The effect of DHEAS on influenza vaccination in aging adults

OBJECTIVE: To determine whether simultaneous administration of dehydroepiandrosterone sulfate (DHEAS) exhibits adjuvant activity in the immune response of aging humans by supplementing influenza vaccination with the maximum single dose of DHEAS that could be practically injected subcutaneously (approximately 7.5 mg). DESIGN: A randomized, double-blind, placebo-controlled trial of DHEAS injection with 1993-94 and 1994-95 influenza vaccine in older subjects. In addition, initial safety, tolerability, and control testing with 1993-94 influenza vaccine was conducted in young subjects. SETTING: An urban primary care geriatrics clinic. PARTICIPANTS: Seventy-eight older adult volunteers (mean age 78.61 +/- 3.43 years, range 73-90 years) and 20 younger controls (<40 years, means age 32.76 +/- 5.39 years) were recruited from clinic and community advertising. Subjects were free of disease or medication known to affect immune function. MEASUREMENTS: Immune responses to vaccine at 0, 2, and 4 weeks were measured by vaccine antigen-induced lymphoproliferation in peripheral blood mononuclear cells (PBMC) and serum antibody response by hemagglutination inhibition (HI). RESULTS: The maximum DHEAS dose that could be practically administered subcutaneously was 7.5 mg. Baseline DHEAS levels were significantly lower in older adults (52.1 vs 236.4 mu g/dL, P <.001). The 1993 old adult DHEAS group HI response tended to be higher for the H3N2 Beijing antigen but not for the H1N1 or B antigen. In subjects with HI titers less then 1:40 for the H3N2 Beijing antigen (n = 29), the post-vaccination titer response tended to be higher among the 16 subjects who received DHEAS (P =.06). The peak response for the H3N2 antigen was associated with the initial DHEAS serum concentration in the DHEAS and placebo groups (R-2 =.22, P =.04 and R-2 =.21, P =.06, respectively). No significant differences were found for antibody responses to the H1N1 and B antigens or vaccine-antigen induced lymphoproliferation. CONCLUSION: A one-time supplemental dose of DHEAS with influenza vaccination appeared to enhance the specific HI antibody response to the 1993-94 H3N2 antigen in a small group of older adults. These findings were limited to those with lower prevaccination titers and lower DHEAS concentrations. Although clinical implications of these findings for influenza vaccine are uncertain, these results suggest additional detailed immunologic investigations on the role of DHEAS in the aging human immune response are warranted.