Persistence of Antibody and Response to Booster of a Recombinant Hepatitis B Vaccine in Children Who Responded to a Primary Course of 2.5µg Recombinant Hepatitis B Vaccine as Infants

In the 1970s, Alaska Natives had the highest rate of hepatitis B virus (HBV) infection in the US. Because of this, routine vaccination for all Alaska Native infants beginning at birth was implemented in 1985. Hepatitis B vaccination programs have resulted in significant declines in acute and chronic HBV infections among Alaska Natives, with virtually no new chronic infections observed among the vaccinated cohort. Since 1991, the American Academy of Pediatrics (AAP) and the Advisory Committee on Immunization Practices (ACIP) have recommended hepatitis B vaccination for all infants, preferably beginning at birth. Beginning vaccination during infancy prevents childhood acquisition of HBV, and provides immunity against HBV before individuals reach an age where they may be at increased risk of exposure due to high-risk behaviors (i.e., sexual activity and drug use) or occupation.

The success of this vaccination strategy is contingent on the vaccine being able to induce long-lasting protection. The duration of protection conferred by hepatitis B vaccination initiated at birth is not firmly established. Over 95% of vaccinees in clinical studies develop a response to the three-dose primary hepatitis B vaccination series, defined as the development of antibody to hepatitis B virus surface antigen (anti-HBs) to concentrations greater than10 milliInternational Units per milliliter (mIU/mL) in blood. Within 5-10 years after the primary series, anti-HBs concentrations decline and for many vaccinees, concentrations will fall below 10mIU/mL, or even below detectable levels.

However, despite low anti-HBs concentrations, HBV infections (as measured by the presence of markers of infection such as hepatitis B surface antigen [HBsAg] or antibody to hepatitis B core antigen [anti-HBc]) are rare in persons who have been shown to respond to the primary vaccine series. Continued protection against HBV infection in these children is likely provided by immune memory cells generated at the time of the primary series. An immunologic memory response (also termed an anamnestic response) can be evaluated by measuring the effect of an additional (booster) dose of hepatitis B vaccine. An anamnestic response is generally defined as a rapid (within 14-30 days) two-fold or greater increase in the anti-HBs titer to at least 20mIU/mL. This signifies that immune memory cells capable of generating a rapid rise in anti-HBs are still functional and would protect against HBV infection. Blood tests that can identify memory B cells that are specific for vaccine antigens are now available, and could be used to provide additional evidence of immune memory.9

Although there is good evidence that the immunologic memory for HBsAg exceeds the persistence of measurable antibodies, few studies have examined lasting protection (>10 years) against HBV infection in a low-risk population vaccinated at birth with recombinant vaccine.10 Most studies demonstrating long term protection from infection and persistent immune memory despite low anti-HBs concentrations have been performed among children living in areas where HBV infection is endemic, or whose mothers had chronic HBV infection (i.e., children at high risk of perinatal or childhood HBV infection). Studies conducted among Alaska Native children have demonstrated that "low-risk" children (i.e., infants who were born to HBsAg-negative mothers with no HBsAg-positive persons living in their households) also have concentrations of anti-HBs that fall below 10mIU/mL during later childhood. In a cohort of 36 children known to have responded to a recombinant vaccine series starting at birth, none retained levels of anti-HBs ≥ 10mIU/mL at 7.5 years of age. In addition, three of these children failed to exhibit an anamnestic response to a booster dose given at an average age of 7.5 years.

At the present time, neither measurement of anti-HBs concentrations nor booster dose(s) are recommended for low-risk children after the hepatitis B vaccine primary series given during infancy. Low-risk Alaska Native children who received recombinant hepatitis B vaccination starting at birth are now reaching adolescence, a period when the risk of HBV infection through sexual transmission or transmission by injecting drug use is more likely to occur. More information is needed to determine if protection against HBV infection among children entering adolescence is adequate or if booster dose(s) might be necessary.