title: The safety and efficacy of GM-CSF as an adjuvant in hepatitis B vaccination of chronic hemodialysis patients who have failed primary vaccination.
abstract: BACKGROUND
  End-stage renal disease and the need for chronic hemodialysis is an indication for hepatitis B vaccination, but up to half of dialysis patients fail to respond to a 40 microg/dose i.m. three-dose primary series of recombinant hepatitis B vaccine. Only another 10-20% respond to additional boosting doses of vaccine.
  
  
  METHODS
  Since GM-CSF has been shown to be an effective adjuvant for hepatitis B vaccine in healthy subjects and multiple animal vaccine models, we conducted a randomized, double-blind trial of GM-CSF with recombinant hepatitis B vaccine in chronic hemodialysis patients. Patients with negative hepatitis B surface antibody and antigen who had received at least three doses of recombinant hepatitis B vaccine without response (antibody titre < 10 mIU/ml) were randomized to placebo, 40 microg, or 80 microg of GM-CSF given with 40 microg recombinant hepatitis B vaccine i.m. at the same site. Clinical and laboratory studies for safety assessment were done on days 1 and 3, and hepatitis B surface antibody titres were measured at baseline and days 21 and 180 after the study injections.
  
  
  RESULTS
  No significant local or systemic toxicity was noted from the co-injections. The rates of response and geometric mean titre (GMT) were equivalent among all three study groups: placebo 6/10 developed antibodies, GMT 22.1 mIU/ml; 40 microg GM-CSF 3/10 developed antibodies, GMT 5.4 mIU; and 80 microg GM-CSF 3/8 developed antibodies, GMT 9.7 mIU/ml. Six months after vaccination, antibody titres were available for 11 of the 12 day 21 positive responders; only 4 of these 11 patients remained antibody positive at 6 months.
  
  
  CONCLUSIONS
  GM-CSF given in a single 40 microg and 80 microg i.m. dose was not an effective adjuvant with hepatitis B vaccine in chronic hemodialysis patients who had previously failed to respond to hepatitis B immunization.
authors.affiliation: Infectious Diseases, University of Rochester School of Medicine and Dentistry and Highland Hospital, NY, USA.
authors.forename: T G
authors.initials: TG
authors.lastname: Evans
authors.forename: M
authors.initials: M
authors.lastname: Schiff
authors.forename: B
authors.initials: B
authors.lastname: Graves
authors.forename: J
authors.initials: J
authors.lastname: Agosti
authors.forename: M L
authors.initials: ML
authors.lastname: Barritt
authors.forename: D
authors.initials: D
authors.lastname: Garner
authors.forename: J L
authors.initials: JL
authors.lastname: Holley
mesh_terms: D000276:Adjuvants, Immunologic / Q000008:administration & dosage*; D000328:Adult; D004311:Double-Blind Method; D005260:Female; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000008:administration & dosage* / Q000276:immunology; D006509:Hepatitis B / Q000517:prevention & control*; D006510:Hepatitis B Antibodies / Q000032:analysis; D017325:Hepatitis B Vaccines / Q000008:administration & dosage* / Q000276:immunology; D006801:Humans; D008297:Male; D008875:Middle Aged; D006435:Renal Dialysis; D014611:Vaccination
chemical_list: D000276:Adjuvants, Immunologic; D006510:Hepatitis B Antibodies; D017325:Hepatitis B Vaccines; D016178:Granulocyte-Macrophage Colony-Stimulating Factor