title: CPG 7909 adjuvant improves hepatitis B virus vaccine seroprotection in antiretroviral-treated HIV-infected adults.
abstract: 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 > 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.
  
  
  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 (> 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).
  
  
  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.
authors.affiliation: Division of Infectious Diseases, University of Ottawa at The Ottawa Hospital, Ottawa Health Research Institute, 501 Smyth Road, Ottawa, Ontario K1H 8L6, Canada. ccooper@ottawahospital.on.ca
authors.forename: Curtis L
authors.initials: CL
authors.lastname: Cooper
authors.forename: Heather L
authors.initials: HL
authors.lastname: Davis
authors.forename: Jonathan B
authors.initials: JB
authors.lastname: Angel
authors.forename: Mary Lou
authors.initials: ML
authors.lastname: Morris
authors.forename: Sue M
authors.initials: SM
authors.lastname: Elfer
authors.forename: Isabelle
authors.initials: I
authors.lastname: Seguin
authors.forename: Arthur M
authors.initials: AM
authors.lastname: Krieg
authors.forename: D William
authors.initials: DW
authors.lastname: Cameron
mesh_terms: D000276:Adjuvants, Immunologic / Q000627:therapeutic use*; D000293:Adolescent; D000328:Adult; D023241:Antiretroviral Therapy, Highly Active / Q000009:adverse effects; D018791:CD4 Lymphocyte Count; D004311:Double-Blind Method; D005260:Female; D015658:HIV Infections / Q000150:complications / Q000188:drug therapy* / Q000276:immunology; D006509:Hepatitis B / Q000150:complications / Q000276:immunology / Q000517:prevention & control*; D006514:Hepatitis B Surface Antigens / Q000097:blood; D017325:Hepatitis B Vaccines / Q000008:administration & dosage* / Q000009:adverse effects / Q000276:immunology; D006801:Humans; D008213:Lymphocyte Activation; D008297:Male; D008875:Middle Aged; D009838:Oligodeoxyribonucleotides / Q000627:therapeutic use*; D012367:RNA, Viral / Q000097:blood; D014614:Vaccines, Synthetic / Q000008:administration & dosage* / Q000009:adverse effects / Q000276:immunology
chemical_list: D000276:Adjuvants, Immunologic; C075654:Engerix-B; D006514:Hepatitis B Surface Antigens; D017325:Hepatitis B Vaccines; D009838:Oligodeoxyribonucleotides; C483020:ProMune; D012367:RNA, Viral; D014614:Vaccines, Synthetic