OBJECTIVESTo evaluate the long-term efficacy of revaccination in non-responder children to primary hepatitis B (HB) vaccination and to compare the efficacy of low-dose intradermal inoculation to that of routine-dose intramuscular inoculation.

METHODS40 healthy non-responder children to primary HB vaccination identified by screening were given a three-dose revaccination randomly by intramuscular (n = 17, 10 microg per dose) or intradermal route (n = 23, 2 microg per dose) since September, 1999, and their blood specimens were collected regularly for testing for HB virus markers up to five years. Another 80 responder children to primary HB vaccination were also followed-up as controls without revaccination. By the end of five-year follow-up, HBsAg-specific lymphocyte response was investigated in vitro, and a booster dose (5 microg) was given to those with negative conversion of anti-HBs and their anamnestic responses were evaluated 12-14 days later.

RESULTSSerum anti-HBs did not reach 10 IU/L only in one of 40 non-responder children, who received intradermal revaccination. In the fifth year after revaccination, 50% of the non-responder children who received intramuscular revaccination still maintained anti-HBs of > or = 10 IU/L, though the rate was significantly lower than 85% in controls. Following the booster dose, a robust anamnestic response was developed in all of 8 intramuscular revaccinees and 11 controls but 16 of 18 intradermal revaccinees, who lost anti-HBs of > or = 10 IU/L over time, and geometric mean titers of anti-HBs climbed to 208, 105, and 549 IU/L, respectively. Secretions of HBsAg-specific interleukin-2 and -5 could be detected in peripheral blood mononuclear cell samples of more than 70% of non-responder children. Person-year infection rates of HB virus were 8.9% (8/89.9 person-years) for intradermal revaccinees, significantly higher than 3.6% (12/337.2 person-years) in controls, and 4.3% (3/70.2 person-years) for intramuscular revaccinees, approximating to that of controls, based on positive conversion of anti-HBc.

CONCLUSIONSThree-dose intramuscular revaccination did play an important immune protection for non-responder children to primary HB vaccination, but its efficacy could not reach the level of primary vaccination in responders. Low-dose intradermal inoculation was not as effective as route-dose intramuscular inoculation with the same doses in revaccination for non-responder children to primary HB vaccination.