Safety and immunogenicity of different two-dose regimens of an investigational hepatitis B vaccine (hepatitis B surface antigen co-administered with an immunostimulatory phosphorothioate oligodeoxyribonucleotide) in healthy young adults.
BACKGROUND
Previous studies have shown that two doses of an investigational hepatitis B vaccine consisting of hepatitis B surface antigen combined with an immunostimulatory phosphorothioate oligodeoxyribonucleotide adjuvant (HBV-ISS) given 8 weeks apart provides seroprotection sooner than 3 doses of a licensed hepatitis B vaccine over 24 weeks. A more rapid schedule with a 4-week interval could provide earlier protection and potentially greater compliance.


METHODS
In this randomized, double-blind study, healthy adults received two doses of HBV-ISS at 0 and 4 or 0 and 8 weeks; saline placebo was given at week 8 for the 0-4 schedule and at week 4 for the 0-8 schedule). Adverse events were collected after each dose. Antibodies were measured at 0, 4, 8, 12, and 32 weeks.


RESULTS
Participants were randomized to the 0-4 (n=18) or 0-8 (n=23) weeks schedule. Rates of adverse events were similar in the two groups after the HBV-ISS injections regardless of the schedule, but more frequent than after the placebo injections. By 4 weeks post-dose-2, 94.1% of 0-4 and 100% of 0-8 recipients had protective antibody levels; geometric mean concentrations were 244 mIU/mL and 3217 mIU/mL respectively. By 32 weeks, the difference in antibody concentration had decreased (GMC 439 mIU/mL vs. 863 mIU/mL, respectively; p=0.04).


CONCLUSIONS
A 0-4 weeks, two-dose regimen of HBV-ISS was well-tolerated and induced an antibody response that was similar to a 0-8 weeks schedule.
Canadian Center for Vaccinology, Dalhousie University, IWK Health Centre, and Capital Health, Halifax, Nova Scotia, Canada. scott.halperin@dal.ca
Scott A
SA
Halperin
Shelly
S
McNeil
Joanne M
JM
Langley
Bruce
B
Smith
Donna
D
MacKinnon-Cameron
Robyn
R
McCall-Sani
William L
WL
Heyward
J Tyler
JT
Martin
D000276:Adjuvants, Immunologic / Q000008:administration & dosage*; D000328:Adult; D005260:Female; D006510:Hepatitis B Antibodies / Q000276:immunology; D006514:Hepatitis B Surface Antigens / Q000737:chemistry / Q000276:immunology*; D017325:Hepatitis B Vaccines / Q000008:administration & dosage / Q000009:adverse effects* / Q000276:immunology*; D006801:Humans; D008297:Male; D009838:Oligodeoxyribonucleotides / Q000008:administration & dosage* / Q000737:chemistry / Q000276:immunology; D054735:Phosphorothioate Oligonucleotides / Q000008:administration & dosage; D055815:Young Adult
D000276:Adjuvants, Immunologic; D006510:Hepatitis B Antibodies; D006514:Hepatitis B Surface Antigens; D017325:Hepatitis B Vaccines; D009838:Oligodeoxyribonucleotides; D054735:Phosphorothioate Oligonucleotides