BACKGROUND:  Non-protective response to HBV vaccine occurs in HIV infection. CpG oligodeoxynucleotide 7909 activates plasmacytoid dendritic cell function and promotes Th-1 biased immune response, may greatly increase immunogenicity of vaccination in general, and may restore vaccine responsiveness in hyporesponsive persons.

METHODS: In a phase Ib/IIa randomised, double-blind controlled clinical trial, we compared CpG 7909 versus placebo adjuvant in HBV vaccination with alum-adsorbed yeast-derived recombinant hepatitis B surface antigen (HBs) for safety, tolerance, and vaccine adjuvancy.  58 adult volunteers with HIV infection on HAART, HIV RNA < 50 copies/mL and CD4 > 200 /:L were screened.  38 susceptible anti-HBs seronegatives (19 HBV vaccine naïve, 19 HBV vaccine failures) were vaccinated at 0, 1 and 2 months with divided IM injection of double-dose Engerix-B®  (SmithKline Beecham) total 40:g, with CpG 7909 total 1mg or placebo; 20 other immune anti-HBs seropositive subjects received only CpG 7909 or placebo, all allocated randomly within groups by HBV vaccine status.  Outcomes were serially measured over 24 weeks follow-up.

RESULTS:  Vaccinees had good local and systemic tolerance.  One subject experienced urticaria.  CD4 T lymphocyte counts and suppression of HIV plasma viremia were sustained.   In 19 susceptible control vaccinees, seroconversion (SC, anti-HBs titre > 1 mIU/mL) and seroprotection (SP, anti-HBs titre > 10 mIU/mL) occurred by week 6 (74% SC, 53% SP), by week 8 (84% SC, 53% SP), and by week 12 (100% SC, 95% SP).  In 19 with CpG adjuvant, SP occurred significantly earlier by week 6 (95% SC, 89% SP, p=0.029), by week 8 (95% SC, 89% SP, p=0.029), and by week 12 (94% SC, 94% SP).  At all 5 time points over 24 weeks from first dose, mean anti-HBs titres were higher in the CpG group.  In 19 vaccinees with prior vaccine failure, significantly more in the CpG group had durable high-titre anti-HBs response (> 100 mIU/mL) at 24 weeks (67% CpG versus 10% control, p = 0.020).

CONCLUSION: This small controlled study shows safety and tolerance of CpG 7909 as adjuvant to accelerated double-dose Engerix-B in treated HIV infection.  HBV susceptible CpG groups had significantly more rapid attainment of SP, reached and maintained higher anti-HBs titres.  In prior HBV vaccine failures, significantly more in the CpG group maintained durable high-titre protection.