achievement

Hepatitis B immunity is achieved through two primary mechanisms: active immunity via vaccination with hepatitis B surface antigen (HBsAg), which induces protective antibodies (anti-HBs ≥10 mIU/mL) in >90% of healthy adults and ~95% of infants, or passive immunity through hepatitis B immune globulin (HBIG), which provides temporary protection for 3-6 months. 1

Active Immunity Through Vaccination

Vaccine-Induced Protection

The hepatitis B vaccine works by inducing both humoral and cellular immune responses:

• Antibody Response: The presence of anti-HBs ≥10 mIU/mL measured 1-2 months after completing the vaccine series indicates seroprotection and defines a vaccine responder 1
• Mechanism: Recombinant HBsAg vaccines (Engerix-B, Recombivax HB) contain 10-40 μg of HBsAg protein/mL with aluminum salt adjuvants to enhance immune response 1
• T-Cell Response: Vaccination induces HBs-specific T cells that produce interferon-gamma, with approximately 33% of vaccinated individuals maintaining detectable HBs-specific T cells decades after vaccination 2

Efficacy and Response Rates

The 3-dose vaccine series achieves protective antibody levels in approximately 95% of healthy infants and >90% of healthy adults aged <40 years 1:

• After the first dose: 25% of infants and 30-55% of adults achieve protective levels 1
• After the second dose: 63% of infants and 75% of adults achieve protective levels 1
• After the third dose: >90-95% achieve seroprotection 1

Factors that decrease vaccine response include: smoking, obesity, older age (especially >40 years), chronic medical conditions, diabetes, male sex, immunosuppression, and low birth weight (<2000 grams in infants) 1

Duration of Protection

Long-Term Immunity

Protection persists for 30 years or more in immunocompetent persons who initially responded to vaccination, even when anti-HBs levels fall below 10 mIU/mL 1:

• Anti-HBs levels wane over time, with only 16% of persons vaccinated at age <1 year maintaining levels ≥10 mIU/mL at 18 years, compared to 74% for those vaccinated at age ≥1 year 1
• Despite waning antibody levels, 88% of vaccinees develop an anamnestic response (≥10 mIU/mL) when given a challenge dose 30 years after initial vaccination 1
• This indicates persistent immunologic memory even without detectable circulating antibodies 1

Evidence of Non-Sterilizing Immunity

Vaccination provides clinical protection but not complete sterilizing immunity:

• Health care workers with occupational HBV exposure after vaccination developed HBcore- and polymerase-specific CD4+ and CD8+ T cells, despite never developing anti-HBcore antibodies (the standard marker of infection) 2
• These T cells were predominantly CD45RO+CCR7-CD127- effector memory cells, similar to those in patients with natural immunity 2
• This demonstrates that vaccinated individuals can experience subclinical viral exposure that is rapidly controlled without developing detectable infection 2

Passive Immunity Through HBIG

Mechanism and Duration

HBIG provides immediate but temporary protection:

• Duration: Provides passively acquired anti-HBs for 3-6 months 1
• Detection: Passively acquired anti-HBs can be detected for 4-6 months after HBIG administration 1
• Primary use: For individuals who do not respond to vaccination, HBIG alone is the primary means of protection after HBV exposure 1

Clinical Applications

HBIG is most effective when combined with active vaccination 3:

• Perinatal exposure: One dose of HBIG at birth plus vaccine series is 85-95% effective in preventing chronic HBV carrier state in infants born to HBsAg-positive, HBeAg-positive mothers 3
• Acute exposure: Two doses of HBIG (one after exposure, one month later) is approximately 75% effective in preventing hepatitis B after needlestick injury 3
• Sexual exposure: Single dose of HBIG is 75% effective if given within 2 weeks of last sexual exposure to person with acute hepatitis B 3

Natural Immunity

Recovery from Infection

Approximately 95% of adults with normal immune status who acquire HBV infection develop self-limited disease with lasting immunity 1:

• The immune system eliminates virus from blood through both humoral (anti-HBs antibodies) and cellular (cytotoxic T-lymphocytes) mechanisms 4
• Natural infection induces broader immune responses than vaccination, including antibodies to HBcore and T cells specific for multiple viral antigens 4, 2
• Chronic infection occurs in <5% of infected adults, ~30% of children aged <5 years, and ~90% of infected infants 1

Key Clinical Considerations

Important caveats for clinical practice:

• Each vaccine dose confers some protection; concerns about series completion should not delay vaccination initiation 1
• Vaccine immunogenicity is not decreased by lengthened intervals between doses 1
• Booster doses are generally not recommended for immunocompetent individuals who initially responded to vaccination, as immunologic memory persists despite waning antibody levels 1
• Post-vaccination serologic testing is only recommended for specific high-risk groups (healthcare workers, immunocompromised patients, infants born to HBsAg-positive mothers) 1