title: A controlled clinical trial comparing the safety and immunogenicity of a new adjuvanted hepatitis B vaccine with a standard hepatitis B vaccine.
abstract: A randomised trial was conducted in 285 adults not immune to hepatitis B (HB) to compare the safety and immunogenicity of a commercial aluminium-adjuvanted HB vaccine with and without an additional new adjuvant (AgB/RC-210-04 or AgB study groups, respectively). The additional adjuvant RC-529 is a fully synthetic monosaccharide mimetic of monophosphoryl lipid A. Subjects in the AgB/RC-210-04 (n=136) and AgB (n=149) groups were vaccinated intramuscularly on days 0, 30, and 180, according to the standard vaccination schedule for hepatitis B vaccines. Serum levels of anti-HBs were measured on days 30, 60, 90, 180, and 210. Standard safety assessments were made throughout the study period. The rates of seroprotection (anti-HBs > or =10.0 mIU/ml) were significantly greater for the AgB/RC-210-04 group at all time points: at day 90, the seroprotection rate, the primary endpoint of the trial, was 99% for AgB/RC-210-04 compared with 84% for AgB (p<0.0001). Similarly, geometric mean anti-HBs titres were significantly higher at all time points for the AgB/RC-210-04 group. There were more local reactions in the AgB/RC-210-04 group, however they were transient and this double-adjuvanted formulation was well tolerated. We conclude that the addition of a synthetic adjuvant to the AgB vaccine significantly enhanced the immunogenicity of the commercial vaccine AgB. The results indicate furthermore that a two-dose regime of the double-adjuvanted vaccine (schedule: 0-1 month) may be sufficient to achieve seroprotection in nearly 100% of individuals.
authors.affiliation: Department of Haematology, Hospital Español, Buenos Aires, Argentina.
authors.forename: Juan
authors.initials: J
authors.lastname: Dupont
authors.forename: Javier
authors.initials: J
authors.lastname: Altclas
authors.forename: Alejandro
authors.initials: A
authors.lastname: Lepetic
authors.forename: Mónica
authors.initials: M
authors.lastname: Lombardo
authors.forename: Vicente
authors.initials: V
authors.lastname: Vázquez
authors.forename: Claudia
authors.initials: C
authors.lastname: Salgueira
authors.forename: Mauricio
authors.initials: M
authors.lastname: Seigelchifer
authors.forename: Nathaly
authors.initials: N
authors.lastname: Arndtz
authors.forename: Ernesto
authors.initials: E
authors.lastname: Antunez
authors.forename: Kenneth
authors.initials: K
authors.lastname: von Eschen
authors.forename: Zbigniew
authors.initials: Z
authors.lastname: Janowicz
mesh_terms: D015060:1,2-Dipalmitoylphosphatidylcholine; D000276:Adjuvants, Immunologic; D000293:Adolescent; D000328:Adult; D015331:Cohort Studies; D004306:Dose-Response Relationship, Immunologic; D004311:Double-Blind Method; D005079:Excipients; D005260:Female; D006509:Hepatitis B / Q000276:immunology* / Q000517:prevention & control*; D006510:Hepatitis B Antibodies / Q000032:analysis / Q000096:biosynthesis; D006514:Hepatitis B Surface Antigens / Q000032:analysis / Q000276:immunology; D017325:Hepatitis B Vaccines / Q000008:administration & dosage / Q000009:adverse effects* / Q000276:immunology*; D006801:Humans; D008297:Male; D013535:Suspensions
chemical_list: D000276:Adjuvants, Immunologic; D005079:Excipients; D006510:Hepatitis B Antibodies; D006514:Hepatitis B Surface Antigens; D017325:Hepatitis B Vaccines; D013535:Suspensions; D015060:1,2-Dipalmitoylphosphatidylcholine