Vaccine 26 (2008) 3903–3908 Contents lists available at ScienceDirect Vaccine journal homepage: www.elsevier.com/locate/vaccine Predicted long-term persistence of pertussis antibodies in adolescents after an adolescent and adult formulation combined tetanus, diphtheria, and 5-component acellular pertussis vaccine, based on mathematical modeling and 5-year observed data F. Bailleux a , L. Coudeville a , A. Kolenc-Saban b , J. Bevilacqua b , L. Barreto b , P. Andr´ e a,∗ a Sanofi Pasteur Sa, 2 avenue Pont Pasteur, F-69367 Lyon cedex 07, France b Sanofi Pasteur Limited, 1755 Steeles Avenue West, Toronto, Ontario M2R 3T4, Canada article info Article history: Received 10 December 2007 Received in revised form 21 April 2008 Accepted 28 April 2008 Available online 2 June 2008 Keywords: Pertussis antibodies decay Linear regression Adolescents Booster administration abstract In a clinical trial, adolescents who had received a booster dose of reduced dose diphtheria–tetanus-5- component acellular pertussis vaccine (Adacel ® , Tdap) 5 years earlier maintained increased antibody concentrations to all antigens compared with pre-vaccination values. Observed data were applied to several mathematical models designed to predict further antibody decay for pertussis antigens. A linear mixed model including a random-intercept term provided the best fit for the observed data and was used for predictions. The predicted times for sufficient antibody decay to reach pre-vaccination levels were 15.3 years (95% CI: 7.0–28.0) for pertactin, 11.0 years (5.7–18.9) for fimbriae types 2 and 3, 10.5 years (3.6–24.7) for pertussis toxoid and 9.5 years (4.2–24.6) for filamentous hemagglutinin. For at least 87% of subjects, the 10-year predicted antibody concentration was higher than the limit of quantitation (LOQ) for each pertussis antigen measured. These results support Tdap booster doses every 10 years, following the current schedule for Td vaccination. © 2008 Elsevier Ltd. All rights reserved. 1. Introduction Pertussis continues to be a public health problem despite widespread childhood immunization. An increase in reported cases in many countries has been associated with a shift in the age distribution toward infants too young to be vaccinated and older persons with waning immunity [1–3]. In United States, 64% of reported cases occurred in adolescents or adults in 2003, and reports increased subsequently [4,5]. The adolescent and adult population represents an important source of transmission to sus- ceptible infants [6–8]. It has been suggested that immunization of adolescent and adult populations could indirectly protect very young infants by eliminating an important reservoir of disease [9]. Recently, adolescent/adult formulation combination vaccines containing tetanus toxoid with reduced amounts of the diphtheria and acellular pertussis antigens (Tdap) have been developed and licensed. Current recommendations for Td vaccines are for revacci- nation every 10 years [10]. Further information on the duration of ∗ Corresponding author. Tel.: +33 4 37 37 72 73; fax: +33 4 37 37 70 44. E-mail address: philippe.andre@sanofipasteur.com (P. Andr´ e). protection associated with the pertussis components of new vac- cines is therefore necessary. A small but growing set of data on the persistence of immuniza- tion after booster in adolescents and in adults with these vaccines presents data for up to 3 years [11–13] or 5 years [14]. Immunity induced after three doses of acellular or whole cell pertussis vaccine in the first year of life declines rapidly to low levels within 1 year [15–18]. Immune responses induced by natural infection also show an initial rapid increase, followed by a slow decline over a longer period of time [19–21]. In adults, the antibody decay patterns after booster immunization [22,23] and after natural infection are quite similar to those in adolescents [21]. We applied data gathered from a 5-year follow-up study of a Tdap vaccine in adolescents [24] to develop a mathematical model to predict the long-term antibody persistence to the pertussis antigens after booster vaccination with Tdap for up to 20 years. 2. Materials and methods 2.1. Study design Antibody data in adolescents obtained during a follow-up study of humoral immunity at 1, 3 and 5 years after receiving a booster 0264-410X/$ – see front matter © 2008 Elsevier Ltd. All rights reserved. doi:10.1016/j.vaccine.2008.04.089