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 adul

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• 作者：Scott A. Halperin^a ; ^{scott.halperin@dal.ca} ; Brian Ward^b ; Curtis Cooper^c ; Gerald Predy^d ; Francisco Diaz-Mitoma^e ; Marc Dionne^f ; Joanne Embree^g ; Allison McGeer^h ; Paul Zicklerⁱ ; Karl-Heinz Moltz^j ; René ; Martz^k ; Ingo Meyer^l ; Shelly McNeil^a ; Joanne M. Langley^a ; Eduardo Martins^m ; William L. Heyward^m ; J. Tyler Martin^m
• 关键词：Hepatitis B vaccine ; Immunostimulatory sequences ; Randomized trial
• 刊名：Vaccine
• 出版年：2012
• 期刊代码：89_0264410x
• 类别：imm
• 出版时间：28 March, 2012
• 卷：30
• 期：15
• 页码：2556-2563
• 文件大小：344 K

摘要

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 鈮?#xA0;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.