What to do if there's no immune response to 3 doses of Engerix B (hepatitis B vaccine)?

Management of Hepatitis B Vaccine Non-Response After 3 Doses of Engerix-B

For adults who fail to respond to 3 doses of Engerix-B, the preferred approach is revaccination with Heplisav-B (2-dose series at 0 and 1 month), which achieves approximately 90% seroprotection compared to 70.5-90.2% with traditional vaccines, or alternatively use a high-dose Engerix-B regimen (40 μg at 0,1,2, and 6 months). 1

Initial Assessment

Before proceeding with revaccination, confirm true non-response by:

• Testing anti-HBs levels 1-2 months after the third dose to document non-response (anti-HBs <10 mIU/mL). 2, 1
• Ensuring the original vaccination series was completed with appropriate intervals (minimum 4 weeks between doses 1-2,8 weeks between doses 2-3, and 16 weeks between doses 1-3). 3

Revaccination Strategy

First-Line Approach: Heplisav-B

• Administer Heplisav-B as a 2-dose series (20 μg per 0.5 mL dose) at 0 and 1 month. 1
• This vaccine contains an immunostimulatory adjuvant that produces faster and higher response rates than traditional vaccines. 4
• Heplisav-B achieves protective antibody levels in 79% of recipients after just one dose and 100% by one week after the second dose, compared to only 12% and 18% respectively with Engerix-B. 4

Alternative Approach: High-Dose Engerix-B

If Heplisav-B is unavailable:

• Administer 40 μg of Engerix-B (2 × 20 μg) on a 4-dose schedule at 0,1,2, and 6 months. 1, 5
• This high-dose regimen is particularly important for older adults due to age-related immune senescence. 1
• In hemodialysis patients (who have similar immune challenges), this regimen achieved 67% seroprotection with a geometric mean titer of 93 mIU/mL. 5

Second-Line Alternative: Adjuvanted Vaccine

• Consider Fendrix (if available), which contains AS04 adjuvant and demonstrates significantly better response rates than standard Engerix-B revaccination in previous non-responders. 6
• A single dose of Fendrix or high-dose HBVaxPro-40 performs significantly better than three doses of standard Engerix-B in revaccination. 6

Post-Revaccination Testing

• Test anti-HBs levels 1-2 months after completing the revaccination series to confirm seroprotection (≥10 mIU/mL). 2, 1
• If HBIG was administered for post-exposure prophylaxis, delay testing until 4-6 months after HBIG administration when passive antibodies are no longer detectable. 2

Management of Persistent Non-Response

After First Revaccination Series

• If non-response persists after the first revaccination series, administer a second complete 3-dose vaccine series. 2
• For occupational exposures in documented non-responders to one 3-dose series: give 1 dose of HBIG plus restart a second 3-dose vaccine series if the source is HBsAg-positive. 2

After Second Revaccination Series (Total of 6 Doses)

• Individuals who remain non-responsive after two complete 3-dose series (6 total doses) are considered true non-responders and should not receive additional vaccination. 2
• For occupational exposures in these true non-responders: administer 2 doses of HBIG one month apart if the source is HBsAg-positive or high-risk. 2
• These individuals require counseling about their susceptibility and the need for HBIG prophylaxis after any future hepatitis B exposures. 2

Important Clinical Considerations

Age-Related Factors

• Response rates decline with age, with >90% seroconversion in adults under 40 years but lower rates in older adults. 3
• The high-dose regimen becomes increasingly important for patients over 40 years old. 1

Vaccine Interchangeability

• Different hepatitis B vaccines can be used interchangeably to complete a series, as they produce immunologically comparable antibodies. 5
• Completing a course with one dose of Engerix-B after two doses of Recombivax HB produces similar antibody titers to three doses of Recombivax HB alone. 5

Common Pitfalls to Avoid

• Do not restart the vaccination series if interrupted—simply continue where you left off. 1, 3
• Do not assume that initial non-responders are true non-responders without attempting at least one revaccination series, as many are actually hyporesponders who will respond to additional doses. 7
• Do not use standard 20 μg doses for revaccination when high-dose (40 μg) regimens are indicated, as this significantly reduces response rates. 1, 5
• Do not delay post-vaccination testing beyond 2 months, as antibody levels may decline and you need to document peak response. 2, 1

Long-Term Protection

• Individuals who develop protective antibody levels following vaccination are considered protected even if antibody levels subsequently decline below 10 mIU/mL, as immune memory persists. 1
• Vaccine-induced immunity can persist for more than 30 years in responders. 3
• However, in dialysis patients and immunocompromised individuals, antibody levels should be monitored regularly as protection may wane. 8