A randomized trial of alternative two- and three-dose hepatitis B vaccination regimens in adolescents: Antibody responses, safety, and immunologic memory

Objectives. Hoping to increase hepatitis B (HB) vaccination of adolescents, we did the following: 1) studied if modified regimens of the recombinant H B vaccine, Recombivax HB (2 or 3 doses of 5 or 10 mug given over 4 or 6 mon ths), induce protective anti-hepatitis B surface antibody [anti-HBsAb] leve ls (greater than or equal to 10 mIU/mL) comparable to the recommended regim en (5 mug at 0 and 1, and 6 months); 2) measured early antibody response af ter a single dose; and 3) assessed immunologic memory after 2- and 3-dose r egimens. Design. One thousand twenty-six adolescents were randomized to 1 of 5 treat ment groups (10 mug at 0 and 4 or 0 and 6 months; 5 mug 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 severa l other times in a subset of vaccinees. Anti-HBsAb response to a booster do se 2 years later was examined to assess immunologic memory in participants vaccinated with 5 mug at 0 and 6 or 0, 1, and 6 months. Results. All regimens induced (greater than or equal to 10 mIU/mL of anti-H Bs in greater than or equal to 95% of vaccinees. Geometric mean titers rang ed from 674.8 to 3049.4 mIU/mL. Geometric mean titers were higher with regi mens using the following: 1) 10 versus 5 mug; 2) 3 versus 2 doses; and 3) v accination intervals of 6 versus 4 months. After 6 months, 63.8% of vaccine es given one 10-mug dose had greater than or equal to 10 mIU/mL of anti-HBs Ab versus 41.6% after one 5-mug dose. Participants vaccinated with either t wo or three 5-mug doses retained robust immunologic memory. Conclusions. The results of this study show that a 2- dose regimen of Recom bivax HB is as immunogenic and induces immunologic memory as effectively as the recommended 3-dose regimen. A regimen of two 10-mug doses may be of si gnificant benefit for vaccinees who are poorly compliant or deviate from th e intended vaccination schedule.