The confounded effects of age and exposure history in response to influenza vaccination.

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.

Safety and immunogenicity of haemophilus influenzae type B polysaccharide or conjugate vaccines in an elderly adult population.

OBJECTIVES: To evaluate the safety and immunogenicity of unconjugated Haemophilus influenzae type b (Hib) polysaccharide (PRP) vaccine and two PRP-protein-conjugated vaccines as a model for the comparison of protein-conjugated versus plain polysaccharide vaccines in the elderly. DESIGN: Randomized, double-blind, prospective study. SETTING: University-based center for vaccine research and development. PARTICIPANTS: A total of 125 adults, aged 64 to 92, who were judged to be in general good health and lacking any significant underlying medical conditions. INTERVENTION: Subjects were randomized to receive one of three vaccines: Group 1 (n=39), PRP; Group 2 (n=44), PRP conjugated to an outer-membrane protein complex of Neisseria meningitidis (PRP-OMP); and Group 3 (n=42), PRP conjugated to diphtheria toxoid (PRP-D). Sera were obtained before immunization and 1 and 12 months later. MEASUREMENTS: Subjects maintained a diary of injection site and systemic reactions for 3 days after immunization. A radioantigen-binding assay was used to measure total concentrations of serum anticapsular antibody, and an enzyme-linked immunosorbent assay was used to measure immunoglobulin (Ig) G1 and IgG2 anticapsular antibody responses. Antibody functional activity was assessed using a complement-mediated bactericidal assay. RESULTS: Before vaccination, the geometric mean serum anticapsular antibody concentration was 0.8 microg/mL, but fewer than 10% of subjects had detectable bactericidal activity (titer>1:4). The magnitude, subclass distribution, and bactericidal activity of antibody responses to unconjugated PRP vaccine were similar to those observed in previous studies of younger adults immunized with PRP. The OMP conjugate, which is highly immunogenic after one dose in 2-month old infants, did not elicit anticapsular antibody responses in the elderly greater than those elicited by PRP vaccine (P=.43). In contrast, the D conjugate, which is poorly immunogenic in 2-month old infants, elicited higher anticapsular antibody responses than PRP vaccine in the elderly (P=.01) and higher levels than the OMP-conjugate 1 year after vaccination (P<.006). CONCLUSION: Elderly adults develop protective anticapsular antibody responses to unconjugated and conjugated PRP vaccine. The higher anticapsular antibody responses to the D conjugate but not to the OMP conjugate in the elderly, which is the reverse of that observed in immunized infants, implies fundamental differences in the immunological mechanisms by which the two age groups respond to PRP and by which the OMP and D conjugates elicit anticapsular antibody responses.