CPG 7909 adjuvant improves hepatitis B virus vaccine seroprotection in antiretroviral-treated HIV-infected adults

• Published in: AIDS (London) Vol. 19; no. 14; pp. 1473 - 1479
• Main Authors: Cooper, Curtis L, Davis, Heather L, Angel, Jonathan B, Morris, Mary Lou, Elfer, Sue M, Seguin, Isabelle, Krieg, Arthur M, Cameron, D William
• Format: Journal Article
• Language: English
• Published: England 23.09.2005
• Subjects: Adjuvants, Immunologic - therapeutic use; Adolescent; Adult; Antiretroviral Therapy, Highly Active - adverse effects; CD4 Lymphocyte Count; Double-Blind Method; Female; Hepatitis B - complications; Hepatitis B - immunology; Hepatitis B - prevention & control; Hepatitis B Surface Antigens - blood; Hepatitis B Vaccines - administration & dosage; Hepatitis B Vaccines - adverse effects; Hepatitis B Vaccines - immunology; Hepatitis B virus; HIV Infections - complications; HIV Infections - drug therapy; HIV Infections - immunology; Human immunodeficiency virus; Humans; Lymphocyte Activation; Male; Middle Aged; Oligodeoxyribonucleotides - therapeutic use; RNA, Viral - blood; Vaccines, Synthetic - administration & dosage; Vaccines, Synthetic - adverse effects; Vaccines, Synthetic - immunology
• ISSN: 0269-9370
• DOI: 10.1097/01.aids.0000183514.37513.d2

HIV patients are vaccine hyporesponsive. 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 > or = 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. 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 (> or = 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 = 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). 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.