Hep B vaccination
Monovalent HB Vaccines
- Engerix-B (GlaxoSmithKline)
- H-B-Vax II (Merck Sharp & Dohme)
Combination Vaccines for Pediatric Use
- DTPa-HB-IPV-Hib—Hexaxim (Sanofi-Aventis): Combines protection against diphtheria, tetanus, pertussis (acellular), hepatitis B, poliovirus, and Haemophilus influenzae type b.
- DTPa-HB-IPV/Hib—Infanrix hexa (GlaxoSmithKline): Similar combination, providing broad coverage for common pediatric diseases.
Combination Vaccines with Hepatitis A
- Twinrix (GlaxoSmithKline):
- Standard Twinrix: 1 mL dose containing 720 ELISA units of HA and 20 μg of HBsAg.
- Twinrix Junior: 0.5 mL dose containing 360 ELISA units of HA and 10 μg of HBsAg.
- Offers combined protection against hepatitis A and B.
Interchangeability and Safety
- Interchangeability: HB vaccines from different manufacturers can be used interchangeably during a vaccination course.
- Thiomersal-Free: All HB-containing vaccines available in Australia do not contain thiomersal, making them suitable for individuals concerned about this preservative.
Seroconversion and Immune Response
- Achievement of Seroconversion:
- Post three-dose HB vaccine course, seroprotective antibody levels are achieved in over 95% of healthy infants, children, and adolescents.
- Over 90% of adults under 40 years achieve seroprotection, with rates decreasing with age.
- By age 60, seroprotection rates can drop to 65–75%.
- Post-Dose Response Rates:
- 30–55% of healthy adults under 40 achieve seroprotection after the first dose.
- 75% achieve seroprotection after the second dose.
- Rapid schedule recommendations:
- The (0, 1, 2 months) and accelerated (0, 7, 21 days) schedules for Engerix-B should be followed by a fourth dose at 12 months.
- Similar recommendations apply to Twinrix following the 0, 7, 21 days schedule.
- Effect of Fourth Dose:
- Increases seroprotection rate to near 100% and significantly boosts antiHBs titre.
- Interval Between Doses:
- A longer interval between the second and third doses tends to produce a higher antibody level but delays optimal protection.
Decline of Antibodies
- Rate of Decline: Antibody titres decline rapidly in the first year and more gradually thereafter.
- Long-Term Persistence:
- 15–50% of infants and children lose detectable antibodies within 5–15 years.
- In adults, 7–50% show antibody levels below 10 mIU/mL after 5 years, increasing to 30–60% within 9–11 years.
- After 30 years, approximately two-thirds of vaccinated individuals have antiHBs levels below 10 mIU/mL.
- Vaccine Efficacy in Older Adults
- Comparison Study: In a German study involving individuals over 60, Twinrix showed a higher seroprotection rate (88.2%) compared to Engerix-B (73%) and Merck’s HB vaccine (56.3%).
- Trend Across All Ages: Similar trends in seroprotection favoring Twinrix were observed across various age groups.
- Booster Doses
- Current Recommendations: Major health authorities like ATAGI, WHO, CDC, and the Viral Hepatitis Prevention Board do not recommend routine booster doses for immunocompetent individuals, regardless of age or occupation.
- Need for Boosters: Determination of the need for booster doses relies on long-term follow-up studies
Long-Term Efficacy and Breakthrough Infections
- Chronic Infection Protection:
- Subclinical infections may become more common over time, but protection against clinical disease and chronic infection persists.
- Anamnestic Response:
- Most individuals who lose detectable antibody still exhibit a brisk anamnestic response to a booster dose, indicating sustained immunological memory.
- Breakthrough Infections:
- Rare in immunocompetent individuals and typically occur only among infants born to infected mothers.
- Immunocompromised individuals remain protected as long as antiHBs levels are ≥10 mIU/mL.
Efficacy of HB Vaccine
- Protection Levels:
- Virtually complete protection against disease and both acute and chronic infection for those with antiHBs ≥10 mIU/mL.
- Lesser protection for those who seroconvert but do not reach the seroprotective level of ≥10 mIU/mL.
