A phase I study of the safety and immunogenicity of recombinant hepatitis B surface antigen co-administered with an immunostimulatory phosphorothioate oligonucleotide adjuvant.
Certain oligodeoxynuclotides with CpG motifs provide enhanced immune response to co-delivered antigens. We performed a phase I, observer-blinded, randomized study in healthy anti-hepatitis B surface antigen (anti-HBsAg) antibody negative adults to explore safety and immunogenicity of co-injection of recombinant HBsAg combined with an immunostimulatory DNA sequence (ISS) 1018 ISS. Four ISS dosage groups (N=12 per group) were used: 300, 650, 1000 or 3000 microg. For each group, two controls received 20 microg HBsAg alone, two controls received ISS alone, and eight subjects received ISS+20 microg HBsAg. Subjects received two doses 8 weeks apart. Injection site reactions (tenderness and pain on limb movement) were more frequent at higher ISS+HBsAg doses but were mainly mild and of short duration. Higher anti-HBsAg antibody levels were associated with higher ISS doses. Four weeks after the first dose, a seroprotective titer (>or=10 mIU/ml) was noted for 0, 25, 75, and 87.5% of subjects by increasing ISS dose group (P<0.05) for those who received ISS+HBsAg; 1 month after the second dose this increased to 62.5, 100, 100, and 100%, respectively. Geometric mean anti-HBsAg antibody levels by increasing ISS+HBsAg dose were 1.22, 5.78, 24.75, and 206.5 mIU/ml after the first dose and 65.37, 877.6, 1545, and 3045 mIU/ml after the second dose. We conclude that 1018 ISS+HBsAg was well tolerated and immunogenic in this phase I study in healthy adults and may offer the potential for enhancement of hepatitis B virus (HBV) immunization and protection after one or two doses or in individuals who fail to respond to the standard vaccine regimen.
Halperin
Scott A
SA
Department of Pediatrics, Clinical Trials Research Center, Dalhousie University, IWK Health Centre, 5850 University Avenue, Halifax, NS, Canada B3J 3G9. shalperin@iwkgrace.ns.ca
Van Nest
Gary
G
Smith
Bruce
B
Abtahi
Simin
S
Whiley
Heather
H
Eiden
Joseph J
JJ
D000276:Adjuvants, Immunologic / Q000009:adverse effects*; D000293:Adolescent; D000328:Adult; D004305:Dose-Response Relationship, Drug; D006261:Headache / Q000139:chemically induced; D006514:Hepatitis B Surface Antigens / Q000009:adverse effects / Q000276:immunology*; D017325:Hepatitis B Vaccines / Q000009:adverse effects* / Q000276:immunology; D006801:Humans; D008875:Middle Aged; D010146:Pain / Q000139:chemically induced; D018579:Patient Selection; D013873:Thionucleotides / Q000009:adverse effects / Q000276:immunology; D013997:Time Factors; D014614:Vaccines, Synthetic / Q000009:adverse effects / Q000276:immunology
D000276:Adjuvants, Immunologic; D006514:Hepatitis B Surface Antigens; D017325:Hepatitis B Vaccines; D013873:Thionucleotides; D014614:Vaccines, Synthetic