CPG 7909 adjuvant improves hepatitis B virus vaccine seroprotection in antiretroviral-treated HIV-infected adults Curtis L. Cooper a , Heather L. Davis b , Jonathan B. Angel a , Mary Lou Morris b , Sue M. Elfer b , Isabelle Seguin a , Arthur M. Krieg c and D. William Cameron a Background: HIV patients are vaccine hyporesponsive. Methods: We evaluated CPG 7909, a synthetic oligodeoxynucleotide containing immunostimulatory CpG motifs, as an adjuvant to Engerix-B. A randomized, double-blind controlled trial was conducted to determine safety and hepatitis B virus (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 dose of Engerix-B with/without () 1 mg CPG 7909. HBV immune subjects (anti-HBsAg titres  10 mIU/l) received either CPG 7909 alone or saline. Safety, anti-HBs titres and lymphocyte proliferation response (LPR) to HBsAg were assessed over 12 months. Results: Vaccinations with Engerix B  CPG 7909 were well tolerated locally and systemically. HIV suppression and CD4 cell counts were maintained. Anti-HBs titers were significantly higher in vaccinees receiving CPG 7909, for all time points after the second dose. Seroprotective titres ( 10 mIU/ml) by 6 and 8 weeks, and 12 months were found in 89, 89, and 100% of subjects receiving CPG 7909 compared to 53, 42, and 63% of controls respectively (P ¼ 0.029, 0.005, and 0.008). HBsAg LPR was increased at all time-points up to 12 months after vaccination with addition of CPG 7909 (P < 0.05). Conclusions: Addition of CPG 7909 achieves rapid, higher, and sustained HBV seroprotection and increases HBV-specific T helper cell response to HBV vaccine in HIV subjects. These results confirm a potential adjuvant role for CPG 7909 in vaccine hyporesponsive populations including those living with HIV. ß 2005 Lippincott Williams & Wilkins AIDS 2005, 19:1473–1479 Keywords: CpG oligodeoxynucleotides, HIV, hepatitis B virus, vaccine, adjuvant Introduction HIV-infected individuals are at increased risk of hepatitis B virus (HBV) infection due to shared modes of transmission. Furthermore, when infected with HBV, HIV-infected individuals are more likely to become chronic carriers [1] and develop complications such as cirrhosis and hepatocellular carcinoma [2,3]. Thus HIV-infected patients have a special need for effective HBV vaccination. By virtue of immune deficiency, HIV-infected individuals From the a Division of Infectious Diseases, University of Ottawa at The Ottawa Hospital, Ottawa Health Research Institute, Ottawa, the b Coley Pharmaceutical Canada, Ottawa, Ontario, Canada, and the c Coley Pharmaceutical Group, Wellesley, Massachusetts, USA. Correspondence to Curtis Cooper, MD, FRCPC, Room G12, 501 Smyth Road, The Ottawa Hospital-General Campus, Ottawa, ON, K1H 8L6, Canada. E-mail: ccooper@ottawahospital.on.ca Received: 20 January 2005; accepted: 13 June 2005. ISSN 0269-9370 Q 2005 Lippincott Williams & Wilkins 1473