title: The confounded effects of age and exposure history in response to influenza vaccination.
abstract: 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.
authors.affiliation: Centre for Pathogen Evolution, University of Cambridge, Department of Zoology, Downing Street, Cambridge CB2 3EJ, UK; World Health Organization Collaborating Center for Modeling, Evolution, and Control of Emerging Infectious Diseases, Cambridge CB2 3EJ, UK.
authors.forename: Ana
authors.initials: A
authors.lastname: Mosterín Höpping
authors.affiliation: Advanced Medical Research Institute of Canada, Sudbury, ON, Canada P3E 5J1.
authors.forename: Janet
authors.initials: J
authors.lastname: McElhaney
authors.affiliation: Centre for Pathogen Evolution, University of Cambridge, Department of Zoology, Downing Street, Cambridge CB2 3EJ, UK; World Health Organization Collaborating Center for Modeling, Evolution, and Control of Emerging Infectious Diseases, Cambridge CB2 3EJ, UK.
authors.forename: Judith M
authors.initials: JM
authors.lastname: Fonville
authors.affiliation: Centre for Pathogen Evolution, University of Cambridge, Department of Zoology, Downing Street, Cambridge CB2 3EJ, UK; World Health Organization Collaborating Center for Modeling, Evolution, and Control of Emerging Infectious Diseases, Cambridge CB2 3EJ, UK; Erasmus MC, Department of Viroscience, P.O. Box 2040, Ee1726, 3000 CA Rotterdam, The Netherlands; Advanced Medical Research Institute of Canada, Sudbury, ON, Canada P3E 5J1.
authors.forename: Douglas C
authors.initials: DC
authors.lastname: Powers
authors.affiliation: Erasmus MC, Department of Viroscience, P.O. Box 2040, Ee1726, 3000 CA Rotterdam, The Netherlands.
authors.forename: Walter E P
authors.initials: WEP
authors.lastname: Beyer
authors.affiliation: Centre for Pathogen Evolution, University of Cambridge, Department of Zoology, Downing Street, Cambridge CB2 3EJ, UK; World Health Organization Collaborating Center for Modeling, Evolution, and Control of Emerging Infectious Diseases, Cambridge CB2 3EJ, UK; Erasmus MC, Department of Viroscience, P.O. Box 2040, Ee1726, 3000 CA Rotterdam, The Netherlands. Electronic address: derek.smith@antigenic-cartography.org.
authors.forename: Derek J
authors.initials: DJ
authors.lastname: Smith
mesh_terms: D000293:Adolescent; D000328:Adult; D000367:Age Factors; D000368:Aged; D000369:Aged, 80 and over; D000914:Antibodies, Viral / Q000097:blood; D015986:Confounding Factors, Epidemiologic; D006801:Humans; D056724:Immunity, Humoral; D007252:Influenza Vaccines / Q000008:administration & dosage / Q000627:therapeutic use*; D007251:Influenza, Human / Q000517:prevention & control; D016014:Linear Models; D008137:Longitudinal Studies; D008875:Middle Aged; D015164:Vaccines, Inactivated / Q000008:administration & dosage / Q000627:therapeutic use; D055815:Young Adult
chemical_list: D000914:Antibodies, Viral; D007252:Influenza Vaccines; D015164:Vaccines, Inactivated
keywords: Elderly; Immunosenescence; Influenza vaccine; Repeated vaccination; Vaccine efficacy