A randomized, controlled study in adults of the immunogenicity of a novel hepatitis B vaccine containing MF59 adjuvant p Thomas C. Heineman a , Mary Lou Clements-Mann b, 1 , Gregory A. Poland c , Robert M. Jacobson c , Allen E. Izu d , Doreen Sakamoto d , Joseph Eiden d, 2 , Gary A. Van Nest d, 2 , Henry H. Hsu d, * a Division of Infectious Diseases and Immunology, St. Louis University, 3635 Vista Avenue, P.O. Box 15250, St. Louis, MO, 63110-0250, USA b Center for Immunization Research, Johns Hopkins University School of Hygiene and Public Health, Baltimore, MD, USA c Department of Medicine, Mayo Vaccine Research Group, 611C Guggenheim Building, Mayo Clinic and Foundation, 200 First Street, SW, Rochester, MN 55905, USA d Vaccines and Therapeutics Clinical Research, Chiron Corporation, 4560 Horton Street, Emeryville, CA 94608, USA Received 11 January 1999; received in revised form 17 February 1999; accepted 18 February 1999 Abstract The safety and immunogenicity of a novel hepatitis B virus (HBV) vaccine containing recombinant PreS2 and S antigens combined with MF59 adjuvant (HBV/MF59) was evaluated in healthy adults (N=230) who were randomized to receive 2 or 3 immunizations of either the study vaccine or a licensed control vaccine (Recombivax HB 1 ). After a single immunization, 105 of 118 (89%) recipients of HBV/MF59 achieved protective serum levels of anti-HBs antibody (>10 mIU/ml), compared with 13 of 110 (12%) recipients of licensed vaccine (P < 0.001). The geometric mean titer (GMT) after 2 doses of HBV/MF59 given 2 months apart (13,422 mIU/ml) was more than 5-fold higher than that following 3 doses of licensed vaccine given over 6 months (2,346 mIU/ml; P < 0.001). The GMT following 3 injections of HBV/MF59 (249,917 mIU/ml) was 100-fold higher than licensed vaccine (P < 0.001). Anti-PreS2 antibodies were elicited in over 90% of the subset of HBV/MF59 recipients tested. Both vaccines were well tolerated; transient, mild-to-moderate local in¯ammation was the major postinjection reaction. # 1999 Elsevier Science Ltd. All rights reserved. Keywords: Hepatitis B vaccine; Adjuvant, immunologic; Clinical trials 1. Introduction Hepatitis B vaccines have been available in the United States since 1981 and have proved safe and eective in preventing HBV infection (reviewed in [1]). Nonetheless, hepatitis B remains a major public health problem worldwide. The CDC estimated that there were more than 330,000 new HBV infections per year in the US during the period from 1988±1994 [2]. The currently licensed HBV vaccines in the US in- corporate the hepatitis B surface antigen (HBsAg) pro- duced in recombinant yeast and contain aluminum salts (alum) as adjuvant [3±5]. They are administered in a 3-dose series on a 0-, 1-, and 6-months schedule in adults. Between 50 to 95% of healthy recipients develop seroprotective anti-HBs antibody titers after the second dose, depending upon age and body weight [6±8]. Because 1 or 2 doses of the current vaccines are insuciently immunogenic to reliably protect against infection, a limitation to more widespread and con- venient use of these vaccines is the need for 3 injec- Vaccine 17 (1999) 2769±2778 0264-410X/99/$ - see front matter # 1999 Elsevier Science Ltd. All rights reserved. PII: S0264-410X(99)00088-2 p Presented in Part: American Association for the Study of Liver Diseases, Washington, DC. May 10±16, 1997 (Abstract 280); 37th ICAAC, Toronto, September 28±October 1, 1997 (Abstract H-12) 1 Deceased. 2 Current address: Dynavax Technologies, 717 Potter Street, Suite 100, Berkeley, CA 94710, USA. Tel.: +1-510-848-5100; fax: +1-510- 848-5694. * Corresponding author. Tel.: +1-510-923-3758; fax: +1-510-923- 3450.