Differences in Response to a Hepatitis B Vaccine Booster among Children and Adolescents Vaccinated during Infancy

Children in the U.S. receive a series of hepatitis B virus (HBV) vaccinations as part of their routine childhood immunizations. Since routine vaccination was implemented in the early 1980s, rates of chronic hepatitis B have fallen significantly in the vaccinated age groups.

There are scant data regarding the duration of protection provided by hepatitis B vaccination. However, the presence of immune memory can be evaluated indirectly by measuring the immune response (or anamnestic response) to a booster dose of the vaccine.

In a study published in the July 16, 2007 online edition of Pediatrics, researchers enrolled 378 healthy participants recruited at the Alaska Native Medical Center between October 2001 and January 2004, including:

• 74 adolescents (aged 12-15 years) who had received a plasma-derived 3-dose primary vaccine series;

• 138 adolescents (aged 10-15 years) who had received a recombinant 3-dose primary vaccine series;

• 166 children (aged 5-7 years) who had received a recombinant 3-dose primary vaccine series.

All subjects were born to hepatitis B surface antigen (HBsAg)-negative mothers and received their first dose of HBV vaccine within 7 days after birth.

The study investigators determined the proportion of participants with serologic evidence of protective immunity (antibody to HBsAg >10 mIU/mL) at baseline (pre-booster), the proportion who developed an anamnestic response (increase -to >10 mIU/mL or at least a 4-fold increase in antibody to HBsAg to >10 mIU/mL), and the geometric mean concentration by 1, 2, and 4 weeks after a 5 microgram recombinant vaccine booster dose.

Results

• No participant had evidence of chronic HBV infection.

• Overall, an anamnestic response to a booster dose of the vaccine was observed in:

- 99% of the children who received the recombinant vaccine;
- 83% of the adolescents who received the recombinant vaccine;
- 69% of the adolescents who received the plasma-derived vaccine.

• Among responders, the geometric mean concentrations at 2 weeks post-booster were 3360 and 128 mIU/mL, respectively, among adolescents who received plasma-derived vaccine with antibodies to HBsAg >10 and <10 mIU/mL at baseline.

• Concentrations were 1283 and 369 mIU/mL, respectively, among adolescents who received recombinant vaccine, and 5091 and 696 mIU/mL, respectively, among children who received recombinant vaccine.

• The anamnestic response rate at 2 weeks post-booster among participants with antibodies to HBsAg <10 mIU/mL at baseline was inversely associated with age.

• 97% of 5-year-olds responded, compared with 60% of 14-year-olds.

Conclusion

Based on these findings, the authors concluded, "Although most participants responded to a booster dose of hepatitis B vaccine, the significance of the increased proportion of non-responders among older adolescents might indicate waning immune memory."

However, they added in their discussion, "Among vaccinated persons who have lost the capacity to mount a detectable anamnestic response, protection from chronic infection or symptomatic infection might persist even if protection from acute, asymptomatic infection is no longer present."

Division of Viral Hepatitis, Epidemic Intelligence Service, Epidemiology Program Office, Centers for Disease Control and Prevention, Atlanta, GA; Liver Disease and Hepatitis Program, Alaska Native Tribal Health Consortium, Anchorage, AK.

08/28/07

Reference
T Samandari, A E Fiore, and S Negus. Differences in Response to a Hepatitis B Vaccine Booster Dose Among Alaskan Children and Adolescents Vaccinated During Infancy. Pediatrics 120(2): e373-e382. August 2007 [Published online July 16, 2007] doi:10.1542/peds.2007-0131.