title: Hepatitis B immunization of healthy elderly adults: relationship between naïve CD4+ T cells and primary immune response and evaluation of GM-CSF as an adjuvant.
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.
authors.affiliation: Department of Medicine, University of Rochester School of Medicine and Dentistry, New York, USA.
authors.forename: R J
authors.initials: RJ
authors.lastname: Looney
authors.forename: M S
authors.initials: MS
authors.lastname: Hasan
authors.forename: D
authors.initials: D
authors.lastname: Coffin
authors.forename: D
authors.initials: D
authors.lastname: Campbell
authors.forename: A R
authors.initials: AR
authors.lastname: Falsey
authors.forename: J
authors.initials: J
authors.lastname: Kolassa
authors.forename: J M
authors.initials: JM
authors.lastname: Agosti
authors.forename: G N
authors.initials: GN
authors.lastname: Abraham
authors.forename: T G
authors.initials: TG
authors.lastname: Evans
mesh_terms: D000276:Adjuvants, Immunologic / Q000494:pharmacology*; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015496:CD4-Positive T-Lymphocytes / Q000502:physiology*; D004311:Double-Blind Method; D005260:Female; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000494:pharmacology*; D006510:Hepatitis B Antibodies / Q000097:blood; D017325:Hepatitis B Vaccines / Q000276:immunology*; D006801:Humans; D007114:Immunization; D008297:Male; D012044:Regression Analysis
chemical_list: D000276:Adjuvants, Immunologic; D006510:Hepatitis B Antibodies; D017325:Hepatitis B Vaccines; D016178:Granulocyte-Macrophage Colony-Stimulating Factor