Vaccine Trials in Human Subjects
Friday, 1:30 - 3:30 pm
Background: HIV patients are hyporesponsive to vaccination, including hepatitis B virus (HBV). CPG 7909 is an oligodeoxynucleotide, containing immunostimulatory CpG motifs, that directly activates via TLR9 human B cells and plasmacytoid dendritic cells. We previously reported rapid, higher, and sustained HBV seroprotection (to 48 weeks) and increases HBV-specific T helper cell response in HIV subjects receiving Engerix-B plus 1 mg CPG 7909.
Methods: A randomized,
double-blind controlled trial was conducted to determine clinical safety and
HBV immunogenicity in adult HIV subjects on effective
antiretroviral therapy. HBV susceptible subjects, half of whom had failed
previous vaccination, were vaccinated at 0, 1, and 2 months with a double adult
dose of Engerix-B ± 1 mg CPG 7909 (n = 38). Seroprotective titres (SP, anti-HBs titre ≥10 mIU/mL) at 24, 30, and 36 months are reported. Missing
values between measures were interpolated. Fisher exact test was used to
generate the p values using
Results: Geometric mean anti-HBs titres were higher in the CPG than placebo control adjuvant group at all measured time points. The proportion retaining SP was greater in CPG 7909 recipients at 24 (14 of 15 CPG vs 10 of 18 controls, p = 0.021), 30 (13 of 14 CPG vs 7 of 15 controls, p = 0.014), and 36 months (10 of 11 CPG vs 4 of 13 controls, p = 0.005). The proportion retaining SP was greater in CPG recipients for both prior vaccine failures and vaccine naļves. More CPG-Engerix subjects than controls had durable high-titre anti-HBs response (≥ 100 mIU/mL) at 24 months (9 of 14 CPG vs 3 of 18 controls, p = 0.010), 30 months (7 of 14 CPG vs 2 of 15 controls, p = 0.050), and 36 (5 of 11 CPG vs 2 of 13 controls, p = 0.182).
Conclusions: The immunostimulatory properties of CPG 7909 present an important strategy in achieving long-term hepatitis B seroprotection in HBV vaccine hyporesponsive populations.
Keywords: immune modulator; hepatitis B; vaccine