- Clinical Disease Post-Vaccination:
- Clinical disease has not been observed in follow-up studies of immunocompetent vaccine responders, despite the decline in antibody levels.
Adverse Events
- Common Reactions:
- Systemic symptoms like nausea, malaise, and dizziness are uncommon.
- Low-grade fever occurs in 2–3% of cases.
- Soreness at the injection site is reported in 3–29% of individuals and usually lasts less than 24 hours.
- Rare Reactions:
- Anaphylaxis and transient alopecia are rare, but adrenaline should be available for immediate use.
- Serious Adverse Events:
- Conditions such as Guillain-Barré syndrome, multiple sclerosis, diabetes mellitus, rheumatoid arthritis, and other autoimmune diseases are not associated with the HB vaccine.
Contraindications and Precautions
- General Safety: Safe and indicated from birth and for all immunocompromised individuals.
- Specific Contraindications:
- Previous anaphylactic reaction to a HB vaccine dose or any vaccine component.
- Anaphylactic allergy to baker’s yeast is a theoretical contraindication, though evidence of issues related to yeast allergy is not convincing.
- Use alternative products for individuals with latex allergy due to the presence of latex in H-B-Vax II.
- Pregnancy and Lactation:
- Neither is a contraindication to HB immunization, though vaccination during the second and third trimesters is preferred over the first.
Interactions
- Co-administration with Other Vaccines:
- HB vaccine can be administered concurrently with any other immunizing agent.
- Co-administration with HBIG is indicated for infants born to HB-infected mothers or for exposures in susceptible individuals.
- Co-administration with HA (in Twinrix) may enhance the immunogenicity of the HB component.
Testing for Immunity After Immunisation
Post-immunisation antibody testing is best done 1–3 months after the third dose in those at high or occupational risk, at increased risk of severe disease or who are less likely to respond well to vaccine.
- ATAGI Recommendations:
- Testing is recommended 4–8 weeks after completing the vaccination course in individuals at occupational risk, those at risk of severe disease, or expected poor responders.
- Additional Considerations:
- Some studies suggest testing 3 months post-vaccination.
- Suggested to perform testing 1–3 months after the last dose, but up to 6 to 12 months later is acceptable.
- Testing should include HBsAg, antiHBc, and antiHBs to check for chronic infection, previous exposure, and response to immunization.
Management of Non-responders to HB Vaccine
Definition of a Non-Responder:
- Not infected with hepatitis B virus.
- Documented history of age-appropriate hepatitis B vaccination.
- Anti-HBs levels <10 mIU/mL, measured 4-8 weeks post-booster dose.
Recommendations for Further Management:
- Offer additional doses if chronic hepatitis B infection has been excluded.
- Administer a single booster dose (4th dose) to confirm non-responder status.
- If still non-responsive, test for hepatitis B virus infection.
- If negative, administer 2 more doses of the hepatitis B vaccine, spaced 1 month apart.
- Consider the 4th booster dose as the 1st of these 3 repeat doses.
- Re-test for anti-HBs levels at least 4 weeks after the final dose.
Alternative Strategies:
- High-Dose or Double-Dose Regimens:
- Some evidence suggests that higher-dose or double-dose formulations may work for some non-responders.
- However, evidence is inconsistent on their effectiveness for broader application.
- Intradermal Vaccination:
- Some studies report success with intradermal vaccination in non-responders to multiple intramuscular doses (≥5 doses total).
- Up to 4 doses of Engerix-B (0.25 mL [5 μg] per dose) have been used.
- Younger age and longer duration (≥6 months) since the last intramuscular dose may increase response likelihood.
- Anti-HBs levels should be measured before each subsequent intradermal dose.
Persistent Non-Responders:
- See the relevant public health guidelines for post-exposure prophylaxis details.
- These individuals are likely not protected against hepatitis B.
- Minimize potential exposure to hepatitis B.
- Advise the need for hepatitis B immunoglobulin within 72 hours of parenteral or mucosal exposure to hepatitis B virus.
Options for Travelers
- Accessing Novel Vaccines: Travelers who do not respond to available vaccines in Australia might consider accessing novel HB vaccines available in other countries, which may offer different formulations potentially more effective for them.