Granulocyte Macrophage Colony–Stimulating Factor as an Adjuvant for Hepatitis B Vaccination of Healthy Adults
ABSTRACT Granulocyte macrophage colony-stimulating factor (GM-CSF) has shown promise as an adjuvant to improve the kinetics and magnitude of the immune response after vaccination. It was hypothesized that GM-CSF given intramuscularly (IM) with hepatitis B vaccine would result in increased seroconversion rates and antibody titers. In total, 108 healthy volunteers (18-45 years old) received recombinant hepatitis B vaccine IM at 0, 1, and 6 months and were randomized to receive either concurrent GM-CSF (80 or 250 microgram) or placebo IM with the first two vaccinations. The percentages of subjects achieving a protective level of antibody at day 56 were 58.3%, 58.8%, and 58.3% in the placebo and 80- and 250-microgram GM-CSF arms, respectively. The geometric mean titers of antibody measured on days 28, 56, and 189 were not statistically different between arms. GM-CSF given immediately before recombinant hepatitis B vaccination was safe and well tolerated but did not appear to provide significant adjuvant activity at this dose.
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- "All the included studies were described as randomized, but the method to generate the sequence was described and appropriate in four studies only    . Three studies were defined as double blind, and one as single blind    . Only the study defined as a single blind trial clearly reported concealment of treatment allocation  "
ABSTRACT: The efficacy of granulocyte macrophage colony-stimulating factor (GM-CSF) to enhance the immune response to hepatitis B virus vaccine has been object of several reports. We searched for randomized controlled clinical trials comparing GM-CSF given concomitantly to hepatitis B virus vaccine to vaccine given alone or with placebo. Data on rates of seroconversion (anti-HBs titers >10 IU/ml) from 13 studies (734 subjects) produced combined estimates that favored GM-CSF as compared to controls: rate ratio after a single immunization was 1.54 [95% confidence interval (CI), 1.04-2.27] and 1.20 (95% CI, 1.02-1.42) at the end of the vaccination cycle. Using a logistic approach a significant dose/response effect of GM-CSF was seen. Moreover, in renal failure patients who have responded to the vaccine, GM-CSF increased anti-HBs titers. Our findings suggest that GM-CSF induced a significant effect in terms of response rate and achievement of an earlier seroconversion to the vaccine in the overall populations examined, in renal failure patients and in healthy individuals.Vaccine 01/2007; 25(4):709-18. DOI:10.1016/j.vaccine.2006.08.015 · 3.49 Impact Factor
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ABSTRACT: The efficacy of granulocyte-macrophage colony-stimulating factor (GM-CSF) to enhance the primary immune response to hepatitis B vaccine was studied in healthy elderly with young volunteers included as controls in this double-blind, placebo-controlled trial of GM-CSF as an immune adjuvant. Naïve T-helper cells (CD4+CD45RA+) were determined at baseline. Forty-five healthy elderly (average age, 74 years) and 37 healthy young controls (average age, 28 years) were randomized. Hepatitis B vaccine was administered at 0, 1, and 6 months. GM-CSF as a single injection of either 80 microg or 250 microg with the first and second doses of hepatitis B vaccine. In this trial GM-CSF did not enhance antibody responses. However, the antibody responses were dramatically different between these two groups: 35/35 young developed a protective titer versus 19/45 elderly (P < 0.0001). In addition, the mean logarithm of anti-hepatitis B antibody level in the 35 young who completed the study was 3.17 (log mIU/ml) but only 2.21 in the 19 elderly responders (P < 0.0001). Naïve T-helper cells differed significantly between the two groups: the mean percentage of CD4+CD45RA+ T cells was 47.9% versus 35.0% (P < 0.0001) in the young and elderly volunteers respectively. Naïve T cells also differed significantly between elderly who did or did not respond to HBV (39.9% vs. 31.7%, P = 0.039). Using linear regression, age, and percent naive, CD4 T cells were determined to significantly influence the anti-hepatitis B antibody response, but sex and dose of GM-CSF did not. For a two-parameter model: logarithm of antibody titer = (-0.038 x age in years) + (0.031 x % naïve CD4T cells) + 2.68; adjusted r2 = 0.605 and P < 0.0001. However, age had a larger effect than naive CD4 T cells, i.e., in comparing young and elderly groups the log antibody titer decreased by 1.73 due to the increase in age but only 0.40 due to the decrease in naive CD4 T cells. Thus, there was a large effect of age that could not be explained by the quantitative change in the naïve T-helper cells.Journal of Clinical Immunology 01/2001; 21(1):30-6. DOI:10.1023/A:1006736931381 · 2.65 Impact Factor