Cytotoxic T lymphocyte responses to a liposome-adjuvanted influenza A virus vaccine in the elderly.

This randomized double-blind study evaluated cytotoxic T lymphocyte (CTL) responses of elderly volunteers after parenteral immunization with either liposome-adjuvanted (n = 23) or control subvirion (n = 26) vaccine containing detergent-split influenza A/Taiwan/1/86 (H1N1) virus. Peripheral blood mononuclear cells obtained 0, 2, and 12 weeks after vaccination were stimulated in vitro with influenza A (H1N1) virus-infected autologous cells and then assayed for influenza virus-specific cytotoxicity using autologous virus-infected target cells. CTL responses to vaccination exhibited influenza A virus heterosubtypic cross-reactivity and were mediated primarily by CD8+ effector cells. Anti-influenza virus CTL activity was enhanced to a significantly greater extent by the liposome vaccine than by the control subvirion vaccine. It remains to be established whether the advantage of a liposomal formulation in terms of an improved CTL response is relevant to vaccine protective efficacy.

In previously immunized elderly adults inactivated influenza A (H1N1) virus vaccines induce poor antibody responses that are not enhanced by liposome adjuvant.

In a randomized, double-blinded study, 77 healthy elderly seropositive volunteers (95% of whom had received influenza vaccine within the prior 5 years) were immunized with either monovalent liposome-adjuvanted or control subvirion vaccine containing inactivated influenza A/Taiwan/1/86 (H1N1) virus. The experimental vaccine was well-tolerated but elicited serologic responses that were no different in frequency or magnitude from those induced by the control vaccine. Less than 20% of subjects in either group mounted a fourfold or greater rise in antibody titer. Sixty-three elderly subjects who had participated in the liposome vaccine trial were reimmunized 18 weeks later with licensed trivalent subvirion vaccine, and their serologic responses were compared with those of 26 young adults. Significant rises in hemagglutination inhibition (HAI) antibody titers to the A/Texas/36/91 (H1N1), A/Beijing/32/92 (H3N2) and B/Panama/45/90 components occurred in 10%, 76% and 56% of elderly vaccinees, respectively, compared to 92% (p < 0.0001), 100% (p < 0.005) and 88% (p < 0.005) of young vaccines, respectively. Age differences in seroresponse rates to the H1N1 subtype antigen were significant even when comparing young and old adults with identical prevaccination HAI antibody titers. These data confirm prior observations suggesting that previously immunized elderly persons have impaired serologic responses to influenza vaccines, particularly against recently circulating H1N1 subtype antigens. It remains unclear whether liposome-adjuvanted formulations would have an advantage over conventional influenza vaccines for routine annual reimmunization of targeted populations.