The safety and efficacy of GM-CSF as an adjuvant in hepatitis B vaccination of chronic hemodialysis patients who have failed primary vaccination

Background: End-stage renal disease and the need for chronic hemodialysis i s an indication for hepatitis B vaccination, but up to half of dialysis pat ients fail to respond to a 40 mu g/dose i.m. three-dose primary series of r ecombinant hepatitis B vaccine. Only another 10 - 20% respond to additional boosting doses of vaccine. Patients and methods: Since GM-CSF has been sho wn 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 hemodialys is patients. Patients with negative hepatitis B surface antibody and antige n who had received at least three doses of recombinant hepatitis B vaccine without response (antibody titre < 10 mIU/ml) were randomized to placebo, 4 0 mu g, or 80 mu g of GM-CSF given with 40 mu g recombinant hepatitis B vac cine i.m. at the same site. Clinical and laboratory studies for safety asse ssment were done on days 1 and 3, and hepatitis B surface antibody titres w ere measured at baseline and days 21 and 1 80 after the study injections. R esults. No significant local or systemic toxicity was noted from the co-inj ections. The rates of response and geometric mean titre (GMT) were equivale nt among all three study groups: placebo 6/10 developed antibodies. GMT 22. 1 mIU/ml; 40 mu g GM-CSF 3710 developed antibodies, GMT 5.4 mIU; and 80 mu g GM-CSF 3/8 developed antibodies, GMT 9.7 mIU/ml. Six months after vaccina tion, antibody titres were available for 11 of the 12 day 21 positive respo nders; only 4 of these 11 patients remained antibody positive at 6 months. Conclusion: GM-CSF given in a single 40 mu g and 80 mu g i.m, dose was nor an effective adjuvant with hepatitis B vaccine in chronic hemodialysis pati ents who had previously failed to respond to hepatitis B immunization.