Vaccine 24 (2006) 1159–1169 Antibody response to influenza vaccination in the elderly: A quantitative review Katherine Goodwin a , C´ ecile Viboud b , Lone Simonsen a,∗ a National Institutes of Allergy and Infectious Diseases, Office of Global Affairs, 6610 Rockledge Drive, Room 2033, Bethesda, MD 20818, USA b Fogarty International Center, National Institutes of Health, Bethesda, MD, USA Received 2 June 2005; received in revised form 17 August 2005; accepted 26 August 2005 Available online 19 September 2005 Abstract We performed a quantitative review of 31 vaccine antibody response studies conducted from 1986 to 2002 and compared antibody responses to influenza vaccine in groups of elderly versus younger adults. We did a weighted analysis of the probability of vaccine response (measured as seroconversion and seroprotection) for each vaccine component (H1, H3 and B antigens). Using a multiple regression model, we adjusted for factors that might affect the vaccine response. The adjusted odds-ratio (OR) of responses in elderly versus young adults ranged from 0.24 to 0.59 in terms of seroconversion and seroprotection to all three antigens. The CDC estimates of 70–90% clinical vaccine efficacy in young adults and these estimates suggest a corresponding clinical efficacy in the elderly of 17–53% depending on circulating viruses. We conclude that the antibody response in the elderly is considerably lower than in younger adults. This highlights the need for more immunogenic vaccine formulations for the elderly. © 2005 Elsevier Ltd. All rights reserved. Keywords: Influenza vaccine; Antibodies; Aging/immunology; Review 1. Introduction Influenza is an increasingly common cause of hospitaliza- tion and death in the elderly [1]. In recent severe, influenza A/H3N2-dominated seasons, there were as many as 60,000 influenza-related deaths among persons over 65 years of age, and the majority of these were among persons aged 75 and older [2]. The current public health strategy for influenza is to reduce severe outcomes such as hospitalizations and deaths, by recommending annual vaccination for people at elevated risk for such outcomes, including all persons over the age of 65 [3]. Observational studies suggest that influenza vaccination is associated with enormous reductions in all winter mortality among the elderly [4] but such studies may Abbreviations: Ab, antibodies; GMT, geometric mean titre; HI, heam- agglutinin inhibition; OR, odds-ratio; CDC, Centers for Disease Control and Prevention; WHO, World Health Organization ∗ Corresponding author. Tel.: +1 301 402 8487; fax: +1 301 480 2954. E-mail address: lsimonsen@niaid.nih.gov (L. Simonsen). be subject to self-selection bias and overestimation of vac- cine benefits [2]. However, because immune responses in the elderly are known to be less vigorous than in younger adults, there has long been concern about whether the vaccine offers sufficient protection in this age group [5,6]. In 1989, Beyer et al. published a review of studies that compared antibody responses to influenza vaccination in the elderly to those of younger adults [7]. Of the 30 independent studies reviewed, the authors found that 10 reported a better immune response in the young, 4 reported a better response in the elderly, and 16 did not find a significant difference between the two groups. The authors concluded that several important factors, such as serious illnesses among study par- ticipants, use of medications that inhibit immune responses, previous influenza vaccination, and the presence of high pre- vaccination antibody titres, could not be controlled for in their review. They suggested that future studies exclude subjects for whom these factors exist. Since the 1989 review, several published studies have investigated the effects of these con- founding factors. 0264-410X/$ – see front matter © 2005 Elsevier Ltd. All rights reserved. doi:10.1016/j.vaccine.2005.08.105