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.
BACKGROUND
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).


METHODS
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 ≥ 10 mIU/mL) 8 weeks after the second dose of HBV-ISS compared to 4 weeks after the third dose of HBV-Eng.


RESULTS
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.


CONCLUSIONS
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.
Canadian Center for Vaccinology, Dalhousie University, IWK Health Centre, and Capital Health, Halifax, Canada. scott.halperin@dal.ca
Scott A
SA
Halperin
Brian
B
Ward
Curtis
C
Cooper
Gerald
G
Predy
Francisco
F
Diaz-Mitoma
Marc
M
Dionne
Joanne
J
Embree
Allison
A
McGeer
Paul
P
Zickler
Karl-Heinz
KH
Moltz
René
R
Martz
Ingo
I
Meyer
Shelly
S
McNeil
Joanne M
JM
Langley
Eduardo
E
Martins
William L
WL
Heyward
J Tyler
JT
Martin
D000276:Adjuvants, Immunologic; D000293:Adolescent; D000328:Adult; D005260:Female; D006509:Hepatitis B / Q000517:prevention & control*; D006510:Hepatitis B Antibodies / Q000276:immunology; D006514:Hepatitis B Surface Antigens / Q000008:administration & dosage / Q000009:adverse effects* / Q000276:immunology*; D017325:Hepatitis B Vaccines / Q000008:administration & dosage / Q000009:adverse effects* / Q000276:immunology*; D006515:Hepatitis B virus / Q000276:immunology; D006801:Humans; D008297:Male; D008875:Middle Aged; D009838:Oligodeoxyribonucleotides / Q000008:administration & dosage / Q000009:adverse effects* / Q000276:immunology*; D055815:Young Adult
D000276:Adjuvants, Immunologic; D006510:Hepatitis B Antibodies; D006514:Hepatitis B Surface Antigens; D017325:Hepatitis B Vaccines; D009838:Oligodeoxyribonucleotides; C489630:1018 oligonucleotide