Comparison of safety and immunogenicity of two doses of investigational hepatitis B virus surface antigen co-administered with an immunostimulatory phosphorothioate oligodeoxyribonucleotide and three doses of a licensed hepatitis B vaccine in healthy adults 18–55 years of age

• Published in: Vaccine Vol. 30; no. 15; pp. 2556 - 2563
• Main Authors: Halperin, Scott A., Ward, Brian, Cooper, Curtis, Predy, Gerald, Diaz-Mitoma, Francisco, Dionne, Marc, Embree, Joanne, McGeer, Allison, Zickler, Paul, Moltz, Karl-Heinz, Martz, René, Meyer, Ingo, McNeil, Shelly, Langley, Joanne M., Martins, Eduardo, Heyward, William L., Martin, J. Tyler
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier Ltd 28.03.2012; Elsevier Limited
• Subjects: Adjuvants, Immunologic; Adolescent; Adult; adults; Age; Allergy and Immunology; Antibody response; Antigens; Autoimmune diseases; Chronic illnesses; Female; Hepatitis; hepatitis B; Hepatitis B - prevention & control; Hepatitis B Antibodies - immunology; hepatitis B antigens; Hepatitis B surface antigen; Hepatitis B Surface Antigens - administration & dosage; Hepatitis B Surface Antigens - adverse effects; Hepatitis B Surface Antigens - immunology; Hepatitis B vaccine; Hepatitis B Vaccines - administration & dosage; Hepatitis B Vaccines - adverse effects; Hepatitis B Vaccines - immunology; Hepatitis B virus; Hepatitis B virus - immunology; Humans; Immune response; Immunogenicity; Immunostimulation; Immunostimulatory sequences; Infections; injection site; Licenses; Liver cancer; Male; Middle Aged; Oligodeoxyribonucleotides - administration & dosage; Oligodeoxyribonucleotides - adverse effects; Oligodeoxyribonucleotides - immunology; Oligonucleotides; phosphorothioate; Randomized trial; surface antigens; Teenagers; Vaccines; Young Adult; Hepatitis B vaccine; Randomized trial; Immunostimulatory sequences
• ISSN: 0264-410X; 1873-2518; 1873-2518
• DOI: 10.1016/j.vaccine.2012.01.087

► Two doses of an HBV-ISS demonstrated superior immunogenicity to three doses of HBV-Eng measured at week 28. ► HBV-ISS had a safety profile that was similar to the currently licensed HBV-Eng although injection-site reactions were more common. ► HBV-ISS achieved higher levels of protection after the first and second doses. The currently licensed aluminum-hydroxide-adjuvanted hepatitis B vaccines require three doses over a 6-month period to achieve high rates of protection in adults. We compared tolerability and immunogenicity of two doses of an investigational hepatitis B vaccine using hepatitis B surface antigen adjuvanted with an immunostimulatory phosphorothioate oligodeoxyribonucleotide (HBV-ISS) to three doses of a licensed alum-adjuvanted vaccine (HBV-Eng). In this randomized, observer-blind study, healthy adults received two doses of HBV-ISS at 0 and 4 weeks or three doses of HBV-Eng at 0, 4, and 24 weeks. The primary immunogenicity endpoint was the seroprotection rate (antibody≥10mIU/mL) 8 weeks after the second dose of HBV-ISS compared to 4 weeks after the third dose of HBV-Eng. A total of 2415 participants were randomized in a ratio of 3:1 to HBV-ISS (n=1809) and HBV-Eng (n=606). The percentage of subjects exhibiting a seroprotective immune response at the primary time point was significantly higher (95.1%) for HBV-ISS than for HBV-Eng (81.1%). Superiority of the seroprotective rates for HBV-ISS was demonstrated at all time points measured. Geometric mean concentrations were also significantly higher in the HBV-ISS group at all time points measured except at week 28 (24 weeks post-second dose of HBV-ISS and 4 weeks post-third dose HBV-ISS) at which time the antibody concentrations were similar. Both vaccines were welltolerated although injection-site reactions were reported at a higher rate in HBV-ISS recipients. A short, two-dose regimen of HBV-ISS induced a superior antibody response than a three-dose regimen of a licensed hepatitis B vaccine and was well tolerated.