Comparison of the safety and immunogenicity of hepatitis B virus surface antigen co-administered with an immunostimulatory phosphorothioate oligonucleotide and a licensed hepatitis B vaccine in healthy young adults.
BACKGROUND
Many individuals do not respond to a three-dose series of hepatitis B vaccine (HBV) and most do not achieve a protective antibody response until after dose 2 or 3.


METHODS
Healthy, seronegative 18-28 year old adults were randomly assigned in equal numbers to receive two doses of the experimental vaccine (HBV-ISS without alum) (0, 8 weeks) and placebo (24 weeks) or Engerix-B (0, 8, 24 weeks). Adverse events were collected during the first week and at 4 weeks after each injection. Antibodies were measured 4 weeks after dose 1; before, 1 and 4 weeks after dose 2, and before, 1 and 4 weeks after dose 3 and at 1 year.


RESULTS
Ninety-nine participants were enrolled (65% female; mean age 22.6 years). 79% of HBV-ISS and 12% of Engerix-B recipients had a protective antibody response 4 weeks post dose 1 (geometric mean concentration [GMC] 23.0 and 1.87 mIU/mL, respectively). By 1 week post dose 2, 100% of HBV-ISS and 18% Engerix-B recipients had protective levels (GMC 1603 versus 2.40 mIU/mL). Rates of adverse events were low and similar in both groups; headache and fatigue were the most common systemic adverse events in up to 1/3 of both groups. Mild injection-site tenderness was more common after HBV-ISS than Engerix-B after both doses (74-77% compared to 34-58%; p<or=0.029).


CONCLUSIONS
Protective levels are achieved more quickly and after fewer doses of HBV-ISS than Engerix-B. HBV-ISS is well tolerated but associated with more mild injection-site tenderness than Engerix-B.
Halperin
Scott A
SA
Clinical Trials Research Center, Dalhousie University, IWK Health Centre, 5850/5980 University Avenue, Halifax, NS, Canada B3K 6R8. scott.halperin@dal.ca
Dobson
Simon
S
McNeil
Shelly
S
Langley
Joanne M
JM
Smith
Bruce
B
McCall-Sani
Robyn
R
Levitt
Dan
D
Nest
Gary Van
GV
Gennevois
Daniel
D
Eiden
Joseph J
JJ
D000276:Adjuvants, Immunologic / Q000008:administration & dosage*; D000293:Adolescent; D000328:Adult; D005260:Female; D006510:Hepatitis B Antibodies / Q000097:blood; 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; D006801:Humans; D008297:Male; D009841:Oligonucleotides / Q000008:administration & dosage*; D013873:Thionucleotides / Q000008:administration & dosage*
D000276:Adjuvants, Immunologic; D006510:Hepatitis B Antibodies; D006514:Hepatitis B Surface Antigens; D017325:Hepatitis B Vaccines; D009841:Oligonucleotides; D013873:Thionucleotides