Elsevier Vaccine. Vol. 14, No. 14, pp. 1331-1339, 1996 Copyright 0 1996 Elsevier Science Ltd. All rights reserved Printed in Great Britain ELSEVIER PII: S0264410X(96)00058-8 0264-41 OX/96 $15+0.00 zyxwvutsrq Effects of repeated annual influenza vaccination on vaccine sero-response in young and elderly adults W.E.P. Beyer*, A.M. Palache*, M.J.W. Sprenger’f, E. HendriksenS, J.J. Tukkers, R. Dariolil, G.L. van der Water*, N. Masurel* and A.D.M.E. Osterhaus*ll zyxwvutsrqponmlkjihgfedcbaZYXWVUTSRQPONMLKJIHGFEDCBA Three cohort studies in adults were performed during the zyxwvutsrqponmlkjihgfedcbaZYXWVUTSRQPONMLKJIHGFE periode from 1986 to 1989. Eight hundred and eighty-four subjects were, one or more times, immunized with inf?uenzu vaccines, and pre- and post-vaccination antibody titres were determined by hemagglutina- tion inhibition tests. One thousand and one hundred and nineteen vaccination events in 681 subjects could be analysed by a comparison, per trial andper influenza (sub) type, between groups with and without influenza vaccination in previous years. Eflect size, odds ratio and protection rate deference, were used as e#ect measures. Subjects with previous vaccination showed higher pre-vaccination antibody than those without. The average change of the post-vaccination proportion of subjects with high antibody titre value to previous vaccination, was +9.4% (95% CI: +5.3 to 13.6%) for A-H3N2 vaccine components, -2.1% (-8.1 to 3.9%, not significant) for A-HlNl and -10.6% (-16.5% to -4.8%) for B. In a linear regression model, pre-vaccination titres and the status of previous vaccination were identified as factors signt$cantly influencing post-vaccination titres. These findings are discussed in the context of a short review of the literature. It is concluded that the status of previous vaccination should always be addressed as an independent factor in serological vaccination studies. Copyright 0 1996 Elsevier Science Ltd. Keywords: Icfluenza vaccine; hemagglutination inhibition test; vaccine sero response; repeated vaccination Active immunization with inactivated vaccines against influenza virus types A and B in subjects at risk of developing serious complications after influenza infec- tion, has been advised to be repeated annually to comply with antigenic drift of the viruses and decrease of antibody levels with time. This policy, however, has been questioned by field studies in the 197Os, which suggested a decrease of protective immunity upon annually re- peated vaccination’-3. Although the methods of these studies have been criticized4 and more recent studies5-7 have not confirmed these findings, the value of annual influenza vaccination still remains a subject of discussion. *WHO National Influenza Centre, Institute of Virology, Erasmus University Rotterdam, P.O. Box 1738, 3000 DR Rotterdam, The Netherlands. TDepartment of Infectious Diseases and Epidemiology, National Institute of Public Health and Environmental Protection, Bilthoven, The Netherlands. SNursing Home Den Ooiman, Doetinchem, The Netherlands. $Department of Pharmacy, University of Utrecht, Utrecht, The Netherlands. IDepartment of Internal Medicine, University of Lausanne, Lausanne, Switzerland. IiTo whom correspondence should be addressed. (Received 7 April 1995; accepted 26 February 1996) Field vaccination studies are difficult to perform due to the poor predictability of influenza outbreaks, which makes power-calculations troublesome. The most important parameters of efficacy are reduction of mortality and severe morbidity which may not occur frequently thus requiring large numbers of participants in efficacy trials. Moreover, since a beneficial effect of influenza vaccination has been established, it is no longer ethically acceptable to perform double-blind, prospective field studies in groups at risk of developing serious complications. Therefore. serological studies with hemagglutination inhibition (HI) serum antibody titres as a surrogate marker for real vaccine efficacy, are usually performed, with divergent results: some- times a lower7.‘, and sometimes a higher’ post- vaccination serum antibody titre was observed in subjects with a vaccination history when compared to those not vaccinated before, and in other studies, post-vaccination antibody titres were not significantly affected by previous vaccinationss,‘0-‘7. Here we present the results of three different cohort studies, performed in primed populations during an inter-pandemic period (19861989) with low activity of naturally occurring influenza. Vaccine 1996 Volume 14 Number 14 1331