Healthy seropositive adults aged < 40 (n = 15), 40-64 (n = 15), and > or = 65 (n = 17) years were parenterally immunized with trivalent subvirion influenza virus vaccine, and their cellular and humoral immune responses were compared. Vaccination resulted in a significant enhancement of class I human leukocyte antigen-restricted influenza A cross-reactive cytotoxic T lymphocyte (CTL) memory. Elderly subjects had significantly lower baseline and peak postvaccination mean percentages of specific lysis of influenza A virus-infected autologous targets but nonetheless mounted CTL responses to vaccine that were comparable in magnitude to those of younger adults. Serologic responses and nasal IgG responses to each of 3 vaccine strains were reduced in magnitude and frequency with advancing age. Parenteral immunization was ineffective at inducing nasal wash IgA antibodies. Between 2 and 12 weeks after vaccination, serum and nasal antibody titers decreased modestly, although the rate of decline was comparable between age groups. The ability of elderly adults to mount CTL responses after influenza vaccination suggests that T cell effector mechanisms may be an important determinant of vaccine-induced protection against serious illness in this age group.

Numerous studies have explored whether the antibody response to influenza vaccination in elderly adults is as strong as it is in young adults. Results vary, but tend to indicate lower post-vaccination titers (antibody levels) in the elderly, supporting the concept of immunosenescence – the weakening of the immunological response related to age. Because the elderly in such studies typically have been vaccinated against influenza before enrollment, a confounding of effects occurs between age, and previous exposures, as a potential extrinsic reason for immunosenescence. We conducted a four-year study of serial annual immunizations with inactivated trivalent influenza vaccines in 136 young adults (16 to 39 years) and 122 elderly adults (62 to 92 years). Compared to data sets of previously published studies, which were designed to investigate the effect of age, this detailed longitudinal study with multiple vaccinations allowed us to also study the effect of prior vaccination history on the response to a vaccine. In response to the first vaccination, young adults produced higher post-vaccination titers, accounting for pre-vaccination titers, than elderly adults. However, upon subsequent vaccinations the difference in response to vaccination between the young and elderly age groups declined rapidly. Although age is an important factor when modeling the outcome of the first vaccination, this term lost its relevance with successive vaccinations. In fact, when we examined the data with the assumption that the elderly group had received (on average) as few as two vaccinations prior to our study, the difference due to age disappeared. Our analyses therefore show that the initial difference between the two age groups in their response to vaccination may not be uniquely explained by immunosenescence due to ageing of the immune system, but could equally be the result of the different pre-study vaccination and infection histories in the elderly.