Pertussis vaccinations in Dutch children: memory immune responses

Abstract

Despite high pertussis vaccination coverage, pertussis is reemerging in the Netherlands since 1996. In attempt to improve protection against whooping cough, two major changes in the national immunization program have been made; the introduction of a preschool booster vaccination in children 4 years of age in 2001 and the replacement of the whole-cell pertussis (wP) vaccine with an acellular pertussis (aP) vaccine at 2, 3, 4 and 11 months of age since 2005. Despite these changes, pertussis is still reemerging, although the incidence has shifted to adolescents and adults. In this thesis we studied the effect of primary wP and aP vaccinations on the long-term memory immune responses against pertussis in groups of children between 3 and 9 years of age. We showed a superior memory immune response in children after aP vaccinations compared with children after wP vaccinations. However, in children 4 years of age an overstimulation of the immune system seemed to occur after the fifth high-dose aP vaccination. In wP primed children a high-dose aP booster at 4 years of age induced superior memory immune responses as compared to a low-dose aP vaccine and an extra aP booster vaccination at 9 years of age even further improved the pertussis-specific memory immune responses. Moreover, we showed an additional role for serum IgA antibodies against pertussis toxin in pertussis diagnostics in the vaccinated population. The findings in this thesis demonstrate the additional value of the investigation of pertussis-specific memory B- and T-cell immune responses that represent long-term immunity when antibodies have waned. We show that memory B-cell responses next to antibody responses will probably be involved in the reduction of pertussis disease after vaccination in children. We support that aP vaccines have improved protection against pertussis in children. However, further investigation to an optimal pertussis vaccination program with aP vaccines has to be done. Memory B- and T-cell responses provide more information of the immunological mechanisms of protection induced by pertussis vaccinations. Therefore, memory immune responses offer further hallmarks for the optimalization of pertussis vaccination strategies.