VaxTeen Hepatitis B Vaccine Booster Study
Condition: Hepatitis
MeSH terms: Hepatitis A; Hepatitis B; Hepatitis
Study type: Interventional
Phase: Phase 4

Summary: 
      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.
    

Detailed description: 
      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.
    

Intervention name(s): hepatitis B vaccine
Intervention type(s): Biological
Allocation: Non-Randomized
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Prevention
Keywords: vaccine; hepatitis B; immune memory