Journal of Medical Virology 84:1274–1278 (2012) Persistence of Immunity to Tick-Borne Encephalitis After Vaccination and Natural Infection Tatjana Baldovin, 1 * Rosanna Mel, 2 Chiara Bertoncello, 1 Graziella Carpene `, 2 Fabio Soppelsa, 2 Aurore Giliberti, 1 and Vincenzo Baldo 1 1 Department of Molecular Medicine, Institute of Hygiene, University of Padua, Italy 2 Department of Public Health, Belluno, Italy Long-term persistence of immunity was assessed in 66 patients who had contracted tick-borne encephalitis (TBE) and in 126 subjects who had completed primary TBE im- munization using a conventional three-dose schedule from 3 to 8 years earlier. Immunity was tested in the subjects stratified by age as follows: 40 years (N ¼ 37); 41–60 years (N ¼ 100); and over 60 years (N ¼ 55). Antibody levels decreased significantly with increasing age in the vaccinated cohort by comparison with the individuals who had previously con- tracted TBE. Consistently higher geometric mean antibody levels were found in the patients infected naturally. When the vaccinat- ed subjects were compared, subjects 40 years old had significantly higher antibody levels than either of the older groups. Analyzing im- munity to TBE over time revealed a remarkable (50%) decline in seroprotection rates in the vac- cinated group at 50 months of follow-up, while stable, high levels persisted in all subjects after natural TBE infection. In the vaccinees over 60 years old, the TBE antibody levels reached 60% at 60 months, and 20% at 70 months of follow-up; in contrast, in the 41–60-year-old group, the antibody levels remained high for 70 months, and then fell rapidly. For people aged <60 years old, booster doses are recom- mended every 5 years after the fourth dose of vaccine, which should be administered 3 years after primary immunization. In subjects aged 60 years or older, booster doses should be giv- en every 3 years. J. Med. Virol. 84:1274– 1278, 2012. ß 2012 Wiley Periodicals, Inc. KEY WORDS: TBE; vaccine; immunity; booster INTRODUCTION Tick-borne encephalitis (TBE) is an acute human arboviral infection of the central nervous system caused by the TBE virus (TBEV), which belongs to the Flaviviridae family and is transmitted by the bite of an infected tick [Dumpis et al., 1999] or, much more rarely, it can be contracted by consuming unpasteurized dairy products from infected livestock [Holzmann et al., 2009; Su ¨ ss, 2011]. TBE is widespread not only in Europe, but also in many Asian regions. Risk areas are expanding and new foci are being discovered continually, even at higher altitudes [Bro ¨ker and Gniel, 2003; Kunze and ISW TBE, 2010; Kollaritsch et al., 2011]. TBE thus represents a growing public health concern in Europe as well as in other parts of the world. Most cases of TBE in Europe occur during the peri- od when ticks are most active, between April and No- vember, when the climatic conditions and habitat (meadows, forest with undergrowth) are most favor- able [Su ¨ ss, 2003; Lindquist and Vapalahti, 2008]. Lately, however, as a consequence of various environ- mental, social, economic, and demographic factors, there has been a steady increase in the spread of tick- borne diseases according to monthly reports. TBE- infections caused by the European subtype of these viruses typically take a biphasic course with a vari- able severity of neurological symptoms, particularly in the second phase [Holzmann, 2003; Donoso Mantke et al., 2008]. So, while the mortality rate in Europe is estimated to be about 1%, TBE may result in long- term neurological sequelae for 26–50% of patients, which are considered severe in about 10% of cases [Vene et al., 2007]. Although the resident populations are the most ex- posed to the risk of infection because of their involve- ment in rural activities and working environments, The authors have no conflict of interest to declare. *Correspondence to: Tatjana Baldovin, Department of Molecular Medicine, Institute of Hygiene Via Loredan 18, 35131 Padua, Italy. E-mail: tatjana.baldovin@unipd.it Accepted 27 March 2012 DOI 10.1002/jmv.23313 Published online in Wiley Online Library (wileyonlinelibrary.com). ß 2012 WILEY PERIODICALS, INC.