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J. cells were still present and higher levels of pertussis-specific antibodies than prebooster were found in aP-primed children and, to a lesser degree, also in wP-primed children. The antibodies consisted mainly of the IgG1 subclass but also showed an increased IgG4 portion, primarily in the aP-primed children. The antibody avidity indices for pertussis toxin and pertactin in aP-primed children were already high prebooster and remained stable at Nifurtimox 2 years, whereas those in wP-primed children increased. All measured prebooster T-cell responses in aP-primed children Nifurtimox were already high and remained at similar levels or even decreased during the 2 years after booster vaccination, whereas those in wP-primed children increased. Since the Dutch wP vaccine has been replaced by aP Nifurtimox vaccines, the induction of B-cell and T-cell memory immune responses has been enhanced, but antibody levels still wane after five aP vaccinations. Based on these long-term immune responses, the Dutch pertussis vaccination routine can be optimized, and we discuss here several options. INTRODUCTION Despite high rates of vaccination protection in young children since the 1940s and 1950s, whooping cough is usually reemerging in high-income countries. In the Netherlands, this reemergence was noticed from 1996 onward. Since then, peak incidences were observed every 2 to 3 3 years, which were most obvious in children 4 to 5 years of age who had been vaccinated with whole-cell pertussis (wP) vaccine at 2, 3, 4, and 11 months of age (1). However, the vaccine efficacy of the Dutch wP vaccine was not optimal, due to low concentrations of and low antibody responses to pertussis toxin (PT), filamentous hemagglutinin (FHA), and pertactin (Prn) (2C4). Therefore, in 2001 an acellular pertussis (aP) preschool booster vaccination at 4 years of age was implemented, which Rabbit polyclonal to ARHGAP15 shifted the age of the highest pertussis incidence toward 9 years of age (5). From 2005 onward, all main wP vaccinations have been replaced by aP vaccinations. However, despite the implementation of aP vaccinations in the industrialized world since the 1990s, the pertussis reemergence has not been halted. In 2012, a new pertussis incidence peak in the Netherlands was observed in adolescents and adults, who can infect newborns who have not been fully vaccinated, with high risks of severe disease and even death. The immune mechanisms important for protection against pertussis in humans remain elusive. Protection against pertussis is probably multifactorial (6) and is suggested to be mediated by both humoral (7, 8) and cell-mediated (9C13) immunity. High levels of antibodies against pertussis show previous contamination or recent vaccination and probably are associated with protection against pertussis (8, 14). In general, higher antibody levels have been observed after switching from wP to aP vaccinations (3, 15). These antibody responses consist of different subclasses with IgG1 as the dominant subtype, followed by IgG2, IgG3, and IgG4 (16). The induction of IgG subclasses is usually regulated by T-cell cytokine production and is influenced by the nature and dose of the vaccine antigens as well as the age of the vaccinees (17). Previously higher memory B-cell responses and greater avidity of pertussis-specific antibodies in aP-primed children than in wP-primed children at 4 years of age were reported (2, 18), indicating a more robust humoral immune response over time after infant vaccination with aP vaccines. Additionally, aP vaccination induced higher Th1 and Th2 T-cell responses 3 years after the main vaccination series than did wP vaccination (19). For optimal vaccination strategies, it is important to evaluate the longevity of the pertussis-specific immune response. The aim of this study is usually to evaluate the long-term antibody production and memory B-cell and T-cell immune responses in children 6 years of age, 2 years after aP preschool booster vaccination. The children experienced previously been vaccinated during infancy with either the Dutch wP vaccine or an aP vaccine. MATERIALS AND METHODS Study populace. The children explained in this study represent a subset from a larger cross-sectional study (registered trial no. ISRCTN65428640), performed between 2007 and 2009 in the Netherlands, that investigated the immunity to in children 3 to 9 years of age. In this study, single blood samples (8 to 15 ml) were collected by venipuncture in two groups of wP-primed children 4 years of age (prebooster, = 61; 28 days postbooster, = 52), one group of wP-primed children 6 years of age (2 years postbooster, = 63), and three corresponding groups of aP-primed children 4 and 6 years of age (prebooster, = 61; 28.