VaxTeen Hepatitis B Vaccine Booster Study
VaxTeen Hepatitis B Vaccine Booster Study
The purpose of this study is to determine immune status of adolescents who responded to a
 primary series of recombinant hepatitis B vaccine given at birth and to assess their response
 to a booster dose of vaccine.
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.

 The specific objectives are as follows:

 Primary

 1. To determine anti-HBs concentrations among adolescents aged 11-14 years old who
 responded to a primary series of recombinant hepatitis B vaccine initiated at birth.

 2. To assess the anti-HBs response to a booster dose of recombinant hepatitis B vaccine
 among adolescents who have been previously shown to respond to a primary series of
 recombinant hepatitis B vaccine initiated at birth.

 3. To determine whether specific immune memory cells are present among the study cohort
 members.

 Secondary

 1. To correlate the response to a booster dose of hepatitis B vaccine with

 1. initial response to the primary series

 2. concentration of anti-HBs and age at time of a booster dose.

 2. To document side effects in persons receiving a fourth dose of hepatitis B vaccine.

 3. To determine the proportion of children who received and responded to a primary vaccine
 series in infancy who subsequently became infected with HBV as demonstrated by the
 presence of anti-HBc and/or HBsAg.
Inclusion Criteria:

 -  Eligible children are those who received the 2.5 µg/dose three-dose series of
 Recombivax HB® with the first dose having been given during the first week of life and
 the series completed by 9 months. All children were born to HBsAg

 -  negative mothers, had no HBsAg-positive persons living in their households at the time
 of immunization, and had a minimum of one serologic specimen prior to the age of 18
 months with results indicating an anti-HBs concentration of ≥10mIU/mL.

 Exclusion Criteria:

 -  Receipt of a fourth dose of any hepatitis B vaccine

 -  History of allergic reaction after receiving hepatitis B vaccine or hypersensitivity
 to any components of the hepatitis B vaccine used for the booster dose

 -  History of hepatitis B virus infection

 -  Existence of disease known to affect the immune system (e.g., HIV, AIDS, SCID, chronic
 renal disease, cancer)

 -  Current or recent (within 6 months) receipt of immunomodulatory therapy (e.g.,
 systemic corticosteroids, chemotherapy) or blood products