A Randomized Trial of Alternative Two- and Three-Dose Hepatitis B Vaccination Regimens in Adolescents: Antibody Responses, Safety, and Immunologic Memory

Abstract

Objectives. Hoping to increase hepatitis B (HB) vaccination of adolescents, we did the following: 1) studied if modified regimens of the recombinant HB vaccine, Recombivax HB (2 or 3 doses of 5 or 10 μg given over 4 or 6 months), induce protective anti-hepatitis B surface antibody [anti-HBsAb] levels (≥10 mIU/mL) comparable to the recommended regimen (5 μg at 0 and 1, and 6 months); 2) measured early antibody response after a single dose; and 3) assessed immunologic memory after 2- and 3-dose regimens. Design. One thousand twenty-six adolescents were randomized to 1 of 5 treatment groups (10 μg at 0 and 4 or 0 and 6 months; 5 μg at 0 and 6 or 0, 2, and 4 or 0, 1, and 6 months) in an open trial. Anti-HBsAb was measured in all participants just before and 1 month after the last dose, and at several other times in a subset of vaccinees. Anti-HBsAb response to a booster dose 2 years later was examined to assess immunologic memory in participants vaccinated with 5 μg at 0 and 6 or 0, 1, and 6 months. Results. All regimens induced ≥10 mIU/mL of anti-HBs in ≥95% of vaccinees. Geometric mean titers ranged from 674.8 to 3049.4 mIU/mL. Geometric mean titers were higher with regimens using the following: 1) 10 versus 5 μg; 2) 3 versus 2 doses; and 3) vaccination intervals of 6 versus 4 months. After 6 months, 63.8% of vaccinees given one 10-μg dose had ≥10 mIU/mL of anti-HBsAb versus 41.6% after one 5-μg dose. Participants vaccinated with either two or three 5-μg doses retained robust immunologic memory. Conclusions. The results of this study show that a 2-dose regimen of Recombivax HB is as immunogenic and induces immunologic memory as effectively as the recommended 3-dose regimen. A regimen of two 10-μg doses may be of significant benefit for vaccinees who are poorly compliant or deviate from the intended vaccination schedule.