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Hepatitis B Immunization of Healthy Elderly Adults: Relationship between Na¨ıve CD4+ T Cells and Primary Immune Response and Evaluation of GM-CSF as an Adjuvant

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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. Na¨ıve 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 μg or 250 μg 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). Na¨ıve 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. Na¨ıve 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 na¨ıve, 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 × age in years) + (0.031 × % na¨ıve CD4T cells) + 2.68; adjusted r2 = 0.605 and P < 0.0001. However, age had a larger effect than na¨ıve 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 na¨ıve CD4 T cells. Thus, there was a large effect of age that could not be explained by the quantitative change in the na¨ıve T-helper cells.

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Authors and Affiliations

  1. Department of Medicine, University of Rochester School of Medicine and Dentistry, Rochester, New York

    R. John Looney, Muhammad S. Hasan, Denise Coffin, Deborah Campbell, Ann R. Falsey, George N. Abraham & Thomas G. Evans

  2. Department of Biostatistics, University of Rochester School of Medicine and Dentistry, Rochester, New York

    John Kolassa

  3. Immunex Corporation, Seattle, Washington

    Jan M. Agosti

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  1. R. John Looney
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  2. Muhammad S. Hasan
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  3. Denise Coffin
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  4. Deborah Campbell
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  5. Ann R. Falsey
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  8. George N. Abraham
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  9. Thomas G. Evans
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Looney, R.J., Hasan, M.S., Coffin, D. et al. Hepatitis B Immunization of Healthy Elderly Adults: Relationship between Na¨ıve CD4+ T Cells and Primary Immune Response and Evaluation of GM-CSF as an Adjuvant. J Clin Immunol 21, 30–36 (2001). https://doi.org/10.1023/A:1006736931381

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